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Erythema and Blistering of the Left Leg—Diagnosis

Erythema and Blistering of the Left Leg—Diagnosis Diagnosis: Fixed drug eruption (FDE). Microscopic findings and clinical course Histopathologic examination of the biopsy specimen showed vacuolar degeneration of basal cells and necrotic keratinocytes sandwiched between orthokeratotic stratum corneum and regenerating epithelium of the lower epidermis. In the dermis, edema and extravasated erythrocytes as well as a superficial and deep mixed inflammatory infiltrate with some eosinophils were observed (Figure 2). Figure 2. View LargeDownload The patient's lesions rapidly improved on treatment with a medium-potency topical corticosteroid. Two months later, patch testing with 10% co-trimoxazole in either petrolatum or aqueous base applied to the left pretibial area and to the back was performed and yielded negative results. Subsequently, trimethoprim and sulfamethoxazole were dissolved in dimethylsulfoxide at concentrations of 10% and 20% wt/vol and applied twice daily for 3 days to both left and right pretibial areas and to the back as described by Özkaya-Bayazit et al.1 Within 72 hours, the patient developed a bullous test reaction to 20% trimethoprim on the left lower leg, while the test areas treated with sulfamethoxazole or dimethylsulfoxide remained negative. In previously unaffected skin of the right lower leg and back, no reaction to trimethoprim, sulfamethoxazole, or dimethylsulfoxide was observed. Discussion Fixed drug eruption is a unique cutaneous reaction characterized by reappearance of lesions in exactly the same location each time the precipitating medication is administered. The pathogenesis of FDE remains enigmatic. One hypothesis is that the causative drug binds to epidermal proteins as a haptene and induces a lymphocyte-mediated cytotoxic reaction against keratinocytes. The site specificity of FDE may be attributable to locally residing CD8+ effector memory T cells rapidly releasing proinflammatory cytokines on drug rechallenge.2 More than 100 drugs have been described as causative agents of FDE, but sulfonamides, tetracyclines, and various nonsteroidal anti-inflammatory medications are the most common offenders. The incidence of FDE induced by a particular drug varies from country to country and from time to time, depending on local use. Co-trimoxazole represented a leading cause of FDE in several large studies from India and Turkey.3-6 Interestingly, certain drugs seem to show a preference for specific areas of the body. Tetracyclines were reported to cause FDE exclusively on the glans penis, while co-trimoxazole–induced FDE predominantly involves the lips and/or the genitalia.3,4,6 The sensitivity of topical provocation in situ in FDE is notoriously low. We succeeded in identifying trimethoprim as the causative agent in our patient only after switching to dimethylsulfoxide as a vehicle and repeated cutaneous application. This is in accordance with the data reported by Özkaya-Bayazit et al,1 who demonstrated that this protocol is greatly superior to standard patch testing in the diagnosis of co-trimoxazole–induced FDE. Interestingly, in more than 80% of cases, co-trimoxazole–induced FDE is due to its sulfamethoxazole component.1 Identification of trimethoprim as the causative agent in our patient is quite important as it suggests that she may continue using sulfonamides and a wide range of related drugs without any risk of recurrence. Also, the present case underlines the significance of obtaining a careful history and selecting appropriate testing protocols when diagnosing cutaneous drug reactions. References 1. Özkaya-Bayazit EBayazit HÖzarmagan G Topical provocation in 27 cases of cotrimoxazole-induced fixed drug eruption. Contact Dermatitis 1999;41185- 189PubMedGoogle ScholarCrossref 2. Mizukawa YYamazaki YTeraki Y et al. Direct evidence for interferon-gamma production by effector-memory-type intraepidermal T cells residing at an effector site of immunopathology in fixed drug eruption. Am J Pathol 2002;1611337- 1347PubMedGoogle ScholarCrossref 3. Thankappan TPZachariah J Drug-specific clinical pattern in fixed drug eruptions. Int J Dermatol 1991;30867- 870PubMedGoogle ScholarCrossref 4. Sharma VKDhar SGill AN Drug-related involvement of specific sites in fixed eruptions: a statistical evaluation. J Dermatol 1996;23530- 534PubMedGoogle Scholar 5. Mahboob AHaroon TS Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol 1998;37833- 838PubMedGoogle ScholarCrossref 6. Özkaya-Bayazit E Specific site involvement in fixed drug eruption. J Am Acad Dermatol 2003;491003- 1007PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Erythema and Blistering of the Left Leg—Diagnosis

Archives of Dermatology , Volume 143 (4) – Apr 1, 2007

Erythema and Blistering of the Left Leg—Diagnosis

Abstract

Diagnosis: Fixed drug eruption (FDE). Microscopic findings and clinical course Histopathologic examination of the biopsy specimen showed vacuolar degeneration of basal cells and necrotic keratinocytes sandwiched between orthokeratotic stratum corneum and regenerating epithelium of the lower epidermis. In the dermis, edema and extravasated erythrocytes as well as a superficial and deep mixed inflammatory infiltrate with some eosinophils were observed (Figure 2). Figure 2. View LargeDownload...
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Publisher
American Medical Association
Copyright
Copyright © 2007 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.143.4.536-c
Publisher site
See Article on Publisher Site

Abstract

Diagnosis: Fixed drug eruption (FDE). Microscopic findings and clinical course Histopathologic examination of the biopsy specimen showed vacuolar degeneration of basal cells and necrotic keratinocytes sandwiched between orthokeratotic stratum corneum and regenerating epithelium of the lower epidermis. In the dermis, edema and extravasated erythrocytes as well as a superficial and deep mixed inflammatory infiltrate with some eosinophils were observed (Figure 2). Figure 2. View LargeDownload The patient's lesions rapidly improved on treatment with a medium-potency topical corticosteroid. Two months later, patch testing with 10% co-trimoxazole in either petrolatum or aqueous base applied to the left pretibial area and to the back was performed and yielded negative results. Subsequently, trimethoprim and sulfamethoxazole were dissolved in dimethylsulfoxide at concentrations of 10% and 20% wt/vol and applied twice daily for 3 days to both left and right pretibial areas and to the back as described by Özkaya-Bayazit et al.1 Within 72 hours, the patient developed a bullous test reaction to 20% trimethoprim on the left lower leg, while the test areas treated with sulfamethoxazole or dimethylsulfoxide remained negative. In previously unaffected skin of the right lower leg and back, no reaction to trimethoprim, sulfamethoxazole, or dimethylsulfoxide was observed. Discussion Fixed drug eruption is a unique cutaneous reaction characterized by reappearance of lesions in exactly the same location each time the precipitating medication is administered. The pathogenesis of FDE remains enigmatic. One hypothesis is that the causative drug binds to epidermal proteins as a haptene and induces a lymphocyte-mediated cytotoxic reaction against keratinocytes. The site specificity of FDE may be attributable to locally residing CD8+ effector memory T cells rapidly releasing proinflammatory cytokines on drug rechallenge.2 More than 100 drugs have been described as causative agents of FDE, but sulfonamides, tetracyclines, and various nonsteroidal anti-inflammatory medications are the most common offenders. The incidence of FDE induced by a particular drug varies from country to country and from time to time, depending on local use. Co-trimoxazole represented a leading cause of FDE in several large studies from India and Turkey.3-6 Interestingly, certain drugs seem to show a preference for specific areas of the body. Tetracyclines were reported to cause FDE exclusively on the glans penis, while co-trimoxazole–induced FDE predominantly involves the lips and/or the genitalia.3,4,6 The sensitivity of topical provocation in situ in FDE is notoriously low. We succeeded in identifying trimethoprim as the causative agent in our patient only after switching to dimethylsulfoxide as a vehicle and repeated cutaneous application. This is in accordance with the data reported by Özkaya-Bayazit et al,1 who demonstrated that this protocol is greatly superior to standard patch testing in the diagnosis of co-trimoxazole–induced FDE. Interestingly, in more than 80% of cases, co-trimoxazole–induced FDE is due to its sulfamethoxazole component.1 Identification of trimethoprim as the causative agent in our patient is quite important as it suggests that she may continue using sulfonamides and a wide range of related drugs without any risk of recurrence. Also, the present case underlines the significance of obtaining a careful history and selecting appropriate testing protocols when diagnosing cutaneous drug reactions. References 1. Özkaya-Bayazit EBayazit HÖzarmagan G Topical provocation in 27 cases of cotrimoxazole-induced fixed drug eruption. Contact Dermatitis 1999;41185- 189PubMedGoogle ScholarCrossref 2. Mizukawa YYamazaki YTeraki Y et al. Direct evidence for interferon-gamma production by effector-memory-type intraepidermal T cells residing at an effector site of immunopathology in fixed drug eruption. Am J Pathol 2002;1611337- 1347PubMedGoogle ScholarCrossref 3. Thankappan TPZachariah J Drug-specific clinical pattern in fixed drug eruptions. Int J Dermatol 1991;30867- 870PubMedGoogle ScholarCrossref 4. Sharma VKDhar SGill AN Drug-related involvement of specific sites in fixed eruptions: a statistical evaluation. J Dermatol 1996;23530- 534PubMedGoogle Scholar 5. Mahboob AHaroon TS Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol 1998;37833- 838PubMedGoogle ScholarCrossref 6. Özkaya-Bayazit E Specific site involvement in fixed drug eruption. J Am Acad Dermatol 2003;491003- 1007PubMedGoogle ScholarCrossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Apr 1, 2007

References