Archives of Dermatology

lijima, Shigeruko;Saito, Junko;Otsuka, Fujio

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440013001

Abstract REPORT OF A CASE A 30-year-old Japanese man first noticed a small, slightly pruritic nodule on the dorsum of his left hand in December 1993. Before the patient presented to us in May 1994 he was treated by his personal physician, who prescribed several antibiotics for 2 months without apparent response. The nodule slowly grew and became tender. Another small nodule then appeared on his left forearm. The patient had kept tropical fish for 5 years and he reported injuring his left hand when cleaning the fish tank.A physical examination revealed 2 dark, erythematous, and slightly elevated nodules that measured 37×17 mm on the dorsum of his left hand and 47×25 mm on his forearm (Figure 1). Both nodules were exudative and purulent. The superficial regional lymph nodes were not swollen.Results of the laboratory examination, which included a complete blood cell count with differentiation, blood chemistry profile, and References 1. Edelstein H. Mycobacterium marinum skin infections: report of 31 cases and review of the literature . Arch Intern Med. 1994;154:1359-1364.Crossref 2. Kullavanijaya P, Sirimachan S, Bhuddhavudhikrai P. Mycobacterium marinum cutaneous infections acquired from occupations and hobbies . Int J Dermatol. 1993;32:504-507.Crossref 3. Donta ST, Smith PW, Levitz RE, Quintiliani R. Therapy of Mycobacterium marinum infections: use of tetracyclines vs rifampin . Arch Intern Med. 1986;146: 902-904.Crossref 4. Sanders WJ, Wolinsky E. In vitro susceptibility of Mycobacterium marinum to eight antimicrobial agents . Antimicrob Agents Chemother. 1980;18:529-531.Crossref 5. Arai H, Nakajima H, Kaminaga Y. In vitro susceptibility of Mycobacterium marinum to dihydromycoplanecin A and ten other antimicrobial agents . J Dermatol. 1990;17:370-374. 6. Brown BA, Wallace RJ Jr, Onyi GO. Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system . Antimicrob Agents Chemother. 1992;36:1987-1990.Crossref 7. Kuhn SM, Rosen W, Wong A, Jadavji T. Treatment of Mycobacterium marinum facial abscess using clarithromycin . Pediatr Infect Dis J. 1995;14:631-632.Crossref 8. Leysen DC, Haemers A, Pattyn SR. Mycobacteria and the new quinolones . Antimicrob Agents Chemother . 1989;33:1-5.Crossref 9. Garcia-Rodriguez JA, Gomez Garcia AC. In-vitro activities of quinolones against mycobacteria . J Antimicrob Chemother. 1993;32:797-808.Crossref 10. Tomioka H, Sato K, Saito H. Comparative in vitro and in vivo activity of fleroxacin and ofloxacin against various mycobacteria . Tubercle. 1991;72:176-180.Crossref 11. Saito H, Tomioka H, Sato K, Dekio S. In vitro and in vivo antimycobacterial activities of a new quinolone, DU-6859a . Antimicrob Agents Chemother. 1994;38: 2877-2882.Crossref 12. Ishida M, Takei A, Itoh M, Tsuyuki S, Yamaguchi K. A case of atypical Mycobacterium infection [in Japanese] . Jpn J Dermatol. 1993;103:860. Abstract. 13. Arai H, lemoto G, Nakajima H, Kaminaga Y. A case of Mycobacterium marinum skin infection [in Japanese] . Hifubyoh-shinryoh. 1995;17:379-382. 14. Une T, Fujimoto T, Sato K, Osada Y. In vitro activity of DR-3355, an optically active ofloxacin . Antimicrob Agents Chemother. 1988;32:1336-1340.Crossref 15. Fujimoto T, Mitsuhashi S. In vitro antibacterial activity of DR-3355, the S-(-)— isomer of ofloxacin . Chemotherapy . 1990;36:268-276.Crossref 16. Tanaka M, Otsuki M, Une T, Mshino T. In vitro and in vivo activity of DR-3355, an optically active isomer of ofloxacin . J Antimicrob Chemother. 1990;26:659-666.Crossref 17. Takahashi H, Mogi S, Kobayashi M, et al. Assay of skin level and clinical investigation of levofloxacin in the treatment of skin infections [in Japanese] . Chemotherapy . 1992;40( (S-3) ):286-305. 18. Nakashima M, Uematsu T, Kanamaru M, Okazaki O, Hakusui H. Phase 1 study of levofloxacin, S—(-)-ofloxacin . Jpn J Clin Pharmacol Ther. 1992;23:515-520.Crossref

Weinstock, Martin A.;Barnhill, Raymond L.;Rhodes, Arthur R.;Brodsky, Gilbert L.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440019002

Abstract Objective: To determine the reliability of the histopathologic diagnosis of melanocytic dysplasia among diverse dermatopathologists who had no joint training, agreed to abide by predetermined criteria, and who were provided reference photomicrographs illustrative of the criteria. Design, Setting, and Participants: A stratified random sample of 112 melanocytic tumors were chosen from the files of the pathology department of a large staff-model health maintenance organization. The original diagnoses included typical and dysplastic melanocytic nevi and melanoma. A single representative slide for each case was interpreted independently by each of the 5 panel dermatopathologists and 2 melanoma specialists. They had no prior knowledge of the original diagnosis or the diagnoses of the other panel members. Interventions: None. Main Outcome Measures: Interrater reliability was measured by intraclass and Pearson correlation coefficients. Each case was graded on a 5-point scale from no dysplasia to melanoma. Results: The intraclass correlation among the panel members was 0.67 (95% confidence interval, 0.59-0.73). The Pearson correlations of each of the 5 panel dermatopathologists with the mean of the 2 melanoma specialists ranged from 0.67 to 0.84, and the correlations of the mean of the panel with the 2 melanoma specialists were 0.79 and 0.82; the mean reading of the melanoma specialists correlated 0.89 with the mean panel reading. Apparent protocol violations occurred in 6.5% of the readings. Conclusions: Agreement was substantial to excellent for the histopathologic diagnosis of 112 melanocytic tumors by dermatopathologists. Using predetermined criteria, melanocytic dysplasia can be reproducibly graded among diverse general dermatopathologists.Arch Dermatol. 1997;133:953-958 References 1. Weinstock MA. Dysplastic nevi revisited . J Am Acad Dermatol. 1994;30:807-810.Crossref 2. Roth ME, Grant-Kels JM, Ackerman AB, et al. The histopathology of dysplastic nevi: continued controversy . Am J Dermatopathol. 1991;13:38-51.Crossref 3. Rhodes AR, Mihm MC Jr, Weinstock MA. Dysplastic melanocytic nevi: a reproducible histologic definition emphasizing cellular morphology . Mod Pathol. 1989; 2:306-319. 4. Clemente C, Cochran AJ, Elder DE, et al. Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme . Hum Pathol. 1991;22:313-319.Crossref 5. Piepkorn MW, Barnhill RL, Cannon-Albright LA, et al. A multi-observer, population-based analysis of histologic dysplasia in melanocytic nevi . J Am Acad Dermatol. 1994;30:707-714.Crossref 6. Zar JH. Biostatistical Analysis. 2nd ed. Englewood Cliffs, NJ: Prentice-Hall International Inc; 1984. 7. Agresti A. Analysis of Ordinal Categorical Data . New York, NY: John Wiley & Sons Inc; 1984. 8. Brennan P, Silman A. Statistical methods for assessing observer variability in clinical measures . BMJ . 1992;304:1491-1494.Crossref 9. Cohen J. Weighted kappa: nominal scale agreement with provision for scaled disagreement or partial credit . Psychol Bull. 1968;70:213-220.Crossref 10. Fleiss JL, Cohen J. The equivalence of weighted kappa and the intraclass correlation coefficient as measures of reliability . Educ Psychol Meas. 1973;33:613-619.Crossref 11. Maclure M, Willett WC. Misinterpretation and misuse of the kappa statistic . Am J Epidemiol. 1987;126:161-169.Crossref 12. Byrt T, Bishop J, Carlin JB. Bias, prevalence, and kappa . J Clin Epidemiol. 1993; 46:423-429.Crossref 13. Graham P, Jackson R. The analysis of ordinal agreement data: beyond weighted kappa . J Clin Epidemiol. 1993;46:1055-1062.Crossref 14. Sagebiel RW, Banda PW, Schneider JS, Crutcher WA. Age distribution and histologic patterns of dysplastic nevi . J Am Acad Dermatol. 1985;13:975-982.Crossref 15. Heenan PJ, Matz LR, Blackwell JB, et al. Inter-observer variation between pathologists in the classification of cutaneous malignant melanoma in Western Australia . Histopathology. 1984;8:717-729.Crossref 16. Colloby PS, West KP, Fletcher A. Observer variation in the measurement of Breslow depth and Clark's level in thin cutaneous malignant melanoma . J Pathol. 1991; 163:245-250.Crossref 17. Walter SD, Marrett LD, Hertzman C. Reliability of interviewer and subject assessments of nevus counts in a study of melanoma . J Clin Epidemiol. 1991;44: 633-640.Crossref 18. Leffell DJ, Chen Y-T, Berwick M, Bolognia JL. Interobserver agreement in a community skin cancer screening setting . J Am Acad Dermatol. 1993;28:1003-1005.Crossref 19. Carli P, Urso C, De Giorgi V, Biggeri A, Bondi R, Giannottii B. Sensitivity and specificity of clinical criteria in the detection of histologic atypia in nevi . Eur J Dermatol. 1994;4:35-39. 20. de Vet HCW, Knipschild PG, Schouten HJA, et al. Interobserver variation in histopathological grading of cervical dysplasia . J Clin Epidemiol. 1990;43:1395-1398.Crossref 21. Stanganelli I, Burroni M, Rafanelli S, Bucchi L. Intraobserver agreement in interpretation of digital epiluminescence microscopy . J Am Acad Dermatol. 1995; 33:584-589.Crossref 22. Whited JD, Horner RD, Hall RP, Simel DL. The influence of history on interobserver agreement for diagnosing actinic keratoses and malignant skin lesions . J Am Acad Dermatol. 1995;33:603-607.Crossref 23. Meyer LJ, Piepkorn M, Goldgar DE, et al. Interobserver concordance in discriminating clinical atypia of melanocytic nevi, and correlations with histologic atypia . J Am Acad Dermatol. 1996;34:618-625.Crossref 24. Lock-Andersen J, Hou-Jensen K, Hansen JPH, Jensen NK, Sogaard H, Andersen PK. Observer variation in histological classification of cutaneous malignant melanoma . Scand J Plast Reconstr Hand Surg. 1995;29:141-148.Crossref 25. Schmoeckel C. How consistent are dermatopathologists in reading early malignant melanomas and lesions 'precursor' to them? an international survey . Am J Dermatopathol. 1984;6( (suppl) ):13-24. 26. Krieger N, Hiatt RA, Sagebiel RW, Clark WH, Mihm MC. Inter-observer variability among pathologists' evaluation of malignant melanoma: effect upon an analytic study . J Clin Epidemiol. 1994;47:897-902.Crossref 27. Corona R, Mele A, Amini M, et al. Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions . J Clin Oncol. 1996;14:1218-1223. 28. Duray PH, DerSimonian R, Barnhill RL, et al. An analysis of interobserver recognition of the histopathologic features of dysplastic nevi from a mixed group of nevomelanocytic lesions . J Am Acad Dermatol. 1992;27:741-749.Crossref 29. Duncan LM, Berwick M, Bruijn JA, Byers HR, Mihm MC, Barnhill RL. Histopathologic recognition and grading of dysplastic melanocytic nevi: an interobserver agreement study . J Invest Dermatol. 1993;100( (suppl) ):318S-321S.Crossref 30. Ahmed I, Peipkorn MW, Rabkin MS, et al. Histopathologic characteristics of dysplastic nevi: limited association of conventional histologic criteria with melanoma risk group . J Am Acad Dermatol. 1990;22:727-733.Crossref 31. de Wit PEJ, van't Hof-Grootenboer B, Ruiter DJ, et al. Validity of the histopathological criteria used for diagnosing dysplastic naevi: an interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group . Eur J Cancer. 1993;29A:831-839.Crossref 32. Hastrup N, Clemmensen OJ, Spaun E, Sondergaard K. Dysplastic naevus: histologic criteria and their inter-observer reproducibility . Histopathology. 1994; 24:503-509.Crossref

Horn, Thomas D.;Zahurak, Marianna L.;Atkins, Debra;Solomon, Alvin R.;Vogelsang, Georgia B.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440027003

Abstract Background: The discrimination between acute and chronic graft-vs-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) is important because the treatment regimens and prognosis differ. Objectives: To identify whether accepted histopathologic criteria of a graft-vs-host reaction (GVHR) alone or in combination accurately reflect clinical phase of disease, to correlate patterns with clinical outcome, and to identify any concordance between inflammation and epidermal changes of a GVHR. Design: Skin biopsy specimens were analyzed according to histologically defined standards. Settings: This study was performed in a tertiary care hospital. Patients: One hundred seventy-three skin biopsy specimens (10 days before to 1326 days after BMT) from 83 patients undergoing allogeneic BMT for various malignant neoplasms were selected for study. A consecutive 12-month sample was used. Main Outcome Measures: The main measures in this study were statistical correlations between histopathologic findings and time after BMT, the outcome of BMT, and the correlations between selected histopathologic criteria. Results: Fully evolved histologic features of chronic lichenoid GVHR in the specimens occurred across a wide time range (33-832 days after BMT) and were associated with a 5.6-fold increased risk for death (P=.02) from GVHD. Histologic features of acute GVHR in the specimens also occurred across a wide time range (14-481 days after BMT) and were associated with a 2.2-fold increased risk for death; this finding was not statistically significant (P=.11). Inflammation of the upper dermis was significantly associated with acanthosis and epidermal cell necrosis (P<.001 and P<.001, respectively, for bandlike pattern), confirming the importance of this finding as a criterion for the diagnosis of a GVHR. Blinded evaluation of a subset of specimens for the diagnosis of acute vs chronic GVHR resulted in wide interobserver variation. Conclusions: This study demonstrates the following: specific histologic parameters in skin biopsy specimens do not consistently separate acute from chronic GVHD as defined by days after BMT; independent of time course, fully evolved histopathologic characteristics of a lichen planus—like GVHR is associated with a greater likelihood of death from GVHD; and identification of upper dermal inflammation correlates with the epidermal features of GVHR and should be included in the diagnostic scheme.Arch Dermatol. 1997;133:961-965 References 1. Horn TD. Graft-versus-host disease . In: Arndt KA, LeBoit PE, Robinson JK, Wintroub BU, eds. Cutaneous Medicine and Surgery . Philadelphia, Pa: WB Saunders Co; 1996:225-234. 2. Snover DC. Acute and chronic graft versus host disease: histopathological evidence for two distinct pathogenetic mechanisms . Hum Pathol. 1984;15:202-205.Crossref 3. Farmer ER. Human cutaneous graft-versus-host disease . J Invest Dermatol. 1985; 85( (suppl) ):124S-128S.Crossref 4. Lerner KG, Kao GF, Storb R, et al. Histology of graft-versus-host reaction (GvHR) in human recipients of marrow from HLA-matched sibling donors . Transplantation. 1974;4:367-371. 5. Saurat JH, Gluckman E, Bussel A, et al. The lichen planuslike eruption after bone marrow transplantation . Br J Dermatol. 1975;93:675-681.Crossref 6. Weiden PL, Sullivan K, Flournoy N, et al. Anti-leukemic efect of chronic graft-versus-host disease: contribution to improved survival after allogeneic bone marrow transplantation . N Engl J Med. 1981;304:1529-1533.Crossref 7. Darmstadt GL, Donnenberg AD, Vogelsang GB, Farmer ER, Horn TD. Clinical, laboratory, and histopathologic indicators of the development of progressive acute graft-versus-host disease . J Invest Dermatol. 1992;99:397-402.Crossref 8. Horn TD, Bauer DJ, Vogelsang GB, Hess AD. Reappraisal of histologic features of the acute cutaneous graft-versus-host reaction based upon an allogeneic rodent model . J Invest Dermatol. 1994;103:206-210.Crossref 9. Cox DR. The Analysis of Binary Data . London, England: Meuthen; 1970. 10. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models . Biometrika . 1986;73:13-22.Crossref 11. Zeger SL, Liang KY, Albert PS. Models for longitudinal data: a generalized estimating equation approach . Biometrics. 1988;44:1049-1060.Crossref 12. Wingard JR, Piantadosi S, Vogelsang GB, et al. Predictors of death from chronic graft-versus-host disease after bone marrow transplantation . Blood. 1989;74: 1428-1435.

Jemec, Gregor B. E.;Gniadecka, Monika

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440033004

Abstract Objective: To describe the in vivo skin echostructure, hair follicle shape, and dermal thickness in hidradenitis suppurativa. Design: Qualitative and quantitative assessment of highfrequency (20-MHz) B-mode ultrasound images of lesional and paralesional skin. Setting: University hospital. Patients: Age- and sex-matched outpatients with hidradenitis suppurativa (n=15) and healthy control subjects (n=13). Median age was 34 years (range, 31-38). Results: Clinically normal paralesional hair follicles in hidradenitis have an abnormal shape. The follicles appear to be wider in the deep dermis, the difference being statistically significant in the genitofemoral region (P=.007). Patients with hidradenitis have larger follicles in the axilla than controls (P=.002). Mature acne and hidradenitis lesions are indistinguishable, but both are different from epidermal cysts. Mean axillary and genitofemoral skin was significantly thicker in patients than in controls. Conclusions: In vivo ultrasonography shows characteristic differences in the shape of hair follicles in hidradenitis. The general underlying abnormalities appear to occur in the deep part of the follicle. The mature lesions are indistinguishable from acne, but are clearly different from epidermal cysts. A thickened skin may play a pathogenic role in the development of hidradenitis.Arch Dermatol. 1997;133:967-970 References 1. Rodder Wehrmann O, Kuster W, Plewig G. Acne inversa: diagnosis and therapy [in German] . Hautarzt. 1991;42:5-8. 2. Jemec GB, Hansen U. Histology of hidradenitis suppurativa . J Am Acad Dermatol. 1996;34:994-999.Crossref 3. Ramasastry SS, Conklin WT, Granick MS, Futrell JW. Surgical management of massive perianal hidradenitis suppurativa . Ann Plast Surg. 1985;15:218-223.Crossref 4. Jemec GB. Effect of localized surgical excisions in hidradenitis suppurativa . J Am Acad Dermatol. 1988;18:1103-1107.Crossref 5. Alexander H, Miller D. Determining skin thickness with pulsed ultrasound . J Invest Dermatol. 1979;72:17-19.Crossref 6. Serup J, Keiding J, Fullerton A, et al. High-frequency ultrasound examination of skin: introduction and guide . In: Serup J, Jemec G, eds. Handbook of Noninvasive Methods and the Skin . Boca Raton, Fla: CRC Press Inc; 1995:239-256. 7. Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial benign pemphigus: surgical approach . In: Roenigk RK, Roenigk HH Jr, eds. Dermatologic Surgery . New York, NY: Marcel Dekker Inc; 1989:717-743. 8. Burke BM, Cunliffe WJ. The assessment of acne vulgaris: the Leeds technique . Br J Dermatol. 1984;111:83-92.Crossref 9. Gniadecka M, Gniadecki R, Serup J, Sondergaard J. Ultrasound structure and digital image analysis of the subepidermal low echogenic band in aged human skin: diurnal changes and intraindividual variability . J Invest Dermatol. 1994; 102:362-365.Crossref 10. Gniadecka M, Serup J, Sondergaard J. Age-related changes of skin oedema by high-frequency ultrasound . Br J Dermatol. 1995;131:849-855.Crossref 11. Jansen T, Plewig G. Classification of suppurative hidradenitis [in German] . Hautarzt. 1994;45:652-653.Crossref 12. Attanoos RL, Appleton MA, Douglas Jones AG. The pathogenesis of hidradenitis suppurativa: a closer look at apocrine and apoeccrine glands . Br J Dermatol. 1995;133:254-258.Crossref 13. Gniadecka M, Omskeff B. Assessment of dermal water by high-frequency ultrasound: comparative studies with nuclear magnetic resonance . Br J Dermatol. 1996;135:218-224.Crossref 14. Serup J, Staberg B. Ultrasound for assessment of allergic and irritant patch test reactions . Contact Dermatitis. 1987;17:80-84.Crossref 15. de Rigal J, Escoffier C, Querleux B, Faivre B, Agache P, Leveque J. Assessment of ageing of the human skin in vivo: ultrasound imaging . J Invest Dermatol. 1989; 93:621-625.Crossref 16. Gniadecka M, Danielsen L. High-frequency ultrasound for torture-inflicted skin lesions . Acta Derm Venerol (Stockh) . 1995;75:375-376. 17. Harrison BJ, Mudge M, Hughes LE. Recurrence after surgical treatment of hidradenitis suppurativa . BMJ. 1987;294:487-489.Crossref 18. Priesack W, Maroske D, Hamelmann H. Results of multiple surgical therapy in pronounced acne conglobata [in German] . Chirurg. 1984;55:343-346. 19. Overgaard Olsen L, Takiwaki H, Serup J. High-frequency ultrasound characterization of normal skin: skin thickness and echographic density of 22 anatomical sites . Skin Res Technol. 1995;1:74-81.Crossref

Plewig, Gerd

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440036005

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables. Abstract Ultrasound examination of the skin is becoming more and more important in dermatology. The use of noninvasive 20-MHz sonography is a well-established procedure in dermatology. It can be used to determine tumor thickness in malignant melanoma and basal cell carcinoma before treatment. The use of 20-MHz sonography permits the determination of skin thickness and density in patients with scleroderma and other connective tissue diseases. A reproducible evaluation of the effects of drugs on the skin is possible. In this article, Jemec and Gniadecka describe a new indication for using 20-MHz sonography in the diagnosis of hidradenitis suppurativa, a variant form of acne.

Sigler, Catherine;Annis, Karen;Cooper, Kevin;Haber, Harry;Van deCarr, Stephen

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440040006

Abstract Objective: To determine if mean levels of complement components and carboxypeptidase N differed when comparing patients who exhibited angioedema following angiotensin-converting enzyme inhibitor therapy to those who received angiotensin-converting enzyme inhibitor therapy but did not have angioedema. Design: Case-control study nested within an 8-week, open-label study of the use of quinapril hydrochloride for hypertension in 12 275 patients. Setting: Multicenter, with sites throughout the United States. Patients: Of the 36 patients with angioedema described, 22 participated in the study. They were matched to 48 controls by age, sex, race, length of follow-up, and geographical region. Intervention: All patients received quinapril therapy prior to participation in this case-control study. Main Outcome Measures: Levels of carboxypeptidase N, total hemolytic complement, Cl esterase inhibitor, and C4, along with questionnaire data, including a history of angioedema-like episodes and family history of angioedema. Results: The 22 patients had significantly lower mean levels of carboxypeptidase N (kininase I) (P=.03) and Cl esterase inhibitor (P=.04) compared with the 48 matched controls, but all mean values were within normal laboratory ranges. A history of prior angioedema-like episodes was associated with an approximate 6-fold increase in the subsequent risk of angioedema following angiotensin-converting enzyme inhibitor therapy. Conclusions: Small differences in levels of carboxypeptidase N or Cl esterase inhibitor may contribute to an increased risk of angioedema with angiotensinconverting enzyme inhibitor therapy. Given the large overlap in the distributions of carboxypeptidase N and Cl esterase inhibitor levels, prior testing could not be used to evaluate angioedema risk for an individual patient considering angiotensin-converting enzyme inhibitor therapy. A history of prior angioedema-like episodes was associated with increased risk, but this result should be interpreted with caution because of possible recall bias.Arch Dermatol. 1997;133:972-975 References 1. Slater EE, Merrill DD, Guess HA, et al. Clinical profile of angioedema associated with angiotensin-converting enzyme inhibition . JAMA. 1988;260:967-970.Crossref 2. Physician's Desk Reference. 49th ed. Montvale, NJ: Medical Economics Data Production Co; 1995:710, 724, 887, 1124, 1618, 1650, 1814, 2448. 3. McEvoy GK, ed. American Hospital Formulary Service Drug Information . Bethesda, Md: American Society of Health System Pharmacists; 1994:1201. 4. Singer DR, Macgregor GA. Angioneurotic oedema associated with two angiotensin converting enzyme inhibitors . BMJ. 1986;293:1243.Crossref 5. Wood SM, Mann RD, Rawlins MD. Angio-oedema and urticaria associated with angiotensin converting enzyme inhibitors . BMJ. 1987;294:91-92.Crossref 6. Mathews KP, Pan PM, Gardner NJ, Hugli TE. Familial carboxypeptidase N deficiency . Ann Intern Med. 1980;93:443-445.Crossref 7. Bokisch VA, Muller-Eberhard HJ. Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase . J Clin Invest. 1970;49: 2427-2436.Crossref 8. Erdos EG. Conversion of angiotensin I to angiotensin II . Am J Med. 1976;60: 749-759.Crossref 9. Erdos EG. Bradykinin, Kallidin, and Kallikrein: Handbook of Experimental Pharmacology . Berlin, Germany: Springer-Verlag; 1979:427-487. 10. Yang HY, Erdos EG. Second kininase in human blood plasma . Nature. 1967;215: 1402-1403.Crossref 11. Yang HY, Erdos EG, Levin Y. Characterization of a dipeptide hydrolase (kininase II: angiotensin I converting enzyme) . J PharmacolExp Ther. 1971;177:291-300. 12. Landerman NS, Webster ME, Becker EL, Ratcliffe HE. Hereditary angioneurotic edema . J Allergy. 1962;33:330-341.Crossref 13. Donaldson VH, Evans RR. A biochemical abnormality in hereditary angioneurotic edema: absence of serum inhibitor of C1-esterase . Am J Med. 1963;35:37-44.Crossref 14. Agostoni A, Cicardi M, Porreca W. Peripheral edema due to increased vascular permeability: a clinical appraisal . Int J Clin Lab Res. 1992;21:241-246.Crossref 15. Megerian CA, Arnold JE, Berger M. Angioedema: 5 years' experience, with a review of the disorder's presentation and treatment . Laryngoscope. 1992;102:256-260.Crossref 16. Erdos EG, Sloane E. An enzyme in human blood plasma that inactivates bradykinin and kallidins . Biochem Pharmacol. 1962;11:585-592.Crossref 17. Schweisfurth H, Reinhart E, Heinrich J, Brugger E. A simple spectrophotometric assay of carboxypeptidase N (kininase I) in human serum . J Clin Chem Clin Biochem. 1983;21:605-609. 18. Fleiss JL. The Mantel-Haenszel estimator in case-control studies with varying numbers of controls matched to each case . Am J Epidemiol. 1984;120:1-3.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440043007

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables. Abstract On the cover of the April issue of the Archives and in the article entitled "About the Cover" (1997;133:422-423), the photo credit was inadvertently omitted. Both photographs were taken by Phil Gunby of JAMA.

Stanganelli, Ignazio;Bauer, Paolo;Bucchi, Lauro;Serafini, Monica;Cristofolini, Paolo;Rafanelli, Silvia;Cristofolini, Mario

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440049008

Abstract Background: Current knowledge of the histologic counterparts of epiluminescence microscopy (ELM) features in pigmented skin lesions is limited. As a particular aspect of this problem, the transient effects of intense sun exposure on the morphological characteristics of melanocytic nevi may influence the expression of ELM features as well as the demonstration of stable and consistent histologic correlates. Observations: Forty melanocytic nevi from 11 subjects living in Northern Italy were examined by digital ELM before and after 5 to 13 days of sun exposure at latitudes of 5° north to 3° south. A number of multifaceted changes were observed. In particular, 3 lesions showed the expression of some structures compatible with radial streaming, pseudopods, and gray-blue areas. These features are considered to have often severe histologic correlates. In a third image, obtained 5 to 6 weeks later, they showed partial or total regression. Another case showed a massive regression of the pigment network as a result of a progressive inflammatory reaction with marked asymmetry in the distribution of pigmentation. Conclusions: Digital ELM has the potential to detect subtle changes in the structure of nevi after intense sun exposure. The transient observation of certain ELM features often associated with severe histologic substrates casts doubts on the ability of ELM to characterize sunexposed nevi by a single examination.Arch Dermatol. 1997;133:979-982 References 1. Pehamberger H, Steiner A, Wolff K. In vivo epiluminescence microscopy, I: pattern analysis of pigmented skin lesions . J Am Acad Dermatol. 1993;17:571-583.Crossref 2. Pehamberger H, Binder M, Steiner A, Wolff K. In vivo epiluminescence microscopy: improvement of early diagnosis of melanoma . J Invest Dermatol. 1983; 100:356S-362S.Crossref 3. Steiner A, Pehamberger H, Wolff K. In vivo epiluminescence microscopy, II: diagnosis of small pigmented skin lesions and early detection of malignant melanoma . J Am Acad Dermatol. 1987;17:584-591.Crossref 4. Steiner A, Binder M, Schemper M, Wolff K, Pehamberger H. Statistical evaluation of epiluminescence microscopy criteria for melanocytic pigmented skin lesions . J Am Acad Dermatol. 1993;29:581-588.Crossref 5. Soyer HP, Smolle J, Hodl S, Pachernegg H, Kerl H. Surface microscopy: a new approach to the diagnosis of cutaneous pigmented tumors . Am J Dermatopathol. 1989;11:1-10.Crossref 6. Soyer HP, Kerl H. Microscopie de surface des tumeurs cutanées pigmentées . Ann Dermatol Venereol. 1993;120:15-20. 7. Kenet RO, Kang S, Kenet BJ, Fitzpatrick TB, Sober AJ, Barnhill RL. Clinical diagnosis of pigmented lesions using digital epiluminescence microscopy . Arch Dermatol. 1993;129:157-174.Crossref 8. Bahmer FA, Fritsch P, Kreusch J, et al. Terminology in surface microscopy . JAm Acad Dermatol. 1990;23:1159-1162.Crossref 9. Yadav S, Vossaert KA, Kopf AW, Silverman M, Grin-Jorgensen C. Histologic correlates of structures seen on dermoscopy (epiluminescence microscopy) . Am J Dermatopathol. 1993;15:297-305.Crossref 10. Sober AJ. Digital epiluminescence microscopy in the evaluation of pigmented lesions: a brief review . Semin Surg Oncol. 1993;9:198-201. 11. Stanganelli I, Burroni M, Rafanelli S, Bucchi L. Intraobserver agreement in interpretation of digital epiluminescence microscopy . J Am Acad Dermatol. 1995; 33:584-589.Crossref 12. Epstein A. Instrumentation for epiluminescence microscopy: the gap between research and practice . Arch Dermatol. 1996;132:91-92.Crossref 13. Stanganelli I, Rafanelli S, Bucchi L. Seasonal prevalence of digital epiluminescence microscopy patterns in acquired melanocytic nevi . J Am Acad Dermatol. 1996;34:460-464.Crossref 14. Holman CDJ, Heenan PJ, Caruso V, Glancy RJ, Armstrong BK. Seasonal variation in the junctional component of pigmented naevi . Int J Cancer. 1983;31:213-215.Crossref 15. Tronnier M, Smolle J, Wolf HH. Ultraviolet irradiation induces acute changes in melanocytic nevi . J Invest Dermatol. 1995;104:475-478.Crossref 16. Caputo R, Ackerman AB, Sison-Torre EQ. Pediatric Dermatology and Dermopathology . Philadelphia, Pa: Lea & Febiger; 1990:37-47. 17. Stolz W, Braun-Falco O, Bilek P, Landthaler M, Cognetta AB. Color Atlas of Dermatoscopy . Cambridge, Mass: Blackwell Publishers; 1994. 18. Stierner U, Augustsson A, Rosdahl I, Suurkula M. Regional distribution of common and dysplastic naevi in relation to melanoma site and sun exposure . Melanoma Res. 1991;1:367-375.Crossref 19. Kopf AW, Linsay AC, Rogers GS, Friedman RJ, Rigel DS, Levenstein M. Relationship of nevocytic nevi to sun exposure in dysplastic nevus syndrome . J Am Acad Dermatol. 1985;12:656-662.Crossref 20. Gallagher RP, McLean DI, Yang CP, et al. Suntan, sunburn, and pigmentation factors and the frequency of acquired melanocytic nevi in children . Arch Dermatol. 1990;126:770-776.Crossref 21. Rivers JK, Kelly JW, MacLennan R. The Eastern Australian Mole Study: constitutional factors and latitude considerations . Melanoma Res. 1993;3:57-58.Crossref 22. Fleming MG, Swan LS, Heenan PJ. Seasonal variation in the proliferation fraction of Australian common nevi . Am J Dermatopathol. 1991;13:463-466.Crossref 23. Armstrong BK, Heenan PJ, Caruso V, Glancy RJ, Holman DJ. Seasonal variation in the junctional component of pigmented nevi . Int J Cancer. 1984;34:441-442.Crossref 24. Stierner U, Rosdahl I, Augustsson A, Kagedal B. UVB irradiation induces melanocyte increase in both exposed and shielded human skin . J Invest Dermatol. 1989;92:561-564.Crossref 25. Elder DE. Human melanocytic neoplasms and their etiologic relationship with sunlight . J Invest Dermatol. 1989;92( (suppl 5) ):297S-303S.Crossref

Weinberg, Jeffrey M.;Mysliwiec, Angela;Turiansky, George W.;Redfield, Robert;James, William D.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440053009

Abstract Background: Viral folliculitis is an infrequently reported entity. The patients described herein were seen over a 12-year period of practice in a referral dermatologic setting. The cases involve a variety of viral infections limited to the hair follicle. Observations: We describe 5 patients with a variety of viral folliculitides: 2 with herpetic sycosis caused by herpes simplex; 1 with herpex simplex folliculitis (this patient also had human immunodeficiency virus); 1 with herpes zoster without blisters; and 1 with molluscum contagiosum. Conclusions: These 5 cases demonstrate that viral folliculitis has varied causes and presentations. Clinicians should consider viral agents in the differential diagnosis of superficial infectious folliculitis, especially in cases that are refractory to antibacterial or antifungal therapy.Arch Dermatol. 1997;133:983-986 References 1. Izumi AK, Kim R, Arnold H Jr. Herpetic sycosis: report of two cases . Arch Dermatol. 1972;106:372-374.Crossref 2. Miliauskas JR, Leong AS-Y. Localized herpes simplex lymphadenitis: report of three cases and review of the literature . Histopathology . 1991;19:355-360.Crossref 3. Sexton M. Occult herpesvirus folliculitis clinically simulating pseudolymphoma . Am J Dermatopathol. 1991;13:234-240.Crossref 4. Muhlemann MF, Anderson MG, Paradinas FJ, et al. Early warning skin signs in AIDS and persistent generalized lymphadenopathy . Br J Dermatol. 1986;114: 419-424.Crossref 5. Barlow RJ, Schulz EJ. Necrotizing folliculitis in AIDS-related complex . Br J Dermatol. 1987;116:581-584.Crossref 6. Jacobson MA, Berger TG, Fikrig S, et al. Acyclovir-resistant varicella-zoster infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS) . Ann Intern Med. 1990;112:187-191.Crossref 7. Crowe SM. Unusual features of herpes simplex or zoster infection that suggest HIV infection . Med J Aust. 1993;158:186-187. 8. Cockerell CJ. Human immunodeficiency virus and the skin . Arch Intern Med. 1991; 151:1295-1303.Crossref 9. Lewis GW. Zoster sine herpete . BMJ. 1958;2:418-421.Crossref 10. Krishnamurthy J. Viral sycosis . Arch Dermatol. 1974;109:578.Crossref 11. Schwartz JJ, Myskowski PL. Molluscum contagiosum in patients with human immunodeficiency virus infection: a review of twenty-seven patients . J Am Acad Dermatol. 1992;27:583-588.Crossref 12. McSorley J, Shapiro L, Brownstein MH, Hsu KC. Herpes simplex and varicellazoster: comparative histopathology of 77 cases . Int J Dermatol. 1974;13:69-75.Crossref

Meadows, Kappa P.;Tyring, Stephen K.;Pavia, Andrew T.;Rallis, Tena M.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440061010

Abstract Background: Molluscum contagiosum virus (MCV) causes cutaneous skin growths that mainly affect children, sexually active adults, and immunocompromised individuals. Lesions of MCV in patients infected with human immunodeficiency virus can be large and numerous, and response to available treatments is often unsatisfactory. Observations: We describe 3 men infected with human immunodeficiency virus who presented with extensive MCV lesions that were not responsive to various treatments. Patient 1 demonstrated dramatic clearing of his MCV lesions when intravenous cidofovir therapy was started for his treatment-resistant bilateral CMV retinitis and because of cidofovir's possible activity against MCV. In case 2, cidofovir was compounded as a 3% cream in a combination vehicle (Dermovan) for extensive facial involvement, and complete resolution of MCV was seen after 1 month of therapy. In case 3, intravenous cidofovir therapy was started both for CMV retinitis and in an attempt to clear 90% facial MCV involvement; after 1 month of treatment, all clinical evidence of MCV had resolved.All 3 patients remain clear of recurrence. Conclusions: Cidofovir, a nucleotide analog of deoxycytidine monophosphate, appears to have contributed to clearing of advanced MCV lesions in these 3 patients, thus providing suggestive evidence of clinical activity against MCV. Controlled trials of cidofovir therapy for MCV in persons infected with human immunodeficiency virus are warranted.Arch Dermatol. 1997;133:987-990 References 1. Gottlieb SL, Myskowski PL. Molluscum contagiosum . Int J Dermatol. 1994;33: 453-461.Crossref 2. Schwartz JJ, Myskowski PL. Molluscum contagiosum in patients with human immunodeficiency virus infection: a review of twenty-seven patients . J Am Acad Dermatol. 1992;27:583-588.Crossref 3. Buller RM, Burnett J, Chen W, Kreider J. Replication of molluscum contagiosum virus . Virology. 1995;213:655-659.Crossref 4. Sonntag KC, Clauer U, Bugert JJ, Schnitzler P, Darai G. Identification and properties of the genes encoding the poly(A) polymerase and a small (22 kDa) and the largest subunit (147 kDa) of the DNA-dependent RNA polymerase of molluscum contagiosum virus . Virology. 1995;210:471-478.Crossref 5. Senkevich TG, Bugert JJ, Sisler JR, Koonin EV, Darai G, Moss B. Genome sequence of a human tumorigenic poxvirus: prediction of specific host responseevasion genes . Science . 1996;273:813-816.Crossref 6. Cherrington JM, Miner R, Hitchcock MJ, Lalezari JP, Drew WL. Susceptibility of human cytomegalovirus to cidofovir is unchanged after limited in vivo exposure to various regimens of drug . J Infect Dis. 1996;173:987-992.Crossref 7. Cronin TA, Resnik BI, Elgart G, Kerdel FA. Recalcitrant giant molluscum contagiosum in a patient with AIDS . J Am Acad Dermatol. 1996;35:266-267.Crossref 8. Bartlett JG. Protease inhibitors for HIV infection . Ann Intern Med. 1996;124: 1086-1088.Crossref 9. Benhamou Y, Katlama C, Lunel F, et al. Effects of lamivudine on replication of hepatitis B virus in HIV-infected men . Ann Intern Med. 1996;125:705-712.Crossref 10. Havlir D, Cheeseman SH, McLaughlin M, et al. High-dose nevirapine: safety, pharmokinetics, and antiviral effect in patients with HIV infection . J Infect Dis. 1995; 171:537-545.Crossref 11. De Castro LM, Kern ER, De Clercq E, et al. Phosphonylmethoxyalkyl purine and pyrimidine derivatives for treatment of opportunistic cytomegalovirus and herpes simplex virus infections in murine AIDS . Antiviral Res. 1991;16:101-114.Crossref 12. Gordon YJ, Romanowski EG, Araullo Cruz T. Topical HPMPC inhibits adenovirus type 5 in the New Zealand rabbit ocular replication model . Invest Ophthalmol Vis Sci. 1994;35:4135-4143. 13. Lalezari JP, Stagg RJ, Jaffe HS, Hitchcock MJM, Drew WL. A preclinical and clinical overview of the nucleotide-based antiviral agent cidofovir (HPMPC) . In: Mills J, ed. Antiviral Chemotherapy 4 . New York, NY: Plenum Publishing Corp; 1996: 105-115. 14. Van Cutsem E, Snoeck R, Van Ranst M, et al. Successful treatment of a squamous papilloma of the hypopharynx-esophagus by local injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine . J Med Virol. 1995;45:230-235.Crossref 15. Neyts J, De Clercq E. Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine for the treatment of lethal vaccinia virus infections in severe combined immune deficiency (SCID) mice . J Med Virol. 1993;41:242-246.Crossref 16. Earl P, Jones E, Moss B. Homology between DNA polymerases of poxviruses, herpesviruses, and adenoviruses . Proc Natl Acad Sci U S A. 1986;83:3659-3663.Crossref 17. Kriesel J, Douglas J, Corey L, et al. A phase I/II study of cidofovir topical gel for refractory condyloma acuminatum in patients with HIV infection . Presented at the Fourth Conference on Retroviruses and Opportunistic Infections; January 23, 1997; Washington, DC .

Knoell, Keith A.;Hendrix, John D.;Patterson, James W.;McHargue, Chauncey A;Wilson, Barbara B.;Greer, Kenneth E.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440066011

Abstract Background: Dysplastic melanocytic nevi (DMN) are thought to represent a clinical and histologic bridge between common pigmented nevi and superficial spreading malignant melanoma. The following clinical criteria for DMN were established to aid in the proper identification of these lesions: irregular perimeter, size exceeding 5 mm in diameter, background erythema, and variegated color (shades of browns, tans, blacks, and reds). Histologic features include basilar melanocytic proliferation with nuclear atypia, a patchy lymphocytic infiltrate with concentric eosinophilic fibroplasia, and lamellar fibroplasia. To our knowledge, there have been no previously reported cases of uniformly nonpigmented DMN. Observations: A 31-year-old brown-haired, brown-eyed white woman with no personal or family history of either DMN or melanoma presented for evaluation of numerous, discrete, nonindurated, 2- to 5-mm-diameter, nonpigmented macules and slightly elevated papules that had appeared in a truncal distribution over the course of several years. Microscopic examination of these lesions showed lentiginous epidermal hyperplasia and disordered proliferation with variable cellular atypia of intraepidermal melanocytes. Conclusions: Nonpigmented, nonindurated, macular or slightly elevated papular lesions may represent nevi with features of dysplasia. In light of the significant risk of malignant melanoma that is associated with pigmented varieties of dysplastic nevi, it is essential that clinicians consider nonpigmented DMN in the differential diagnosis of entities that present as hypopigmented macules.Arch Dermatol. 1997;133:992-994 References 1. Clark WH, Reimer RR, Greene MH, Ainsworth AM, Mastrangelo MJ. Origin of familial melanomas from heritable melanocytic lesions . Arch Dermatol. 1978; 114:732-738.Crossref 2. Greene MH, Clark WH, Tucker MA, et al. Acquired precursors of cutaneous melanoma: the familial dysplastic nevus syndrome . N Engl J Med. 1985;312:91-97.Crossref 3. Rhodes AR, Harrist TJ, Day CL, Mihm MC Jr, Fitzpatrick TB, Sober AJ. Dysplastic nevi in histologic association with 234 primary cutaneous melanomas . J Am Acad Dermatol. 1983;9:563-574.Crossref 4. Duray PH, Ernstoff MS. Dysplastic nevus in histologic contiguity with acquired nonfamilial melanoma . Arch Dermatol. 1987;123:80-84.Crossref 5. Clark WH, Elder DE, Guerry D IV, Epstein MN, Greene MH, Van Horn M. A study of tumor progression: the precursor lesion of superficial spreading and nodular melanoma . Hum Pathol. 1984;15:1147-1165.Crossref 6. Halpern AC, DuPont G, Elder DE, et al. Dysplastic nevi as risk markers of sporadic (nonfamilial) melanoma . Arch Dermatol. 1991;127:995-999.Crossref 7. NIH Consensus Development Panel on Early Melanoma. Diagnosis and treatment of early melanoma . JAMA. 1992;268:1314-1319.Crossref 8. Albert LS, Rhodes AR, Sober AS. Dysplastic melanocytic nevi and cutaneous melanoma: markers for increased melanoma risk for affected persons and blood relatives . J Am Acad Dermatol. 1990;22:69-75.Crossref 9. Kang S, Barnhill RL, Mihm MC, Fitzpatrick TB, Sober AJ. Melanoma risk in individuals with clinically atypical nevi . Arch Dermatol. 1994;130:999-1001..Crossref 10. Tucker MA, Fraser MC, Goldstein AM, Elder DE, Guerry D IV, Organic SM. Risk of melanoma and other cancers in melanoma-prone families . J Invest Dermatol. 1993;100:350S-355S.Crossref 11. Rigel DS, Rivers JK, Kopf AW, et al. Dysplastic nevi: markers for increased risk for melanoma . Cancer . 1989;63:386-389.Crossref 12. Theirston A, Grin C, Kopf A. Prospective follow-up for malignant melanoma in patients with atypical mole (dysplastic nevus) syndrome . J Dermatol Surg Oncol. 1991;17:44-48. 13. Elder DE, Greene MH, Guerry DIV, Kraemer KH, Clark WH. The dysplastic nevus syndrome: our definition . Am J Dermatopathol. 1982;4:455-460.Crossref 14. Kelly J, Crutcher W, Sagebiel R. Clinical diagnosis of dysplastic nevi . J Am Acad Dermatol. 1986;14:1044-1052.Crossref 15. Barnhill RL, Roush GC, Duray PH. Correlation of histologic architectural and cytoplasmic features with nuclear atypia in atypical (dysplastic) nevomelanocytic nevi . Hum Pathol. 1990;21:51-58.Crossref 16. Rhodes AR, Mihm MC Jr, Weinstock MA. Dysplastic melanocytic nevi: a reproducible histologic definition emphasizing cellular morphology . Mod Pathol. 1989; 2:306-319. 17. Grosshans E, Sengel D, Heid E. La lentiginose blanche . Ann Dermatol Venereol. 1994;121:7-10. 18. Cummings KI, Collel WI. Idiopathic guttate hypomelanosis . Arch Dermatol. 1966; 93:184-186.Crossref 19. Whitehead WJ, Moyer DG, Vander DE. Idiopathic guttate hypomelanosis . Arch Dermatol. 1966;94:279-281.Crossref 20. Ploysangam T, Dee-Ananlap S, Suvanprakorn P. Treatment of idiopathic guttate hypomelanosis with liquid nitrogen: light and electron microscopic studies . J Am Acad Dermatol. 1990;23:681-684.Crossref 21. Falabella R, Escobar CE, Carrascal E, Arroyave JA. Leukoderma punctata . J Am Acad Dermatol. 1988;18:485-494.Crossref 22. Kraemer K, Greene MH, Tarone R, Elder DE, Clark WH Jr, Guerry D IV. Dysplastic naevi and cutaneous melanoma risk . Lancet . 1983;2:1076-1077.Crossref 23. Elder DE, Goldman LI, Goldman SC, Greene MH, Clark WH Jr. Dysplastic nevus syndrome: a phenotypic association of sporadic cutaneous melanoma . Caner . 1980;46:1787-1794.Crossref 24. Newton JA, Bataille V, Griffiths K, et al. How common is the atypical mole phenotype in apparently sporadic melanoma? J Am Acad Dermatol. 1993;29:989-995.Crossref 25. Kraemer KH. Dysplastic nevi as precursors to hereditary melanoma . J Dermatol Surg Oncol. 1983;9:619-622.Crossref 26. Kraemer KH, Tucker M, Tarone R, Elder DE, Clark WH Jr. Risks of cutaneous melanoma in dysplastic nevus syndrome types A and B . N Engl J Med. 1986; 315:1615-1616.Crossref 27. Tucker MA, Halpern A, Holly EA, et al. Clinically recognized dysplastic nevi: a central risk factor for cutaneous melanoma . JAMA. 1997;277:1439-1444.Crossref 28. Green MH, Clark WH Jr, Tucker MA, Kraemer KH, Elder DE, Fraser MC. High risk of malignant melanoma in melanoma-prone families with dysplastic nevi . Ann Intern Med. 1985;120:458-465.Crossref 29. Nordlund JJ, Kirkwood J, Forget BM, et al. Demographic study of clinically atypical (dysplastic) nevi in patients with melanoma and comparison subjects . Cancer Res. 1985;45:1855-1861.

Piepkorn, Michael;Weinstock, Martin A.;Barnhill, Raymond L.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440073012

Abstract Nearly a century of clinical inquiry has failed to incontrovertibly resolve the question of whether elective lymph node dissection is therapeutically beneficial in the management of clinically localized melanoma. The controversy has been renewed by a recent interim update from the Intergroup Melanoma Surgical Program, sponsored by the National Cancer Institute, which has indicated a small survival benefit in a narrowly defined subgroup of patients with primary melanoma. That report stimulated this review of the data, which are presented in the historical context that originally prompted the Intergroup study. Case selection bias has intractably hindered firm conclusions from the numerous nonrandomized studies of elective lymphadenectomy. The two original randomized trials that were executed during the 1970s failed to uncover any significant effect of the procedure on survival. Definitive conclusions from the recent Intergroup report are limited by the likelihood that the observed therapeutic benefits are a chance occurrence resulting from uncorrected multiple subgroup comparisons. It remains uncertain whether elective lymphadenectomy can be therapeutically beneficial in the management of melanoma. Nevertheless, it is clear that the procedure, or preferably sentinel lymphatic mapping with selective lymphadenectomy, can provide clinically relevant prognostic information, as well as the staging data requisite to adjuvant interferon alfa-2b therapy or enrollment into other adjunctive trials for patients at high risk of clinical relapse. Arch Dermatol. 1997;133:995-1002 References 1. References 32, 36, 42, 45, 50, 53, 56, 58-71 2. References 4, 28, 29, 33-35, 37, 39, 46, 47, 53, 69, 77-79 3. Balch CM. The role of elective lymph node dissection in melanoma: rationale, results, and controversies . J Clin Oncol. 1988;6:163-172. 4. Halsted WS. The results of radical operations for the cure of carcinoma of the breast . Ann Surg. 1907;46:1-19.Crossref 5. Conrad FG. Treatment of malignant melanoma: wide excision alone vs lymphadenectomy . Arch Surg. 1972;104:587-592.Crossref 6. Morton DL, Wen D-R, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma . Arch Surg. 1992;127:392-399.Crossref 7. Balch CM, Soong S-J, Bartolucci AA, et al. Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger . Ann Surg. 1996; 224:255-266.Crossref 8. Smith B, Selby P, Southgate J, Pittman K, Bradley C, Blair GE. Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction . Lancet. 1991; 338:1227-1229.Crossref 9. Scott RN, McKay AJ. Elective lymph node dissection in the management of malignant melanoma . Br J Surg. 1993;80:284-288.Crossref 10. Lyons JH III, Cockerell CJ. Elective lymph node dissection for melanoma . J Am Acad Dermatol. 1994;30:467-480.Crossref 11. Harris MN, Shapiro RL, Roses DF. Malignant melanoma: primary surgical management (excision and node dissection) based on pathology and staging . Cancer. 1995;75( (suppl) ):715-725.Crossref 12. Johnson TM, Smith JWII, Nelson BR, Chang A. Current therapy for cutaneous melanoma . J Am Acad Dermatol. 1995;32:689-707.Crossref 13. Stone CA, Goodacre TEE. Surgical management of regional lymph nodes in primary cutaneous malignant melanoma . Br J Surg. 1995; 82:1015-1022.Crossref 14. Eve F. A lecture on melanoma . Practitioner. 1903; 70:165-174. 15. Pringle JH. A method of operation in cases of melanotic tumors of the skin . Edinb Med J. 1908; 23:496-499. 16. Broders AC, MacCarty WC. Melanoepithelioma: a report of seventy cases . Surg Gynecol Obstet. 1916;23:28-32. 17. Handley WS. Prognosis of simple moles and melanotic sarcoma . Lancet. 1935;1:1401-1402.Crossref 18. Handley WS. The pathology of melanotic growths in relation to their operative treatment . Lancet. 1907;1:927-935. 19. Bickel WH, Meyerding HW, Broders AC. Melanoepithelioma (melanosarcoma, melanocarcinoma, malignant melanoma) of the extremities . Surg Gynecol Obstet. 1943;76:570-576. 20. Sylvén B. Malignant melanoma of the skin: report of 341 cases treated during the years 1929-1943 . Acta Radiol. 1949;32:33-59.Crossref 21. Lund RH, Ihnen M. Malignant melanoma: clinical and pathologic analysis of 93 cases—is prophylactic lymph node dissection indicated? Surgery. 1955;38:652-659. 22. O'Rourke MGE, Louie A. Metastases in malignant melanoma . Aust N Z J Surg. 1982;52:154-158.Crossref 23. Cascinelli N, Preda F, Vaglini M, et al. Metastatic spread of stage I melanoma of the skin . Tumori. 1983;69:449-454. 24. McCarthy WH, Shaw HM, Thompson JF, Milton GW. Time and frequency of recurrence of cutaneous stage I malignant melanoma with guidelines for follow-up study . Surg Gynecol Obstet. 1988;166:497-502. 25. Fusi S, Ariyan S, Sternlicht A. Data on first recurrence after treatment for malignant melanoma in a large patient population . Plast Reconstr Surg. 1993;91:94-98.Crossref 26. Slingluff CL, Stidham KR, Ricci WM, Stanley WE, Seigler HF. Surgical management of regional lymph nodes in patients with melanoma: experience with 4682 patients . Ann Surg. 1994;219:120-130.Crossref 27. Meyskens FL Jr, Berdeaux DH, Parks B, Tong T, Loescher L, Moon TE. Cutaneous malignant melanoma (Arizona Cancer Center experience), I: natural history and prognostic factors influencing survival in patients with stage I disease . Cancer. 1988;62:1207-1214.Crossref 28. Fisher SR. Cutaneous malignant melanoma of the head and neck . Laryngoscope. 1989;99:822-836.Crossref 29. Milton GW, Shaw HM, Farago GM, McCarthy WH. Tumour thickness and the site and time of first recurrence in cutaneous malignant melanoma (stage I) . Br J Surg. 1980;67:543-546.Crossref 30. Day CL, Sober AJ, Lew RA, et al. Malignant melanoma patients with positive nodes and relatively good prognoses: microstaging retains prognostic significance in clinical stage I melanoma patients with metastases to regional nodes . Cancer. 1981;47:955-962.Crossref 31. Callery C, Cochran AJ, Roe DJ, et al. Factors prognostic for survival in patients with malignant melanoma spread to the regional lymph nodes . Ann Surg. 1982;196:69-75.Crossref 32. Pack GT, Scharnagel I, Morfit M. The principle of excision and dissection in continuity for primary and metastatic melanoma of the skin . Surgery. 1945;17:849-866. 33. Preston FW, Powers RC, Clarke TH, Walsh WS. Malignant melanoma: treatment and endresults in two hundred and twenty-five cases . Arch Surg. 1954;69:385-392.Crossref 34. Fortner JG, Booher RJ, Pack GT. Results of groin dissection for malignant melanoma in 220 patients . Surgery. 1964;55:485-494. 35. McNeer G, Das Gupta T. Prognosis in malignant melanoma . Surgery. 1964;56:512-518. 36. Gumport SL, Harris MN. Results of regional lymph node dissection for melanoma . Ann Surg. 1974;179:105-108.Crossref 37. Cohen MH, Ketcham AS, Felix EL, et al. Prognostic factors in patients undergoing lymphadenectomy for malignant melanoma . Ann Surg. 1977;186:635-642.Crossref 38. Fortner JG, Woodruff J, Schottenfeld D, MacLean B. Biostatistical basis of elective lymph node dissection for malignant melanoma . Ann Surg. 1977; 186:101-103.Crossref 39. Davis NC. Cutaneous melanoma: the Queensland experience . Curr Probl Surg. 1976;13:1-63.Crossref 40. Kapelanski DP, Block GE, Kaufman M. Characteristics of the primary lesion of malignant melanoma as a guide to prognosis and therapy . Ann Surg. 1979;189:225-235.Crossref 41. Ariel IM. Malignant melanoma of the trunk: a retrospective review of 1128 patients . Cancer. 1982; 49:1070-1078.Crossref 42. McCarthy WH, Shaw HM, Milton GW. Efficacy of elective lymph node dissection in 2,347 patients with clinical stage I malignant melanoma . Surg Gynecol Obstet. 1985;161:575-580. 43. Elder DE, Guerry D IV, VanHorn M, et al. The role of lymph node dissection for clinical stage I malignant melanoma of intermediate thickness (1.51-3.99 mm) . Cancer. 1985;56: 413-418.Crossref 44. Karakousis CP, Emrich LJ, Rao U. Groin dissection in malignant melanoma . Am J Surg. 1986; 152:491-495.Crossref 45. Bowsher WG, Taylor BA, Hughes LE. Morbidity, mortality and local recurrence following regional node dissection for melanoma . Br J Surg. 1986;73:906-908.Crossref 46. Silberman AW. Malignant melanoma: practical considerations concerning prophylactic regional lymph node dissection . Ann Surg. 1987;206:206-209.Crossref 47. Cochran AJ, Wen D-R, Morton DL. Occult tumor cells in the lymph nodes of patients with pathological stage I malignant melanoma . Am J Surg Pathol. 1988;12:612-618.Crossref 48. Coit DG, Brennan MF. Extent of lymph node dissection in melanoma of the trunk or lower extremity . Arch Surg. 1989;124:162-166.Crossref 49. Karakousis CP, Hena MA, Emrich LJ, Driscoll DL. Axillary node dissection in malignant melanoma: results and complications . Surgery. 1990; 108:10-17. 50. Hansson J, Ringborg U, Lagerlöf B, et al. Elective lymph node dissection in stage I cutaneous malignant melanoma of the head and neck: a report from the Swedish Melanoma Study Group . Melanoma Res. 1994;4:407-411.Crossref 51. Coates AS, Ingvar CI, Petersen-Schaefer K, et al. Elective lymph node dissection in patients with primary melanoma of the trunk and limbs treated at the Sydney Melanoma Unit from 1960 to 1991 . J Am Coll Surg. 1995;180:402-409. 52. Wanebo HJ, Woodruff J, Fortner JG. Malignant melanoma of the extremities: a clinicopathologic study using levels of invasion (microstage) . Cancer. 1975;35:666-676.Crossref 53. Holmes EC, Clark W, Morton DL, Eilber FR, Bochow AJ. Regional lymph node metastases and the level of invasion of primary melanoma . Cancer. 1976;37:199-201.Crossref 54. Holmes EC, Moseley HS, Morton DL, Clark W, Robinson D, Urist MM. A rational approach to the surgical management of melanoma . Ann Surg. 1977;186:481-490.Crossref 55. Das Gupta TK. Results of treatment of 269 patients with primary cutaneous melanoma: a five-year prospective study . Ann Surg. 1977;186: 201-209.Crossref 56. Balch CM, Murad TM, Soong S-J, Ingalls AL, Richards PC, Maddox WA. Tumor thickness as a guide to surgical management of clinical stage I melanoma patients . Cancer. 1979;43:883-888.Crossref 57. Veronesi U, Adamus J, Bandier DC, et al. Stage I melanoma of the limbs: immediate versus delayed node dissection . Tumori. 1980;66:373-396. 58. Martijn H, Oldhoff J, Oosterhuis JW, Koops HS. Indications for elective groin dissection in clinical stage I patients with malignant melanoma of the lower extremity treated by hyperthermic regional perfusion . Cancer. 1983;52:1526-1534.Crossref 59. Carmichael VE, Robins RE, Wilson KS. Elective and therapeutic regional lymph node dissection for cutaneous malignant melanoma: experience of the British Columbia Cancer Agency, 1972 to 1981 . Can J Surg. 1992;35:600-604. 60. Pack GT, Gerber DM, Scharnagel IM. End results in the treatment of malignant melanoma: a study of 1190 cases . Ann Surg. 1952;136:905-911.Crossref 61. Lane N, Lattes R, Malm J. Clinicopathological correlations in a series of 117 malignant melanomas of the skin of adults . Cancer. 1958;11:1025-1043.Crossref 62. Gumport SL, Meyer HW. Treatment of 126 cases of malignant melanoma: long term results . Ann Surg. 1959;150:989-992.Crossref 63. Charalambidis PH, Patterson WB. A clinical study of 250 patients with malignant melanoma . Surg Gynecol Obstet. 1962;115:333-341. 64. Guiss LW, MacDonald I. The role of radical regional lymphadenectomy in treatment of melanoma . Am J Surg. 1962;104:135-141.Crossref 65. Mundth ED, Guralnick EA, Raker JW. Malignant melanoma: a clinical study of 427 cases . Ann Surg. 1965;162:15-28.Crossref 66. Lehman JA Jr, Cross FS, Richey dWG. Clinical study of forty-nine patients with malignant melanoma . Cancer. 1966;19:611-619.Crossref 67. Lehr HB, Royster HP, Enterline HT, Askovitz SI. The surgical management of patients with melanoma . Plast Reconstr Surg. 1967;40:475-481.Crossref 68. Goldsmith HS, Shah JT, Kim D-H. Prognostic significance of lymph node dissection in the treatment of malignant melanoma . Cancer. 1970;26: 606-609.Crossref 69. Karakousis CP, Seddiq MK, Moore R. Prognostic value of lymph node dissection in malignant melanoma . Arch Surg. 1980;115:719-722.Crossref 70. Roses DF, Harris MN, Grunberger I, Gumport SL. Selective surgical management of cutaneous melanoma of the head and neck . Ann Surg. 1980; 192:629-632.Crossref 71. Balch CM, Soong S-J, Murad TM, Ingalls AL, Maddox WA. A multifactorial analysis of melanoma, III: prognostic factors in melanoma patients with lymph node metastases (stage II) . Ann Surg. 1981;193:377-388.Crossref 72. Day CL, Mihm MC, Lew RA, et al. Prognostic factors for patients with clinical stage I melanoma of intermediate thickness (1.51-3.99 mm) . Ann Surg. 1982;195:35-43.Crossref 73. Gadd MA, Coit DG. Recurrence patterns and outcome in 1019 patients undergoing axillary or inguinal lymphadenectomy for melanoma . Arch Surg. 1992;127:1412-1416.Crossref 74. Goldman LI, Clark WH Jr, Bernardino EA, Ainsworth AM. The accuracy of predicting lymph node metastases in malignant melanoma by clinical examination and microstaging . Ann Surg. 1976; 184:537-540.Crossref 75. Johnson RE. Occult lymphatic metastases in malignant melanoma of the skin . Ann Surg. 1957; 146:931-936.Crossref 76. Petersen NC, Bodenham DC, Lloyd OC. Malignant melanomas of the skin: a study of the origin, development, aetiology, spread, treatment and prognosis, part II. Br J Plast Surg. 1962;15: 97-116.Crossref 77. Stehlin JS. Malignant melanoma: an appraisal . Surgery. 1968;64:1149-1157. 78. Bodenham DC. Malignant melanoma: the problem of lymph-node metastases . Proc R Soc Med. 1969;62:1090-1092. 79. Milton GW, Shaw HM, McCarthy WH, Pearson L, Balch CM, Soong S-J. Prophylactic lymph node dissection in clinical stage I cutaneous malignant melanoma: results of surgical treatment in 1319 patients . Br J Surg. 1982;69:108-111.Crossref 80. Roses DF, Provet JA, Harris MN, Gumport SL, Dubin N. Prognosis of patients with pathologic stage II cutaneous malignant melanoma . Ann Surg. 1985;201:103-107. 81. Morton DL, Wanek L, Nizze JA, Elashof RM, Wong JH. Improved long-term survival after lymphadenectomy of melanoma metastatic to regional nodes . Ann Surg. 1991;214:491-501.Crossref 82. Crowley NJ, Seigler HF. The role of elective lymph node dissection in the management of patients with thick cutaneous melanoma . Cancer. 1990; 66:2522-2527.Crossref 83. Stehlin JS, Clark RL. Melanoma of the extremities: experiences with conventional treatment and perfusion in 339 cases . Am J Surg. 1965;110: 366-383.Crossref 84. Stehlin JS Jr, Smith JL Jr, Jin BS, Sherrin D. Melanoma of the extremities complicated by intransit metastases . Surg Gynecol Obstet. 1966; 122:3-14. 85. McCarthy JG, Haagensen CD, Herter FP. The role of groin dissection in the management of melanoma of the lower extremity . Ann Surg. 1974; 179:156-159.Crossref 86. Cascinelli N, Bufalino R, Marolda R, et al. Regional non-nodal metastases of cutaneous melanoma . Eur J Surg Oncol. 1986;12:175-180. 87. Shaw JHF, Rumball EM. Complications and local recurrence following lymphadenectomy . Br J Surg. 1990;77:760-764.Crossref 88. Baas PC, Koops HS, Hoekstra HJ, van Bruggen JJ, van der Weele LT, Oldhoff J. Groin dissection in the treatment of lower-extremity melanoma . Arch Surg. 1992;127:281-286.Crossref 89. Pack GT. The management of pigmented nevi and malignant melanomas . South Med J. 1947;40: 832-838.Crossref 90. Block GE, Hartwell SW Jr. Malignant melanoma—a study of 217 cases, part II: treatment effects . Ann Surg. 1961;154( (suppl) ):88-101.Crossref 91. Polk HC, Linn BS. Selective regional lymphadenectomy for melanoma: a mathematical aid to clinical judgement . Ann Surg. 1971;174:402-413.Crossref 92. Pressman JJ, Simon MB. Experimental evidence of direct communications between lymph nodes and veins . Surg Gynecol Obstet. 1961; 113:537-541. 93. Cady B. 'Prophylactic' lymph node dissection in melanoma: does it help? J Clin Oncol. 1988;6: 2-4. 94. Mehnert JH, Heard JL. Staging of malignant melanomas by depth of invasion: a proposed index to prognosis . Am J Surg. 1965;110:168-176.Crossref 95. Balch CM, Soong S-J, Murad TM, Ingalls AL, Maddox WA. A multifactorial analysis of melanoma, II: prognostic factors in patients with stage I (localized) melanoma . Surgery. 1979;86:343-351. 96. Balch CM. Surgical management of regional lymph nodes in cutaneous melanoma . J Am Acad Dermatol. 1980;3:511-524.Crossref 97. Balch CM, Soong S-J, Milton GW, et al. A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia . Ann Surg. 1982;196: 677-684.Crossref 98. Reintgen DS, Cox EB, McCarty KS Jr, Vollmer RT, Seigler HF. Efficacy of elective lymph node dissection in patients with intermediate thickness primary melanoma . Ann Surg. 1983;198: 379-384.Crossref 99. Blois MS, Sagebiel RW, Tuttle MS, Caldwell TM, Taylor HW. Judging prognosis in malignant melanoma of the skin: a problem of inference over small data sets . Ann Surg. 1983;198:200-206.Crossref 100. Rompel R, Garbe C, Büttner P, Teichelmann K, Petres J. Elective lymph node dissection in primary malignant melanoma: a matched-pair analysis . Melanoma Res. 1995;5:189-194.Crossref 101. Hein DW, Moy RL. Elective lymph node dissection in stage I malignant melanoma: a meta-analysis . Melanoma Res. 1992;2:273-277.Crossref 102. Breslow A. Prognosis in stage I cutaneous melanoma: tumor thickness as a guide to treatment . In: Ackerman AB, ed. Pathology of Malignant Melanoma . New York, NY: Masson Publishing; 1981:313-319. 103. Breslow A. Tumor thickness, level of invasion and node dissection in stage I cutaneous melanoma . Ann Surg. 1975;182:572-575. 104. Veronesi U, Adamus J, Bandiera DC, et al. Inefficacy of immediate node dissection in stage I melanoma of the limbs . N Engl J Med. 1977; 297:627-630.Crossref 105. Veronesi U, Adamus J, Bandiera DC, et al. Delayed regional lymph nodes dissection in stage I melanoma of the skin of the lower extremities . Cancer. 1982;49:2420-2430.Crossref 106. McCarthy WH, Shaw HM, Cascinelli N, Santinami M, Belli F. Elective lymph node dissection for melanoma: two perspectives . World J Surg. 1992;16:203-213.Crossref 107. Sim FH, Taylor WF, Ivins JC, Pritchard DJ, Soule EH. A prospective randomized study of the efficacy of routine elective lymphadenectomy in management of malignant melanoma: preliminary results . Cancer. 1978;41:948-956.Crossref 108. Sim FH, Taylor WF, Pritchard DJ, Soule E. Lymphadenectomy in the management of stage I malignant melanoma: a prospective randomized study . Mayo Clin Proc. 1986;61:697-705.Crossref 109. Roberts SS, Hengesh JW, McGrath RG, Valaitis J, McGrew EA, Cole WH. Prognostic significance of cancer cells in the circulating blood: a ten year evaluation . Am J Surg. 1967;113:757-762.Crossref 110. Mellado B, Colomer D, Castel T, et al. Detection of circulating neoplastic cells by reverse-transcriptase polymerase chain reaction in malignant melanoma: association with clinical stage and prognosis . J Clin Oncol. 1996;14:2091-2097. 111. Price WE, DuVal MK. Regional lymph node dissection and malignant melanoma: effect on survival . Arch Surg. 1963;87:747-750.Crossref 112. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684 . J Clin Oncol. 1996; 14:7-17.

Sabroe, Ruth A.;Greaves, Malcolm W.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440085013

Abstract Chronic idiopathic urticaria (CIU) can be extremely disabling and difficult to treat, with little response to antihistamine therapy. The pathogenic mechanisms of the disease are not well understood, but the primary effector cell is the mast cell. Release of mast cell mediators can cause inflammation and accumulation and activation of other cells, including eosinophils, neutrophils, and possibly basophils. Recent work has demonstrated that about one third of patients with CIU have circulating functional histamine-releasing autoantibodies that bind to the high-affinity IgE receptor (FcεRI) or, less commonly, to IgE; mast cell— specific histamine-releasing activity that has not yet been fully characterized; no identifiable circulating histamine-releasing activity. The mainstay of treatment of CIU consists of antihistamines, but immunotherapy using plasmapheresis, intravenous immunoglobulin, and cyclosporin may be valuable in severely affected patients with treatment-resistant disease. The response to immunomodulation and the recent finding of an association with HLA DR4 lend further support for an autoimmune basis to CIU in some patients. Arch Dermatol. 1997;133:1003-1008 References 1. Greaves MW. Chronic urticaria . N Engl J Med. 1995;332:1767-1772.Crossref 2. Juhlin L. Incidence of intolerance to food additives . Int J Dermatol. 1980;19: 548-551.Crossref 3. Hellgren L. The prevalence of urticaria in the total population . Acta Allerologica. 1972;27:236-240.Crossref 4. Juhlin L. Recurrent urticaria: clinical investigation of 330 patients . Br J Dermatol. 1981;104:369-381.Crossref 5. Sibbald RG, Cheema AS, Lozinski A, Tarlo S. Chronic urticaria: evaluation of the role of physical, immunologic, and other contributory factors . Int J Dermatol. 1991;30:381-386.Crossref 6. O'Donnell BF, Lawlor F, Simpson J, Morgan M, Greaves MW. Chronic urticaria: impact on quality of life . Br J Dermatol. 1997;136:197-201.Crossref 7. Champion RH, Roberts SOB, Carpenter RG, Roger JH. Urticaria and angiooedema: a review of 554 patients . Br J Dermatol. 1969;81:588-597.Crossref 8. Krause LB, Shuster S. H1-receptor—active histamine not sole cause of chronic idiopathic urticaria . Lancet. 1984;2:929-930.Crossref 9. Jorizzo JL, Smith EB. The physical urticarias: an update and review . Arch Dermatol. 1982;118:194-201.Crossref 10. Barlow RJ, Warburton F, Watson K, Black AK, Greaves MW. Diagnosis and incidence of delayed pressure urticaria in patients with chronic urticaria . J Am Acad Dermatol. 1993;29:954-958.Crossref 11. Mehregan DR, Hall MJ, Gibson LE. Urticarial vasculitis: a histopathologic and clinical review of 72 cases . J Am Acad Dermatol. 1992;26:441-448.Crossref 12. Monroe EW. Urticarial vasculitis: an updated review . JAm Acad Dermatol. 1981; 5:88-95.Crossref 13. Weedon D. Urticarias . In: Weedon D, ed. The Skin . New York, NY: Churchill Livingstone Inc; 1992;9:215-219. 14. Russell Jones R, Bhogal B, Dash A, Schifferli J. Urticaria and vasculitis: a continuum of histological and immunopathological changes . Br J Dermatol. 1983; 108:695-703.Crossref 15. Michaëlsson G, Juhlin L. Urticaria induced by preservatives and dye additives in food and drugs . Br J Dermatol. 1973;88:525-532.Crossref 16. Warin RP, Smith RJ. Challenge test battery in chronic urticaria . Br J Dermatol. 1976;94:401-406.Crossref 17. Inman WHW, Rawson NSB, Wilton LV, Pearce GL, Speirs CJ. Postmarketing surveillance of enalapril, I: results of prescription-event monitoring . BMJ. 1988; 297:826-829.Crossref 18. Cameron HA, Higgins TJC. Clinical experience with lisinopril: observations on safety and tolerability . J Hum Hypertens. 1989;3:177-186. 19. Slater EE, Merrill DD, Guess HA, et al. Clinical profile of angioedema associated with angiotensin converting-enzyme inhibition . JAMA. 1988;260:967-970.Crossref 20. Niimi N, Francis DM, Kermani F, et al. Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria . J Invest Dermatol. 1996;106:1001-1006.Crossref 21. Mekori YA, Giorno RC, Anderson P, Kohler PF. Lymphocyte subpopulations in the skin of patients with chronic urticaria . J Allergy Clin Immunol. 1983;72: 681-684.Crossref 22. Elias J, Boss E, Kaplan AP. Studies of the cellular infiltrate of chronic idiopathic urticaria: prominence of T-lymphocytes, monocytes, and mast cells . J Allergy Clin Immunol. 1986;78:914-918.Crossref 23. Natbony SF, Phillips ME, Elias JM, Godfrey HP, Kaplan AP. Histologic studies of chronic idiopathic urticaria . J Allergy Clin Immunol. 1983;71:177-183.Crossref 24. Smith CH, Kepley C, Schwartz LB, Lee TH. Mast cell number and phenotype in chronic idiopathic urticaria . J Allergy Clin Immunol. 1995;96:360-364.Crossref 25. Barlow RJ, Ross EL, MacDonald DM, Kobza-Black A, Greaves MW. Mast cells and T lymphocytes in chronic urticaria . Clin Exp Allergy. 1995;25:317-322.Crossref 26. Peters MS, Schroeter AL, Kephart GM, Gleich GJ. Localization of eosinophil granule major basic protein in chronic urticaria . J Invest Dermatol. 1983;81: 39-43.Crossref 27. Peters MS, Winkelmann RK. Neutrophilic urticaria . Br J Dermatol. 1985;113: 25-30.Crossref 28. Winkelmann RK, Reizner GT. Diffuse dermal neutrophilia in urticaria . Hum Pathol. 1988;19:389-393.Crossref 29. Winkelmann RK, Wilson-Jones E, Smith NP, English JSC, Greaves MW. Neutrophilic urticaria . Acta Derm Venereol (Stockh) . 1988;68:129-133. 30. Sodhi N, Peterson EA, Schroeter AL, et al. Inflammatory cells in chronic urticaria . J Allergy Clin Immunol. 1990;85:204. 31. Dolovich J, Hargreave FE, Chalmers R, Shier KJ, Gauldie J, Bienenstock J. Late cutaneous allergic responses in isolated IgE-dependent reactions . J Allergy Clin Immunol. 1973;52:38-46.Crossref 32. Solley GO, Gleich GJ, Jordon RE, Schroeter AL. The late phase of the immediate wheal and flare skin reaction: its dependence upon IgE antibodies . J Clin Invest. 1976;58:408-420.Crossref 33. Charlesworth EN, Hood AF, Soter NA, Kagey-Sobotka A, Norman PS, Lichtenstein LM. Cutaneous late-phase response to allergen: mediator release and inflammatory cell infiltration . J Clin Invest. 1989;83:1519-1526.Crossref 34. Frew AJ, Kay AB. UCHL1+ (CD45RO +) 'memory'T cells predominate in the CD4+ cellular infiltrate associated with allergen-induced late-phase skin reactions in atopic subjects . Clin Exp Immunol. 1991;84:270-274.Crossref 35. Leiferman KM, Fujisawa T, Gray BH, Gleich GJ. Extracellular deposition of eosinophil and neutrophil granule proteins in the IgE-mediated cutaneous late phase reaction . Lab Invest. 1990;62:579-589. 36. Tsicopoulos A, Hamid Q, Haczku A, et al. Kinetics of cell infiltration and cytokine messenger RNA expression after intradermal challenge with allergen and tuberculin in the same atopic individuals . J Allergy Clin Immunol. 1994;94:767-772.Crossref 37. Nicod LP. Cytokines, I: overview . Thorax. 1993;48:660-667.Crossref 38. Marks R, Greaves MW. Vascular reactions to histamine and compound 48/80 in human skin: suppression by a histamine H2-receptor blocking agent . Br J Clin Pharmacol. 1977;4:367-369.Crossref 39. Robertson I, Greaves MW. Responses of human skin blood vessels to synthetic histamine analogues . Br J Clin Pharmacol. 1978;5:319-322.Crossref 40. Foreman JC. Neuropeptides and the pathogenesis of allergy . Allergy. 1987;42: 1-11.Crossref 41. Davies MG, Greaves MW. Sensory responses of human skin to synthetic histamine analogues and histamine . Br J Clin Pharmacol. 1980;9:461-465. 42. Kubes P, Kanwar S. Histamine induces leukocyte rolling in post-capillary venules: a P-selectin—mediated event . J Immunol. 1994;152:3570-3576. 43. Greaves MW, Sondergaard J. Urticaria pigmentosa and factitious urticaria: direct evidence for release of histamine and other smooth muscle—contracting agents in dermographic skin . Arch Dermatol. 1970;101:418-425.Crossref 44. Kaplan AP, Horáková Z, Katz SI. Assessment of tissue fluid histamine levels in patients with urticaria . J Allergy Clin Immunol. 1978;61:350-354.Crossref 45. Okahara K, Murakami T, Yamamoto S, Yata N. Skin microdialysis: detection of in vivo histamine release in cutaneous allergic reactions . Skin Pharmacol. 1995; 8:113-118.Crossref 46. Bleehen SS, Thomas SE, Greaves MW, et al. Cimetidine and chlorpheniramine in the treatment of chronic idiopathic urticaria: a multi-centre randomised double-blind study . Br J Dermatol. 1987;117:81-88.Crossref 47. Irani AA, Schechter NM, Craig SS, DeBlois G, Schwartz LB. Two types of human mast cells that have distinct neutral protease compositions . Proc Natl Acad Sci U S A. 1986;83:4464-4468.Crossref 48. Schwartz LB. Mast cells and their role in urticaria . J Am Acad Dermatol. 1991; 25:190-204.Crossref 49. Eady RAJ, Cowen T, Marshall TF, Plummer V, Greaves MW. Mast cell population density, blood vessel density and histamine content in normal human skin . Br J Dermatol. 1979;100:623-633.Crossref 50. Wiesner-Menzel L, Schulz B, Vakilzadeh F, Czarnetzki BM. Electron microscopical evidence for a direct contact between nerve fibres and mast cells . Acta Derm Venereol (Stockh) . 1981;61:465-469. 51. Bienenstock J, Tomioka M, Matsuda H, et al. The role of mast cells in inflammatory processes: evidence for nerve/mast cell interactions . Int Arch Allergy Immunol. 1987;82:238-243.Crossref 52. Greaves MW, Shuster S. Responses of human skin blood vessels to bradykinin, histamine and 5-hydroxytryptamine . J Physiol. 1967;193:255-267. 53. Bradding P, Feather IH, Howarth PH, et al. Interleukin 4 is localized to and released by human mast cells . J Exp Med. 1992;176:1381-1386.Crossref 54. Möller A, Lippert U, Lessmann D, et al. Human mast cells produce IL-8 . J Immunol. 1993;151:3261-3266. 55. Walsh LJ, Trinchieri G, Waldorf HA, Whitaker D, Murphy GF. Human dermal mast cells contain and release tumor necrosis factor a which induces endothelial leukocyte adhesion molecule 1 . Proc Natl Acad Sci U S A. 1991;88:4220-4224.Crossref 56. Bradding P, Roberts JA, Britten KM, et al. Interleukin-4, -5, and -6 and tumor necrosis factor-α in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines . Am J Respir Cell Mol Biol. 1994;10:471-480.Crossref 57. Okayama Y, Petit-Frére C, Kassel O, et al. IgE-dependent expression of mRNA for IL-4 and IL-5 in human lung mast cells . J Immunol. 1995;155:1796-1808. 58. Bressler RB. Pathophysiology of chronic urticaria . Immunol Allergy Clin North Am. 1995;15:659-677. 59. Plaut M, Pierce JH, Watson CJ, Hanley-Hyde J, Nordan RP, Paul WE. Mast cell lines produce lymphokines in response to cross-linkage of FcεR1 or to calcium ionophores . Nature. 1989;339:64-67.Crossref 60. Selvan RS, Butterfield JH, Krangel MS. Expression of multiple chemokine genes by a human mast cell leukemia . J Biol Chem. 1994;269:13893-13898. 61. Soter NA, Lewis RA, Corey EJ, Austen KF. Local effects of synthetic leukotrienes (LTC4, LTD4, LTE4, and LTB4) in human skin . J Invest Dermatol. 1983; 80:115-119.Crossref 62. Masinovsky B, Urdal D, Gallatin WM. IL-4 acts synergistically with IL-1β to promote lymphocyte adhesion to microvascular endothelium by induction of vascular cell adhesion molecule-1 . J Immunol. 1990;145:2886-2895. 63. Kanwar S, Johnston B, Kubes P. Leukotriene C4/D4 induces P-selectin and sialyl Lewisx-dependent alterations in leukocyte kinetics in vivo . Circ Res. 1995; 77:879-887.Crossref 64. Baggiolini M, Dahinden CA. CC chemokines in allergic inflammation . Immunol Today. 1994;15:127-133.Crossref 65. Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils . J Clin Invest. 1989;84:1045-1049.Crossref 66. Swain SL, Weinberg AD, English M, Huston G. IL-4 directs the development of Th2-like helper effectors . J Immunol. 1990;145:3796-3806. 67. Coffman RL, Ohara J, Bond MW, Carty J, Zlotnik A, Paul WE. B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells . J Immunol. 1986;136:4538-4541. 68. Levi-Schaffer F, Segal V, Shalit M. Effects of interleukins on connective tissue type mast cells co-cultured with fibroblasts . Immunology. 1991;72:174-180. 69. Madden KB, Urban JF, Ziltener HJ, Schrader JW, Finkelman FD, Katona IM. Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis . J Immumol. 1991;147:1387-1391. 70. Tsuji K, Nakahata T, Takagi M, et al. Effects of interleukin-3 and interleukin-4 on the development of 'connective tissue-type' mast cells: interleukin-3 supports their survival and interleukin-4 triggers and supports their proliferation synergistically with interleukin-3 . Blood. 1990;75:421-427. 71. Benyon RC, Robinson C, Church MK. Differential release of histamine and eicosanoids from human skin mast cells activated by IgE-dependent and non-immunological stimuli . Br J Pharmacol. 1989;97:898-904.Crossref 72. Jorizzo JL, Coutts AA, Eady RAJ, Greaves MW. Vascular responses of human skin to injection of substance P and mechanism of action . Eur J Pharmacol. 1983;87:67-76.Crossref 73. Wallengren J, Håkanson R. Effects of substance P, neurokinin A and calcitonin gene-related peptide in human skin and their involvement in sensory nervemediated responses . Eur J Pharmacol. 1987;143:267-273.Crossref 74. Brain SD, Tippins JR, Morris HR, Maclntyre I, Williams TJ. Potent vasodilator activity of calcitonin gene-related peptide in human skin . J Invest Dermatol. 1986; 87:533-536.Crossref 75. Castells MC, Irani A-M, Schwartz LB. Evaluation of human peripheral blood leukocytes for mast cell tryptase . J Immunol. 1987;138:2184-2189. 76. Valent P, Schmidt G, Besemer J, et al. Interleukin-3 is a differentiation factor for human basophils . Blood. 1989;73:1763-1769. 77. Ishizaka T, Mitsui H, Yanagicla M, Miura T, Dvorak AM. Development of human mast cells from their progenitors . Curr Opin Immunol. 1993;5:937-943.Crossref 78. Schroeder JT, MacGlashan DW, Kagey-Sobotka A, White JM, Lichtenstein LM. Cytokine generation by human basophils . J Allergy Clin Immunol. 1994;94: 1189-1195.Crossref 79. Valent P. The phenotype of human eosinophils, basophils, and mast cells . J Allergy Clin Immunol. 1994;94:1177-1183.Crossref 80. Ochensberger B, Rihs S, Brumler T, Dahinden CA. IgE-independent interleukin-4 expression and induction of a late phase of leukotriene formation in human blood basophils . Blood. 1995;86:4039-4049. 81. Naclerio RM, Proud D, Togias AG, et al. Inflammatory mediators in late antigeninduced rhinitis . N Engl J Med. 1985;313:65-70.Crossref 82. Shalit M, Schwartz LB, von Allmen C, Atkins PC, Lavker RM, Zweiman B. Release of histamine and tryptase during continuous and interrupted cutaneous challenge with allergen in humans . J Allergy Clin Immunol. 1990;86:117-125.Crossref 83. Malaviya R, Morrison AR, Pentland AP. Histamine in human epidermal cells is induced by ultraviolet light injury . J Invest Dermatol. 1996;106:785-789.Crossref 84. Kepley CL, Craig SS, Schwartz LB. Identification and partial purification of a unique marker for human basophils . J Immunol. 1995;154:6548-6555. 85. Greaves MW, Plummer VM, McLaughlan P, Stanworth DR. Serum and cell bound IgE in chronic urticaria . Clin Allergy. 1974;4:265-271.Crossref 86. Kern F, Lichtenstein LM. Defective histamine release in chronic urticaria . J Clin Invest. 1976;57:1369-1377.Crossref 87. Grattan CEH, Walpole DA, Dootson GM, Edler S, Francis DM, Corbett MF. Basophils in chronic urticaria . Clin Exp Dermatol. 1995;20:275-278. 88. Sutton BJ, Gould HJ. The human IgE network . Nature. 1993;336:421-428.Crossref 89. Lowman MA, Rees PH, Benyon RC, Church MK. Human mast cell heterogeneity: histamine release from mast cells dispersed from skin, lung, adenoids, tonsils, and colon in response to IgE-dependent and nonimmunologic stimuli . J Allergy Clin Immunol. 1988;81:590-597.Crossref 90. Grattan CEH, Wallington TB, Warin RP, Kennedy CTC, Bradfield JW. A serological mediator in chronic idiopathic urticaria: a clinical, immunological and histological evaluation . Br J Dermatol. 1986;114:583-590.Crossref 91. Kermani F, Niimi N, Francis DM, et al. Characterization of a novel mast cell-specific histamine releasing activity in chronic idiopathic urticaria (CIU) . J Invest Dermatol. 1995;105:452. 92. Hide M, Francis DM, Grattan CEH, Barr RM, Winkelmann RK, Greaves MW. The pathogenesis of chronic idiopathic urticaria: new evidence suggests an autoimmune basis and implications for treatment . Clin Exp Allergy. 1994;24:624-627.Crossref 93. Hide M, Francis DM, Grattan CEH, Hakimi J, Kochan JP, Greaves MW. Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria . N Engl J Med. 1993;328:1599-1604.Crossref 94. Grattan CEH, Francis DM, Hide M, Greaves MW. Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria . Clin Exp Allergy. 1991;21:695-704.Crossref 95. Fiebiger E, Maurer D, Holub H, et al. Serum IgG autoantibodies directed against the alpha chain of Fc epsilon RI: a selective marker and pathogenetic factor for a distinct subset of chronic urticaria patients? J Clin Invest. 1995;96:2606-2612.Crossref 96. Hide M, Francis DM, Barr RM, Greaves MW. Skin mast cell activation by autoantibodies in urticaria and therapeutic implications . In: Kitamura Y, Yamamoto S, Galli SJ, Greaves MW, eds. Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function . New York, NY: Raven Press; 1995: 183-192. 97. Fiebiger E, Wichlas S, Stingl G, Maurer D. Autoantibodies directed against FcεRIα: IgG subtype composition, prevalence, and disease specificity . J Invest Dermatol. 1996;107:492. 98. Tong LJ, Balakrishnan G, Kochan JP, Kinét JP, Kaplan AP. Assessment of autoimmunity in patients with chronic urticaria . J Allergy Clin Immunol. 1997;99: 461-465.Crossref 99. Zweiman B, Valenzano M, Atkins PC, Tanus T, Getsy JA. Characteristics of histamine-releasing activity in the sera of patients with chronic idiopathic urticaria . J Allergy Clin Immunol. 1996;98:89-98.Crossref 100. Nawata Y, Koike T, Hosokawa H, Tomioka H, Yoshida S. Anti-IgE autoantibody in patients with atopic dermatitis . J Immunol. 1985;135:478-482. 101. Marone G, Casolaro V, Paganelli R, Quinti I. IgG anti-IgE from atopic dermatitis induces mediator release from basophils and mast cells . J Invest Dermatol. 1989; 93:246-252.Crossref 102. Grattan CEH, Francis DM, Slater NGP, Barlow RJ, Greaves MW. Plasmapheresis for severe, unremitting, chronic urticaria . Lancet. 1992;339:1078-1080.Crossref 103. O'Donnell BF, Barlow RJ, Kobza Black A, Greaves MW. Response of severe chronic urticaria to intravenous immunoglobulin (IVIG) . Br J Dermatol. 1994;131 ( (suppl 44) ):23.Crossref 104. O'Donnell BF, O'Neill CM, Welsh KI, Barlow RJ, Kobza Black A, Greaves MW. Is chronic urticaria an HLA-associated disease? Clin Exp Dermatol. 1995;20:271-272.Crossref 105. O'Donnell BF, Swana GT, Kobza Black A, Greaves MW. Organ and non organ specific auto-immunity in chronic urticaria . Br J Dermatol. 1995;133( (suppl 45) ): 42. 106. Barlow RJ, Kobza Black A, Greaves MW. Treatment of severe, chronic urticaria with cyclosporin A . Eur J Dermatol. 1993;3:273-275. 107. Haak-Frendscho M, Ridgway J, Shields R, Robbins K, Gorman C, Jardieu P. Human IgE receptor α-chain IgG chimera blocks passive cutaneous anaphylaxis reaction in vivo . J Immunol. 1993;151:351-358.

Brady, Mary S.;Coit, Daniel G.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440096014

Abstract The surgical treatment of patients with cutaneous melanoma has been revolutionized by the development of lymphatic mapping and sentinel lymph node biopsy. This procedure involves injecting a radioactive tracer at the site of the primary melanoma (before wide excision); the tracer then travels via the lymphatics to the first draining or sentinel lymph node. The node is removed and evaluated for the presence of metastatic melanoma. In this way, patients who are most likely to benefit can be selected for regional lymphadenectomy. In addition, accurate and minimally invasive staging allows the surgeon to identify patients who may benefit from adjuvant and investigational immunotherapy. We review the development of lymphatic mapping, the technical details related to the procedure itself, and the published clinical studies using this new procedure. In addition, we discuss the controversial issues that have been raised with the introduction of sentinel lymph node biopsy. Arch Dermatol. 1997;133:1014-1020 References 1. Sim FH, Taylor WF, Ivins JC, Pritchard DJ, Soule EH. A prospective randomized study of the efficacy of routine elective lymphadenectomy in management of malignant melanoma . Cancer. 1978;41:948-956.Crossref 2. Veronesi U, Adamus J, Bandiera DC, et al. Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities . Cancer. 1982;49: 2420-2430.Crossref 3. Balch CM, Soong SJ, Milton GW, et al. A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia . Ann Surg. 1982;196:677-684.Crossref 4. Balch CM, Murad TM, Soong SJ, Ingalls AL, Richards PC, Maddox WA. Tumour thickness as a guide to surgical management of clinical stage I melanoma patients . Cancer. 1979;43:883-888.Crossref 5. Milton GW, Shaw HM, McCarthy WH, Pearson L, Balch CM, Soong SJ. Prophylactic lymph node dissection in clinical stage I cutaneous malignant melanoma: results of surgical treatment in 1,319 patients . Br J Surg. 1982;69:108-111.Crossref 6. Balch CM, Soong SJ, Bartolucci AA, et al. Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger . Ann Surg. 1996;224:255-266.Crossref 7. Ross MI. The case for elective lymphadenectomy . Surg Oncol Clin N Am. 1992; 1:205-222. 8. Morton DL, Wen D-R, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma . Arch Surg. 1992;127:392-399.Crossref 9. Alex JC, Krag DN. Gamma-probe-guided localization of lymph nodes . Surg Oncol. 1993;2:137-144.Crossref 10. Uren RF, Howman-Giles RB, Shaw HM, Thompson JF, McCarthy WH. Lymphoscintigraphy in high-risk melanoma of the trunk: predicting draining node groups, defining lymphatic channels and locating the sentinel node . J Nucl Med. 1993; 34:1435-1440. 11. Uren RF, Howman-Giles RB, Thompson JF, Shaw HM, McCarthy WH. Lymphatic drainage from peri-umbilical skin to internal mammary nodes . Clin Nucl Med. 1995;20:254-255.Crossref 12. Krag DN, Meijer SJ, Weaver DL, et al. Minimal-access surgery for staging of malignant melanoma . Arch Surg. 1995;130:654-658.Crossref 13. Thompson JF, McCarthy WH, Bosch CMJ, et al. Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes . Melanoma Res. 1995;5:255-260.Crossref 14. Norman J, Cruse CW, Espinosa C, et al. Redefinition of cutaneous lymphatic drainage with the use of lymphoscintigraphy for malignant melanoma . Am J Surg. 1991;162:432-437.Crossref 15. Mudan A, Murray DR, Herda SC, et al. Early stage melanoma: lymphoscintigraphy, reproducibility of sentinel node detection, and effectiveness of the intraoperative gamma probe . Radiology. 1996;199:171-175.Crossref 16. Robinson DS, Sample WF, Fee HJ, Holmes EC, Morton DL. Regional lymphatic drainage in primary malignant melanoma of the trunk determined by colloidal gold scanning . Surg Forum. 1977;28:147-148. 17. Robinson DS, Sample WF, Fee JH, et al. Regional lymphatic drainage in primary malignant melanoma of the trunk determined by colloidal gold scanning . Surg Forum. 1977;28:147. 18. Morton DL, Wen D-R, Foshag LJ, Essner R, Cochran A. Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early-stage melanomas of the head and neck . J Clin Oncol. 1993;11:1751-1756. 19. Reintgen D, Cruse CW, Wells K, et al. The orderly progression of melanoma nodal metastases . Ann Surg. 1994;220:759-767.Crossref 20. Alex JC, Weaver DL, Fairbank JT, Rankin BS, Krag DN. Gamma-probe-guided lymph node localization in malignant melanoma . Surg Oncol. 1993;2:303-308.Crossref 21. van der Veen H, Hoekstra OS, Paul MA, Cuesta MA, Meijer S. Gamma probe-guided sentinel node biopsy to select patients with melanoma for lymphadenectomy . Br J Surg. 1994;81:1769-1770.Crossref 22. Pijpers R, Collet GJ, Meijer S, Hoekstra OS. The impact of dynamic lymphoscintigraphy and gamma probe guidance on sentinel node biopsy in melanoma . Eur J Nucl Med. 1995;22:1238-1241.Crossref 23. Glass LF, Fenske NA, Messina JL, et al. The role of selective lymphadenectomy in the management of patients with malignant melanoma . Dermatol Surg. 1995; 21:979-983. 24. Balch CM. The role of elective lymph node dissection in melanoma: rationale, results, and controversies . J Clin Oncol. 1988;6:163-172. 25. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684 . J Clin Oncol. 1996;14: 7-17. 26. Buzaid AC, Sandler AB, Mani S, et al. Role of computed tomography in the staging of primary melanoma . J Clin Oncol. 1993;11:639-643. 27. Kuvshinoff BW, Kurtz C, Coit DG. Computed tomography in the evaluation of patients with stage III melanoma . Ann Surg Oncol. 1997;43:252-258.Crossref 28. Fisher ER, Swamidoss S, Lee CH, Rockette H, Redmond C, Fisher B. Detection and significance of occult axillary node metastases in patients with invasive breast cancer . Cancer. 1978;42:2025-2031.Crossref 29. Wells CA, Heryet A, Brochier J, Gatter KC, Mason DY. The immunohistochemical detection of axillary micrometastases in breast cancer . Br J Cancer. 1984; 50:193-197.Crossref 30. Cochran AJ, Wen D-R, Morton DL. Occult tumor cells in lymph nodes of patients with pathological stage I malignant melanoma: an immunohistological study . Am J Surg Pathol. 1988;12:612-618.Crossref 31. Heller R, Becker J, Wasselle J, et al. Detection of submicroscopic lymph node metastases in patients with melanoma . Arch Surg. 1991;126:1455-1460.Crossref 32. Wang X, Heller R, VanVoorhis N, et al. Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma . Ann Surg. 1994;220:768-774.Crossref

Harden, Danvid;Keeling, James H.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440109015pmid: 9267250

Abstract REPORT OF A CASE A previously healthy 39-year-old black man presented with a 4-month history of multiple papular and nodular lesions on his scalp, face, and neck, as well as painful lesions in his mouth and on his tongue. About a month before this eruption occurred, the patient experienced swelling of the right side of his neck; the swelling was associated with headache, sore throat, earache, arthralgia, sweats, and temperatures ranging from 38°C to 39°C, all of which lasted around 3 weeks. Several weeks before these symptoms developed, the patient had noticed a painless penile lesion.Examination revealed multiple flesh-colored to red-brown papules and nodules located on the face, neck, scalp, and nares (Figure 1). Several nodules had a crusted surface. White patches were noticed on the palate, tongue, and lips. There were collarettes of scale on both palms. Bilateral, tender adenopathy was found in the cervical, axillary, References 1. Lejman K, Starzycki Z. Keratopustular variety of framboesiform syphilis: a case report . Br J Venereol Dis. 1977;53:195-199. 2. Beck MH, Hubbard HC, Dave VK, Haye KR. Secondary syphilis with framboesiform facial lesions: a case report . Br J Venereol Dis. 1981;56:103-105. 3. Graham WR Jr, Duvic M. Nodular secondary syphilis . Arch Dermatol. 1982;118: 205-206.Crossref 4. Baum EW, Bernhardt M, Sams WM Jr, Alexander WJ, McLean GL. Secondary syphilis: still the great imitator . JAMA. 1983;249:3069-3070.Crossref 5. Matsuda-John SS, McElgunn PSJ, Ellis CN. Nodular late syphilis . J Am Acad Dermatol 1983;9:269-272.Crossref 6. Hodak E, David M, Rothem A, Bialowance M, Sandback M. Nodular secondary syphilis mimicking cutaneous lymphorecticular process . J Am Acad Dermatol. 1987;17(pt (2) ):914-917.Crossref 7. Tham SN, Ng SK. Secondary syphilis with framboesiform lesions . Genitourin Med. 1990;66:99-100. 8. Pavithran K. Nodular secondary syphilis . Int J Dermatol. 1991;30:799-800.Crossref 9. Adriaans B. An erythematous nodular eruption. Secondary syphilis . Arch Dermatol. 1992;128:978-981.Crossref 10. Jeerapaet P, Ackerman AB. Histologic patterns of secondary syphilis . Arch Dermatol. 1973;107:373-377.Crossref 11. Abell E, Marks R, Jones EW. Secondary syphilis: a clinico-pathological review . Br J Dermatol. 1975;93:53-61.Crossref 12. Hook EW, Marra CM. Acquired syphilis in adults . N Engl J Med. 1992;326:1060-1069.Crossref

Merkert, Ralf

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440111016pmid: 9267251

Abstract REPORT OF A CASE A 54-year-old, alcoholic, black woman presented with a 1-month history of papular lesions on her face, trunk, and limbs that had progressed to pustules and painful ulcers. Physical examination revealed pleomorphic skin lesions of the face, trunk, arms, and mucous membrane of the mouth. Morphologically, papules, pustules, and superficial and deep crusted ulcers were evident (Figure 1). The ulcers had well-defined erythematous edges without undermining (Figure 2). A biopsy specimen was obtained (Figure 3 and Figure 4).What is your diagnosis? DIAGNOSIS: Noduloulcerative syphilis (malignant syphilis, lues maligna). HISTOPATHOLOGIC FINDINGS The biopsy specimen of an intact papule demonstrated a superficial and deep perivascular mixed infiltrate with lymphocytes, plasma cells, and epithelioid giant cells forming loose noncaseating granulomas throughout the dermis (Figures 3 and 4). Stains were negative for fungi, mycobacteria, and spirochetes. CLINICAL COURSE Results of a VDRL References 1. Cripps DJ, Curtis AC. Syphilis maligna praecox: syphilis of the great epidemic? an historical review . Arch Intern Med. 1967;119:411-418.Crossref 2. Rufli T. Syphilis and HIV infection . Dermatologica. 1989;179:113-117.Crossref 3. Held JL, Ross M, Beltrani V, Kohn SR, Grossman ME. Noduloulcerative or 'malignant' syphilis occurring in an otherwise healthy woman: report and review of a dramatic dermatosis . Cutis. 1990;45:119-122. 4. Lejman K, Starzycki Z. Syphilis maligna praecox: a case report . Br J Venereol Dis. 1972;48:194-199. 5. Shulkin D, Tripoli L, Abell E. Lues maligna in a patient with human immunodeficiency virus infection . Am J Med. 1988;85:425-427.Crossref 6. French CH. Malignant syphilis . J R Army Med Corp. 1905;4:477-487. 7. Bahmer FA, Anton-Lamprecht L. Ultrastructural features of malignant syphilis and demonstration of Treponema pallidum . Int J Dermatol. 1983;22:165-170.Crossref 8. Fisher DA, Chang LW, Tuffanelli DL. Lues maligna: presentation of a case and a review of the literature . Arch Dermatol. 1969;99:70-73.Crossref 9. Hasland A. Syphilis maligna . Arch Dermatol Syphilol. 1897;38:345-392. 10. Petrozzi JW, Lockshin NA, Berger BJ. Malignant syphilis: severe variant of secondary syphilis . Arch Dermatol. 1974;109:387-389.Crossref 11. Schröter R, Näher H, Petzoldt D. Hautmanifestationen der Syphilis maligna bei HIV-Infektion: Klinische Beobachtung an drei Fällen . Hautarzt. 1988;39:463-466.

Miquel, F.Javier;Vilata, JuanJ.;Gil, M. Pino;Chofre, Carmen

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440113017

Abstract REPORT OF A CASE A 28-year-old woman presented with a 3-year history of symptomless erythematous macular cutaneous lesions. These macules coalesced into large patches with geographic edges and were located mainly on the trunk and proximal surface of the extremities. Their distribution was nearly symmetrical. Skin folds were spared (Figure 1 and Figure 2). Initially, the lesions were small and almost undiscernible, but they progressively increased in size and number and became confluent. On examination, no infiltration was noted and sensation was not reduced.The patient was in otherwise general good health. Her physical examination and laboratory tests, including a complete blood cell count, serum biochemistry workup, urinalysis, and chest radiography, revealed no abnormalities.An excisional biopsy specimen was obtained from a lesion located on the trunk (Figure 3 and Figure 4). What is your diagnosis? DIAGNOSIS: Lepromatous leprosy, macular stage. H1STOPATHOLOGIC FINDINGS AND CLINICAL COURSE Hematoxylin-eosin-stained sections showed no epidermal changes. A dermal cellular infiltrate was noted, References 1. Who Expert Committee on Leprosy . World Health Organ Tech Rep Ser. 1988; 768:1-51. 2. Ridley DS, Jopling WH. Classification according to immunity . Int J Lepr. 1966; 34:255. 3. McDougall AC, Ulrich MI. Mycobacterial disease: leprosy . In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds. Dermatology in General Medicine. 4th ed. New York, NY: McGraw-Hill Inc; 1993:2395-2410. 4. García Pérez A. La endemia de lepra y la lucha antileprosa en España. Piel. 1989; 4:56-59. 5. Olivier HR. Psychiatric aspects of Hansen's disease (leprosy) . J Clin Psychiatry. 1987;48:477-479.

Artüz, Ferda;Alli, Nuran;Lenk, Nurdan;Güngör, Emel

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440115018pmid: 9267253

Abstract REPORT OF A CASE A 20-year-old woman had painless, purple, erythematous, plaquelike lesions of 7 years' duration. At the time of presentation, she was 7 months pregnant. She had no medical problems other than the skin lesions. She denied any trauma to the affected areas.Physical examination revealed a 5×6-cm, purple, irregularly bordered plaque on the dorsal aspect of her left arm (Figure 1) and a 10×8-cm, slightly crusted and ulcerated, erythematous, psoriasiform lesion on the left side of her face. The results of routine laboratory tests were unremarkable. A punch biopsy specimen was obtained from the lesion on the left side of her face (Figure 2).What is your diagnosis? DIAGNOSIS: Chromomycosis. HISTOPATHOLOGIC FINDINGS AND CLINICAL COURSE There was a granulomatous reaction containing giant cells and mononuclear inflammatory infiltration around the granuloma. Brown spherical bodies with dark cell walls were evident in the cytoplasm of the giant cells and in the extracellular portion; these organisms stained References 1. Tufanelli L, Milburn PB. Treatment of chromoblastomycosis . J Am Acad Dermatol. 1990;23:728-732.Crossref 2. Gross DJ, Schosser RH. Chromomycosis on the nose . Arch Dermatol. 1991; 127:1831-1835.Crossref 3. Milliam CP, Fenske NA. Chromoblastomycosis . Dermatol Clin. 1989;7:219-225. 4. Rubin HA, Bruce S, Rosen T. Evidence for percutaneous inoculation as the mode of transmission for chromoblastomycosis . J Am Acad Dermatol. 1991;25:951-954.Crossref 5. Paradinaud R, Bolzinger T. Treatment of chromoblastomycosis . J Am Acad Dermatol. 1991;25(pt (1) ):869-870.Crossref

Cramer, Stewart F.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440117019

Abstract IN THIS issue of the Archives, 2 articles address the issue of interobserver variability in diagnostic pathology. Although such studies have been done for several decades, this field is only recently beginning to mature toward a systematic discipline with standardized principles and methods. It is still in a somewhat embryonic state. This editorial will address the general issue of interobserver variability and then analyze these 2 papers. GENERAL COMMENTS When there is interobserver variability in diagnostic pathology, it raises complex and emotional issues. The first reaction is usually to ask, "Who's right?"1 After all, a clear and reliable pathology report is needed to guide the management of the patient. Patient care must always be the first concern. The immediate corollary, "Who's wrong?" may raise questions about reliability and convey feelings of anxiety and distrust. If variability is common, especially among experts in research projects, there may be opinions that diagnostic References 1. Cramer SF, Roth LM, Ulbright TM, et al. The mystique of the mistake: with proposed standards for validating proficiency tests in anatomic pathology . Am J Clin Pathol. 1991;96:774-777. 2. Cramer SF, Roth LM, Ulbright TM, et al. Evaluation of the reproducibility of the World Health Organization classification of common ovarian cancers: with emphasis on methodology . Arch Pathol Lab Med. 1987;111:819-829. 3. Cramer SF, Roth LM, Mills SE, et al. Sources of variability in classifying common ovarian cancers using the World Health Organization classification: application of the Pathtracking method . Pathol Annu. 1993;28:243-286. 4. Cramer SF. Interobserver variability in surgical pathology . Adv Pathol. 1996;9: 3-82. 5. National Cancer Institute's Non-Hodgkin's Classification Project Writing Com- mittee. Classification of non-Hodgkin's lymphomas: reproducibility of major classification systems . Cancer. 1985;55:91-95.Crossref 6. Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group . Blood. 1994;84:1361-1392. 7. Scully RE. The need for uniform terminology . Human Pathol. 1973;4:602-603.Crossref 8. ten Seldam REJ, Helwig EB, Sobin LH, Torloni H. Histological Typing of Skin Tumours, International Histological Classification of Tumours , No. (12) . Geneva, Switzerland: World Health Organization; 1974:9-10. 9. NIH Consensus Development Panel. Diagnosis and treatment of early melanoma . JAMA. 1992;268:1314-1319.Crossref 10. NIH Consensus Conference. Precursors to malignant melanoma . JAMA. 1984; 251:1864-1866.Crossref 11. Barnhill RL. Pathology of Melanocytic Nevi and Malignant Melanoma . Newton, Mass: Butterworth-Heinemann; 1995:169-194. 12. Clark WH Jr, Reimer RR, Greene M, et al. Origin of familial melanomas from heritable melanscytic lesions: the 'B-K mole syndrome.' Arch Dermatol. 1978;114: 732-738.Crossref 13. Elder DE, Murphy GF. Melanocytic tumors of the skin . In: Atlas of Tumor Pathology . Fascicle 2, 3rd series. Washington, DC: Armed Forces Institute of Pathology; 1990:78-102. 14. Seab JA Jr. Dysplastic nevi and the dysplastic nevus syndrome . Dermatol Clin. 1992;10:189-201.Crossref 15. Webster's Encyclopedic Unabridged Dictionary of the English Language . New York, NY: Gramercy Books; 1989:64. 16. Duray PH, Dersimonian R, Barnhill RL, et al. An analysis of interobserver recognition of the histopathologic features of dysplastic nevi from a mixed group of nevomelanocytic lesions . J Am Acad Dermatol. 1992;27:741-749.Crossref 17. deWit PE, van't Hof-Grootenboer B, Ruiter DJ, et al. Validity of the histopathological criteria used for diagnosing dysplastic naevi: an interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group . Eur J Cancer. 1993;29A:831-839.Crossref 18. Duncan LM, Berwisk M, Bruijn JA, et al. Histopathologic recognition and grading of dysplastic melanocytic nevi: an interobserver agreement study . J Invest Dermatol. 1993;100:318S-321S.Crossref 19. Piepkorn MW, Barnhill RL, Cannon-Albright LA, et al. A multiobserver populationbased analysis of histologic dysplasia in melanocytic nevi . J Am Acad Dermatol. 1994;30:707-714.Crossref 20. Carroll L. Alice's Adventures in Wonderland and Through the Looking Glass . Philadelphia, Pa: John C. Winston Co; 1923: chap 6 . 21. Weinstock MA, Barnhill RL, Rhodes AR, Brodsky GL, and the Dysplastic Nevus Panel. Reliability of the histopathologic diagnosis of melanocytic dysplasia . Arch Dermatol. 1997;133:953-958.Crossref 22. Horn TD, Zahurak ML, Atkins D, Solomon AR, Vogelsang GB. Lichen planus-like cutaneous graft-vs-host reaction: prognostic significance independent of time course after allogeneic marrow transplantation . Arch Dermatol. 1997;133:961-965.Crossref 23. Smoller BR, Egbert BM. Dysplastic nevi can be diagnosed and graded reproducibly: a longitudinal study . J Am Acad Dermatol. 1992;27:399-402.Crossref 24. Batts KP, Ludwig J. Chronic hepatitis: an update on terminology and reporting . Am J Surg Pathol. 1995;19:1409-1417.Crossref 25. Rickert RE. Quality assurance goals in surgical pathology . Arch Pathol Lab Med. 1990;114:1157-1162. 26. Association of Directors of Anatomic and Surgical Pathology. Consultations in surgical pathology . Mod Pathol. 1992;5:567-568. 27. Lieblich LM. On making a histologic diagnosis: are explicit criteria always necessary to make a correct diagnosis? Am J Dermatopathol. 1980;2:349-356.Crossref 28. Dalton LW, Page DL, Dupont WD. Histologic grading of breast carcinomas: a reproducibility study . Cancer. 1994;73:2765-2770.Crossref 29. Henson DE. End points and significance of reproducibility in pathology . Arch Pathol Lab Med. 1989;113:830-831.

Myskowski, Patricia L.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440123020

Abstract WITH THE eradication of smallpox, molluscum contagiosum (MC) virus (MCV) became the last remaining member of the Poxviridae family to specifically infect humans.1-3 Unlike the related poxviruses variola and vaccinia, MCV received little attention, since infection resulted in benign cutaneous neoplasms that were usually self-limited or easily controlled. All that changed with the advent of the acquired immunodeficiency syndrome (AIDS), as extensive and recalcitrant MC emerged as an important cause of morbidity and disfigurement.4-8 Physicians who treat MC in human immunodeficiency virus (HIV)— infected individuals have been frustrated by the lack of effective antiviral therapy and the inexorable progression of MC lesions as patients enter the late stages of HIV disease.5,6,8 Fortunately, recent basic knowledge about poxviruses, through sequencing of the MCV genome,9 as well as advances in the therapy of HIV-infected patients,10,11 gives reasons for optimism. Poxviruses wereamong the first groups of infectious agents to be morphologically defined by their effect References 1. Buller RML, Palumbo GJ. Poxvirus pathogenesis . MicrobiolRev. 1991;55:80-122. 2. Moss B. Poxviridae and their replication . In: Fields BN, Knipe DM, Melnick JL, et al, eds. Virology. 2nd ed. New York, NY: Raven Press; 1990:chap 74. 3. Fenner F. Poxviruses . In: Fields BN, Knipe DM, Melnick JL, et al, eds. Virology. 2nd ed. New York, NY: Raven Press; 1990:chap 75. 4. Lombardo PC. Molluscum contagiosum and the acquired immunodeficiency syndrome . Arch Dermatol. 1985;121:834-835.Crossref 5. Schwartz JJ, Myskowski PL. Molluscum contagiosum in patients with human immunodeficiency virus infection: a review of twenty-seven patients . J Am Acad Dermatol. 1992;27:583-588.Crossref 6. Koopman RJJ, Van Merrien boer FCJ, Vreden SGS, Dolmans WMV. Molluscum contagiosum: a marker for advanced HIV infection . Br J Dermatol. 1992;126:528-529.Crossref 7. Gottlieb SL, Myskowski PL. Molluscum contagiosum . Int J Dermatol. 1994;33: 453-461.Crossref 8. Cronin TA, Resnik BI, Elgart G, et al. Recalcitrant giant molluscum contagiosum in a patient with AIDS. J Am Acad Dermatol. 1996;35:266-267.Crossref 9. Senkevich TG, Bugert JJ, Sisler JR, Koonln EV, Darai G, Moss B. Genome sequence of a human tumorigenic poxvirus: prediction of specific host responseevasion genes . Science. 1996;273:813-816.Crossref 10. Bartlett JG. Protease inhibitors for HIV infection . Ann Intern Med. 1996;124: 1086-1088.Crossref 11. Deeks SG, Smith M, Holodniy M, Kahn JO. HIV-1 protease inhibitors: a review for clinicians . JAMA. 1997;277:145-153.Crossref 12. Porter CD, Archard LC. Characterization and physical mapping of molluscum contagiosum virus DNA and location of a sequence capable of encoding a conserved domain of epidermal growth factor . J Gen Virol. 1987;68:673-682.Crossref 13. Viac J, Chardonnet Y. Immunocompetent cells and epithelial cell modifications in molluscum contagiosum . J Cutan Pathol. 1990;17:202-205.Crossref 14. Douglas JD, Tanner KN, Prine JR, van Riper DC, Derwells SK. Molluscum contagiosum in chimpanzees . J Am Vet Med Assoc. 1967;151:901-904. 15. Bagnall BG, Wilson GR. Molluscum contagiosum in a red kangaroo . Australas J Dermatol. 1974;15:115-118.Crossref 16. Van Rensburg IB, Collett MG, Ronen N, Gerdes T. Molluscum contagiosum in a horse . J S Afr Vet Assoc. 1991;62:72-74. 17. Buller RM, Burnett J, Chen W, Kreider J. Replication of molluscum contagiosum virus . Virology. 1995;213:655-659.Crossref 18. Fife KH, Whitfield M, Faust H, Goheen MP, Bryan J, Brown DR. Growth of a molluscum contagiosum virus in a human foreskin xenograft model . Virology. 1996; 226:95-101.Crossref 19. Pinkus H, Frisch D. Inflammatory reactions to molluscum contagiosum, possibly of immunologic nature . J Invest Dermatol. 1949;13:289-294.Crossref 20. Reed RJ, Parkinson RP. The histogenesis of molluscum contagiosum . Am J Surg Pathol. 1977;1:161-166.Crossref 21. Weinberg JM, Mysliwiec A, Turiansky GW, Redfield R, James WD. Viral folliculitis: atypical presentations of herpes simplex, herpes zoster, and mollusum contagiosum . Arch Dermatol. 1997;133:983-986.Crossref 22. Heng MCY, Steuer ME, Levy A, et al. Lack of host cellular immune response in eruptive molluscum contagiosum . Am J Dermatopathol. 1989;11:248-254.Crossref 23. Bhawan J, Dayal Y, Bhan AK. Langerhans cells in molluscum contagiosum, verruca vulgaris, plantar wart, and condyloma acuminatum . J Am Acad Dermatol. 1986;15:646-649.Crossref 24. Shelley WB, Burkmeister V. Demonstration of a unique viral structure: the molluscum viral colony sac . Br J Dermatol. 1986;115:557-562.Crossref 25. Steffen C, Markman J. Spontaneous disappearance of molluscum contagiosum . Arch Dermatol. 1980;116:923-924.Crossref 26. Henao M, Freeman RG. Inflammatory molluscum contagiosum: clinicopathological study of seven cases . Arch Dermatol. 1964;90:479-482.Crossref 27. Charteris DG, Bonshek, Tullo AB. Ophthalmic molluscum contagiosum: clinical and immunopathological features . Br J Ophthalmol. 1995;79:476-481.Crossref 28. Pauly CR, Artis WM, Jones HE. Atopic dermatitis, impaired cellular immunity, and molluscum contagiosum . Arch Dermatol. 1978;114:391-393.Crossref 29. Slawsky LD, Gilson RT, Hockley AJ, Libow LF. Epidermodysplasia verruciformis associated with severe immunodeficiency . J Am Acad Dermatol. 1992;27:448-456.Crossref 30. Mayuma H, Yamaoka K, Tsutsui T, et al. Selective immunoglobulin M deficiency associated with disseminated molluscum contagiosum . Eur J Pediatr. 1986;145: 99-103.Crossref 31. Cotton DWK, Cooper C, Barrett DF, Leppard BJ. Severe atypical molluscum contagiosum infection in an immunocompromised host . Br J Dermatol. 1987;116: 871-876.Crossref 32. Smith DK, Neal JJ, Holmberg SD, and the Centers for Disease Control Idiopathic CD4+ T-Lymphocytopenia Task Force. Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV infection: an investigation in the United States . N Engl J Med. 1993;328:373-379.Crossref 33. Spira TJ, Jones BM, Nicholson JKA, et al. Idiopathic CD4+ T-lymphocytopenia: four patients with opportunistic infections and no evidence of HIV infection . N Engl J Med. 1993;328:386-392.Crossref 34. Telner P, Solomon LM. Eruptive molluscum contagiosum in atopic dermatitis . Can Med Assoc J. 1966;95:978-979. 35. Hellier FF. Profuse mollusca contagiosa of the face induced by corticosteroids . Br J Dermatol. 1971;85:398.Crossref 36. Rosenberg EW, Yusk JW. Molluscum contagiosum: eruption following treatment with prednisone and methotrexate . Arch Dermatol. 1970;101:439-441.Crossref 37. Reynaud-Mendel B, Janier M, Gerbaka J, et al. Dermatologic findings in HIV-1— infected patients: a prospective study with emphasis in CD4+ cell count . Dermatology. 1996;192:325-328.Crossref 38. Goldstein B, Berman B, Sukenik E, Frankel SJ. Correlation of skin disorders with CD4 lymphocyte count in patients with HIV/AIDS . J Am Acad Dermatol. 1997; 36:262-264.Crossref 39. Smith KJ, Skelton HG, Yeager J, et al. Molluscum contagiosum: ultrastructural evidence for its presence in skin adjacent to clinical lesions in patients infected with human immunodeficiency virus type 1 . Arch Dermatol. 1992;128:223-227.Crossref 40. Belsito DV, Sanchez MR, Baer RL, et al. Reduced Langerhans' cell la antigen and ATPase activity in patients with the acquired immunodeficiency syndrome . N Engl J Med. 1984;310:1279-1282.Crossref 41. Fivenson DP, Weltman RE, Gibson SH. Giant molluscum contagiosum presenting as basal cell carcinoma in an acquired immunodeficiency syndrome patient . J Am Acad Dermatol. 1988;19:912-914.Crossref 42. Schwartz JJ, Myskowski PL. HIV-related molluscum contagiosum presenting as a cutaneous horn . Int J Dermatol. 1992;31:142-144.Crossref 43. Smith KJ, Skelton HG, Yeager J, et al. Histopathologic and immunohistochemical findings associated with inflammatory dermatoses in human immunodeficiency virus type 1 disease and their correlation with Walter Reed stage . J Am Acad Dermatol. 1993;28:174-184.Crossref 44. Meadows KP, Tyring SK, Pavia AT, Rallis TM. Resolution of recalcitrant molluscum contagiosum virus lesions in human immunodeficiency virus-infected patients treated with cidofovir . Arch Dermatol. 1997;133:987-990.Crossref 45. Garrett SJ, Robinson JK, Roenigk HH. Trichloracetic acid peel of molluscum contagiosum in immunocompromised patients . J Dermatol Surg Oncol. 1992;18: 855-858.Crossref 46. Funt TR. Catharidin treatment of molluscum contagiosum . Arch Dermatol. 1961; 83:504-505.Crossref 47. Syed TA, Lundin S, Ahmad M. Topical 0.3% and 0.5% podophyllotoxin cream for self-treatment of molluscum contagiosum in males . Dermatology . 1994;189: 65-68.Crossref 48. Moss B, Rosenblum EN, Katz E, Grimley PM. Rifampicin: a specific inhibitor of vaccinia virus assembly . Nature. 1969;224:1280-1284.Crossref 49. Kane EM, Shuman S. Adenosine N1-oxide inhibits vaccinia virus replication by blocking translation of viral early mRNAS . J Virol. 1995;69:6352-6358. 50. Murphy M, Armstrong, DA Sepkowitz KA, Ahkami R, Myskowski PL. Regression of AIDS-related Kaposi's sarcoma following treatment with an HIV-1 protease inhibitor . AIDS. 1997;11:261-262.

Cruz, Ponciano D.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440129021

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables. Abstract THE ANNUAL Trainee Award is given to the dermatology resident, fellow, or student who was first author on the most meritorious original research article published in the Archives in a given year. Letters of nomination for trainee first authors may be submitted throughout the year by senior authors, research preceptors, or training directors. Formal announcement of the award is made at the Residents' Colloquium, held at the annual meeting of the American Academy of Dermatology. To allow closer synchrony between the judging process and formal announcement, the annual time frame for consideration has been moved from December to October. Thus, the 1997 recipient will be chosen from among nominations corresponding to articles published in the Archives from January to October 1997. Thereafter, the annual awardee will be chosen from nominations corresponding to articles published from November of the previous year to October of the following year.

Bernhard, Jeffrey D.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440133024pmid: 9267257

Abstract I was intrigued by the discovery of anti-basement membrane zone antibodies in healthy elderly individuals as reported by Hachisuka and colleagues1 because of the theoretical possibility that such antibodies could play a role in so-called senile pruritus. In most cases of itching in the elderly, a cause, such as medication use, xerosis, skin disease, or underlying systemic illness, can be identified. By definition, the cause of senile pruritus is officially unknown,2 although some cases may have an age-related neurologic basis.3 Itching without a rash, itching with erythema or urticarial plaques but without blisters, and generalized pruritus with secondary lesions but without blisters are recognized prodromes or presentations of pemphigoid.4,5 Perhaps some cases of senile pruritus are the consequence of anti-basement membrane zone antibody formation, stuck qualitatively or quantitatively at some point between nonbinding with no disease and the point at which binding sufficient to cause frank bullous References 1. Hachisuka H, Kurose K, Karashima T, et al. Serum from normal elderly individuals contains anti-basement membrane zone antibodies . Arch Dermatol. 1996;132:1201-1205.Crossref 2. Bernhard JD. Itch: Mechanisms and Management of Pruritus . New York, NY: McGraw-Hill Book Co; 1994:56-57. 3. Bernhard JD. Phantom itch, pseudophantom itch, and senile pruritus . Int J Dermatol. 1992;31:856-857.Crossref 4. Barriere H, Bureau B, Welin J, et al. Prurit 'sine materia' et pemphigoide bulleuse . Ann Dermatol Venereol. 1981;108:445-448. 5. Bingham EA, Burrows D, Sandford JC. Prolonged pruritus and bullous pemphigoid . Clin Exp Dermatol. 1984;9:564-570.Crossref

Sybert, Virginia P.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440133022pmid: 9267256

Abstract I read with great interest the article by Luther and colleagues in a recent issue of the Archives1 reviewing their herculean analysis of the development of melanocytic nevi over time in children. However, the authors presented no information regarding patients' family histories of melanocytic nevi. Although Luther et al looked at predisposing risk factors that may be genetic in origin, eg, hair color and skin color, they did not appear to evaluate what is probably the single most important factor in regard to the development of nevi: the presence of nevi in a parent. My second concern is whether there is any correlation between the number of nevi at the first visit and the number developed over time. In other words, do children who have greater numbers of nevi in early childhood have a higher risk to develop even proportionately greater numbers over time, or is sun exposure itself References 1. Luther H, Altmeyer P, Garbe C, et al. Increase of melanocyte nevus counts in children during 5 years of follow-up and analysis of associated factors . Arch Dermatol. 1996;132:1473-1478.Crossref

Luther, Heike;Garbe, Claus;Altmeyer, Peter

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440133023

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables. Abstract Sybert hits on an important factor for nevus development that was not carefully enough considered in our study. Additionally, it undoubtedly would be a doubly herculean work to count the nevi not only in children but also in their parents. Future studies, however, should take the numbers of nevi of the parents into consideration because this might be an additional important risk factor for the development of nevi in children. Concerning the second issue, we reevaluated our data. Introducing the number of nevi at first visit into our logistic model, we found that this was the factor predicting the increase of melanocytic nevus counts with the highest significance (P<.001). Additionally, variables regarding sun exposure were still significantly related to the increase in the number of melanocytic nevi (Table) The skin type, however, was no longer a significant factor if the number of melanocytic nevi at first examination of the children

Lebbé, Celeste;Agbalika, Félix

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440134026

Abstract We thank Drago and Reborafor their interest in our work. They state that the hypothesis drawn from our data, which suggests that there could be a link between human herpesvirus (HHV) 8 detection in peripheral blood mononuclear cells and clinical staging of Kaposi sarcoma, is contrary to all that is known of HHV biological behavior. They rely on data concerning 2 HHVs, HHV-6 and HHV-7, which, to our knowledge, have not been consistently associated with any human neoplastic disease and, as far as HHV-7 is concerned, to any human disease. The statement by Drago and Rebora regarding our hypothesis seems rather hazardous considering that various data suggest alink between HHV viremia in the peripheral blood mononuclear cells and either the severity or the duration of the disease. For instance, the presence of a larger amount of mononuclear cells infected with HHV-6 correlates with a longer rash phase in infants with exanthema subitum. References 1. Asano Y, Nakashima T, Yoshikawa T, Suga S, Yazaki T. Severity of human herpesvirus-6 viremia and clinical findings in infants with exanthem subitum . J Pediatr. 1991;118:891-895.Crossref 2. Yao QY, Rickinson AB, Epstein MA. A re-examination of the Epstein-Barr virus carrier state in healthy seropositive individuals . Int J Cancer. 1985;35:35-42.Crossref 3. Saltzman RL, Quirk MR, Jordan MC. High levels of circulating cytomegalovirus DNA reflect visceral organ disease in viremic immunosuppressed patients other than marrow recipients . J Clin Invest. 1992;90:1832-1838.Crossref 4. Brambilla L, Boneschi V, Berti E, Corbellino M, Parravicini C. HHV8 cell-associated viraemia and clinical presentation of Mediterranean Kaposi's sarcoma . Lancet. 1996;347:1338.Crossref 5. Grandadam M, Dupin N, Calvez V, et al. Exacerbations of clinical symptoms in human immunodeficiency virus type 1—infected patients with multicentric Castleman's disease are associated with a high increase in Kaposi's sarcoma herpesvirus DNA load in peripheral blood mononuclear cells . J Infect Dis. 1997;175:1198-1201.Crossref 6. Lebbé C, Tatoud R, Morel P, et al. Human herpesvirus 8 sequences are not detected in epithelial tumors from patients receiving transplants . Arch Dermatol. 1997;133:111. 7. Lebbé C, Pellet C, Flageul B, et al. Sequences of human herpesvirus 8 are not detected in various non—Kaposi sarcoma vascular lesions . Arch Dermatol. 1997; 133:919-920.Crossref

Drago, Francesco;Rebora, Alfredo

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440134025

Abstract The statement by Lebbé et al1 that the detection of human herpesvirus (HHV) 8 sequences in peripheral blood mononuclear cells (PBMCs) of patients with Kaposi sarcoma (KS) is related to the tumor burden seems hazardous. This conclusion is contrary to all we know of HHV biological behavior. For none of the HHVs has the amount or even the existence of latently infected cells been correlated with a clinical disease or viral diffusion in other tissues. Indeed, some, if not all, of the known HHVs are carried by PBMCs in healthy individuals. For example, in Italy, using polymerase chain reaction (PCR), we recently detected HHV-7 DNA sequences in PBMCs in 11 (44%) of 25 healthy individuals.2 As for HHV-8, its sequence has been detected in the blood of healthy individuals. This virus is so widespread that in the American population approximately 25% of adults and 2% to 8% of children References 1. Lebbé C, Agbalika F, de Crémoux P, et al. Detection of human herpesvirus 8 and human T-cell lymphotropic virus type 1 sequences in Kaposi sarcoma . Arch Dermatol . 1997;133:25-30.Crossref 2. Drago F, Ranieri E, Malaguti F, Losi E, Rebora A. Human herpesvirus 7 in pityriasis rosea . Lancet . 1997;349:1367-1368.Crossref 3. Zhong W, Wang H, Herndier B, Ganem D. Restricted expression of Kaposi sarcoma—associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma . Proc Natl Acad Sci USA . 1996;93:6641-6646.Crossref 4. Carrigan DR. Human herpesvirus-6 and bone marrow transplantation . Blood . 1995;85:294-295. 5. Lusso P, Ensoli B, Markham PD, et al. Productive dual infection of human CD4+ T lymphocytes by HIV-1 and HHV-6 . Nature . 1989;337:370-373.Crossref 6. Henghold WB II, Purvis SF, Schaffer J, Leonard DGB, Giam C-Z, Wood GS. Kaposi sarcoma—associated herpesvirus/human herpesvirus type 8 and Epstein-Barr virus in iatrogenic Kaposi sarcoma . Arch Dermatol . 1997;133:109-111.Crossref

Depaire-Duclos, Florence;Gris, Jean Charles;Dandurand, Michel;Guillot, Bernard

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440135027

Abstract Five major inherited disorders are considered risk factors for recurrent venous thrombosis: protein C, protein S, or antithrombin III deficiency, hyperhomocystinemia, and activated protein C (APC) resistance. In 1993, Dahlbäck1 noted that the addition of APC to plasma obtained from a patient with recurrent thrombosis, without any previously recognized thrombotic disorder, did not prolong the activated partial thromboplastin time as occurred when APC was added to plasma from healthy individuals. The term APC resistance was used to describe this patient. Most patients with APC resistance have a mutant factor V molecule (Leiden mutation) that resists proteolysis by APC when activated to factor Va. This resistance is the result of a specific point mutation (replacement of arginine 506 by glutamine) in the gene coding for coagulation factor V. Not all patients with APC resistance will experience thrombosis. Additional genetic defects or exogenous factors may be necessary to induce thrombosis in References 1. Dahlbäck B. Molecular genetics of thrombophilia: factor V gene mutation causing resistance to activated protein C as a basis of the hypercoagulable state . J Lab Clin Med. 1995;125:566-571. 2. Rodgers GM. Activated protein C resistance and inherited thrombosis . Am J Clin Pathol. 1995;103:261-262. 3. Hesse S, Berbis S, Juhan-Vague I, et al. Syndrome de Klinefelter et ulcéres de jambe: place des troubles de l'hémostase . Ann Dermatol Venereol. 1992;119: 951-957. 4. Veraart JC, Hamulyak K, Neumann HA. Leg ulcers and Klinefelter's syndrome . Arch Dermatol. 1995;131:958-959.Crossref 5. Higgins EJ, Tidman MJ, Savidge GF, et al. Platelet hyperaggregability in two patients with Klinefelter's syndrome complicated by leg ulcers . Br J Dermatol. 1989;120:322.Crossref

Dupin, Nicolas;Chosidow, Olivier;Lunel, Françoise;Fretz, Catherine;Szpirglas, Henri;Frances, Camille

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440136028

Abstract Recent reviews1,2 have focused on a hypothetical relationship between lichen planus (LP) and chronic infection with the hepatitis C virus (HCV). Indeed, several cases of concomitant LP and HCV infection have been reported.3,4 However, results of epidemiological studies5-7 are still controversial. Since oral localization is the most commonly reported form of LP related to chronic hepatitis,4,8 the aim of this study was to assess both the prevalence of HCV antibodies in a group of 102 patients with oral LP and the prevalence of oral LP in a group of 105 patients with HCV antibodies. Patients and Methods. Between March and July 1994, 102 patients with oral LP were included in this prospective study. Oral LP was diagnosed on the basis of the usual clinical features and typical histological findings.8 The control group included 306 inpatients undergoing surgery in the same institution during the same period. References 1. Pawlotsky JM, Dhumeaux D, Bagot M. Hepatitis C virus in dermatology: a review . Arch Dermatol. 1995;131:1185-1193.Crossref 2. Gumber SC, Chopra S. Hepatitis C: a multifaceted disease—review of extrahepatic manifestations . Ann Intern Med. 1995;123:615-620.Crossref 3. Mokni M, Rybojad M, Puppin D Jr, et al. Lichen planus and hepatitis C virus . J Am Acad Dermatol. 1991;24:792.Crossref 4. Jubert C, Pawlotsky JM, Pouget F, et al. Lichen planus and hepatitis C virus— related chronic active hepatitis . Arch Dermatol. 1994;130:73-76.Crossref 5. Rebora A. Hepatitis viruses and lichen planus . Arch Dermatol. 1994;130:1328-1329.Crossref 6. Gandolfo S, Carbone M, Carrozzo M, Gallo V. Oral lichen planus and hepatitis C virus (HCV) infection: is there a relationship? J Oral Pathol Med. 1994; 23:119-122.Crossref 7. Cribier B, Garnier C, Laustriat D, Heid E. Lichen planus and hepatitis C virus infection: an epidemiologic study . J Am Acad Dermatol. 1994;31:1070-1071.Crossref 8. Boyd AS, Neldner KH. Lichen planus . J Am Acad Dermatol. 1991;25:593-619.Crossref 9. Axéll T, Rundquist L. Oral lichen planus: a demographic study . Community Dent Oral Epidemiol. 1987;15:52-56.Crossref

Murata, Yozo;Kumano, Kimiko;Ueda, Takahiro;Nakamura, Toko;Tani, Masahiro

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440137029

Abstract Adelayed-type generalized skin eruption after systemic corticosteroid administration is rare. We describe a patient with systemic contact dermatitis caused by corticosteroid use. Report of a Case. A 62-year-old woman had a history of a burn treated with ointment containing hydrocortisone in 1990. No adverse effects were noted. In 1992, she was given an intra-articular injection of methylprednisolone acetate in the knee because of arthrosis. On that evening she developed erythema around the neck.In January 1994, because of sudden deafness, she was given an intravenous injection of hydrocortisone sodium phosphate, 500 mg, for 2 days, and then developed erythema on the neck, trunk, and thighs in the evening on the first day of injection. Methylprednisolone sodium succinate was substituted for the hydrocortisone. The eruption developed into a generalized rash. The methylprednisolone treatment was discontinued and the eruption resolved. She was referred to us for an evaluation of the eruption.The References 1. Coopman S, Degreef H, Dooms-Goossens A. Identification of cross-reaction patterns in allergic contact dermatitis from topical corticosteroids . Br J Dermatol. 1989;121:27-34.Crossref 2. Wilkinson SM, English JSC. Hydrocortisone sensitivity: an investigation into the nature of the allergen . Contact Dermatitis. 1991;25:178-181.Crossref 3. Menne T, Maibach HI. Systemic contact allergy reactions . Immunol Allergy Clin North Am. 1989;9:507-522. 4. Lauerma AI, Reitamo S, Maibach HI. Systemic hydrocortisone/cortisol induces allergic skin reactions in presensitized subjects . J Am Acad Dermatol. 1991;24:182-185.Crossref 5. Lauerma AI, Reitamo S. Contact allergy to corticosteroids . J Am Acad Dermatol. 1993;28:618-622.Crossref

Sperling, Leonard C.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440139030

Abstract This textbook is designed to have broad appeal and utility. Although billed as an atlas, the text is far more generous than that found in many other atlases. The entire book, index included, is only 101 pages, with lots of white space, so the entire volume can be read cover to cover in a couple of leisurely and instructive sittings. The atlas has 2 authors, one of whom (D.A.W.) is regarded by hair experts as a master of the pathologic characteristics and clinical features of hair disease. Whiting's work in the field has been that of a pioneer. He has elucidated the pathologic features of hair disease in transverse sections, organized the myriad forms of hair shaft diseases, and helped to further describe several other hair diseases. Much of the material presented by the authors cannot be found together in any single textbook, and in some cases is unavailable in References 1. Olsen E, ed. Disorders of Hair Growth: Diagnosis & Treatment . New York, NY: Health Professions Division/McGraw-Hill Book Co; 1994.

Rea, Thomas H.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440139031

Abstract Koticha's Recent Advances in Leprosy is a supplement to his previous volume, Leprosy—A Concise Text, published in 1990. The second volume is organized parallel to the previous edition, each having 11 sections and 34 chapters of identical titles and numerical sequences, covering both clinical and basic science aspects of leprosy. The current volume is based on 582 English-language references selected for inclusion by the author, in a manner somewhat similar to some yearbooks, and includes material from 1990 to 1996. The 582 references are tabulated in 41 pages. In 10 randomly selected pages of references there are 135 citations. Of these 135, 81 are abstracts (in searching MEDLINE for the years 1990 through 1996, using the command "Leprosy*.EJ," 1912 English— language references are listed). Koticha does not pretend to be a universal authority on leprosy. His selection of citations must reflect his interests and interpretations, which will surely differ from References 1. Bryceson AD, Pfaltzgraff RE. Leprosy. 3rd ed. New York, NY: Churchill Livingstone Inc; 1990. 2. Hastings RC, Opromolla DV, eds. Leprosy. 2nd ed. New York, NY: Churchill Livingstone Inc; 1994.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440143032

Abstract DURING January-April 1997, state health departments reported three fatal cases of varicella (chickenpox) to CDC. All three cases occurred in young adult women who were unvaccinated and susceptible to varicella and who were infected by exposure to unvaccinated preschool-aged children with typical cases of varicella. This report summarizes these three cases, which indicate that preventable varicella-related deaths continue to occur in the United States. In addition, the report reemphasizes the recommended strategies for preventing varicella. Case 1. On January 19, 1997, a 23— year-old woman in good health had onset of a classic varicella rash. In early January, her 2- and 5-year-old unvaccinated children had had varicella. On January 22, she had onset of shortness of breath and hemoptysis. When she was admitted to a local hospital on January 23, a chest radiograph indicated diffuse alveolar density consistent with varicella pneumonia, and treatment was initiated with oxygen and intravenous acyclovir. References 1. CDC. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP) . MMWR 1996;45(no. (RR-11) ). 2. Committee on Infectious Diseases, American Academy of Pediatrics. Recommendations for the use of live attenuated varicella vaccine . Pediatrics 1995; 95:791-6. 3. American Academy of Family Physicians. Summary of policy recommendations for periodic health examination . Kansas City, Missouri:American Academy of Family Physicians, (November) 1996. 4. Gardner P, Eickhoff T, Poland GA, et al. Adult immunizations . Ann Intern Med 1996;124:35-40.Crossref 5. Chew D, Hofmann J, O'Donnell C, Finelli L. Physician attitudes and practices regarding varicella vaccine in New Jersey [Abstract] . In: Program and abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy . Washington, DC: American Society for Microbiology, 1996:278. 6. Asano Y, Suga S, Yoshikawa T, et al. Experience and reason: twenty-year follow-up of protective immunity of the Oka strain live varicella vaccine . Pediatrics 1994;94(4 Pt (1) ):524-6. 7. Kuter BJ, Weibel RE, Guess HA, et al. Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies . Vaccine 1991;9:643-7.Crossref 8. Wallace MR, Bowler WA, Murray NB, Brodine SK, Oldfield EL III. Treatment of adult varicella with oral acyclovir: a randomized, placebo-controlled trial . Ann Intern Med 1992;117:358-63.Crossref 9. Van Loon F, Markowitx L, McQuillan G, et al. Varicella seroprevalence in US population [Abstract] . In: Program and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy . Washington, DC:American Society for Microbiology, 1993:359.

1997 Archives of Dermatology

doi: 10.1001/archderm.1997.03890440148033

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables.