Clinical and Experimental Dermatology

Brass, D.; Oliphant, T. J.; McHanwell, S.; Alexander, M.; Langtry, J. A. A.

doi: 10.1111/ced.12741pmid: 26307428

SummaryWe review the anatomy of the frontal scalp in relation to the clinical features and surgical management of frontalis‐associated lipoma. Awareness of this entity, coupled with sound regional anatomical knowledge, is essential to achieve good outcomes.

Belum, V. R.; Serna‐Tamayo, C.; Wu, S.; Lacouture, M. E.

doi: 10.1111/ced.12694pmid: 26009777

SummaryBackgroundCabozantinib is approved in the treatment of progressive, metastatic medullary thyroid cancer (MTC). It is a small molecule inhibitor, which targets multiple receptors, including vascular endothelial growth factor receptor, tyrosine kinase with Ig and epidermal growth factor homology domains‐2 and the proto‐oncogenes MET (mesenchymal–epithelial transition factor) and RET (rearranged during transfection). The drug is currently in phase I/II/III clinical trials for a number of other solid tumours and haematological malignancies. The adverse event (AE) profile is similar to that of other newer angiogenesis inhibitors. Hand–foot skin reaction (HFSR) is an important dose‐limiting dermatological adverse event of this class of drugs.AimTo ascertain the incidence and risk of HFSR in patients with cancer during treatment with cabozantinib.MethodsElectronic databases (PubMed, Web of Science) and the American Society of Clinical Oncology Meeting Library were queried from inception to July 2014. Only phase II/III studies investigating cabozantinib for the treatment of cancer were shortlisted. The incidence, relative risk (RR) and 95% CI were calculated using random‐ or fixed‐effects models, depending on the heterogeneity of the included studies.ResultsWe included 831 patients treated with cabozantinib for various solid malignancies in the analysis. The overall incidence was 35.3% (95% CI 27.9–43.6%) for all‐grade and 9.5% (95% CI 7.6–11.7%) for high‐grade HFSR. The RR of all‐grade and high‐grade HFSR with cabozantinib, compared with controls, was increased for both all‐grade (27.3; 95% CI 6.9–108.3; P < 0.001) and high‐grade (28.1; 95% CI 1.7–457; P < 0.02) HFSR, respectively.ConclusionsThe incidence and risk of developing HFSR with cabozantinib are high. Timely recognition of this dose‐limiting AE is critical to direct supportive care efforts including patient counselling, and to institute preventative and/or treatment interventions.

Shahidi‐Dadras, M.; Golfeshan, A.

doi: 10.1111/ced.12707pmid: 26213187

SummaryBackgroundThere has not been publication of any previous study about the role of secretory status or Lewis phenotypes in the mechanisms of pemphigus vulgaris (PV).AimTo evaluate the frequencies of secretory status and Lewis phenotypes in patients with PV compared with healthy controls (HCs) in order determine their roles in this autoimmune disease.MethodsIn total, 50 patients and 100 age‐ and sex‐matched HCs were selected to form the study population, and 2 mL blood were collected from each subject to identify their Lewis phenotype. In subjects with the Le(a−b−) phenotype, saliva was also collected to determine secretor status.ResultsThe frequency of the nonsecretor (NS) phenotypes Le(a+b−) and Le(a−b−) together was significantly higher in patients than in HCs: 34/50 (68%)vs. 26/100 (26%), respectively (P < 0.001). All the patients and HC subjects with the Le (a−b−) phenotype were found to be NS by haemagglutination inhibition assay of saliva samples.ConclusionBased on our results, it seems that Le/b‐negative NS individuals are more susceptible to PV.

Apalla, Z.; Calzavara‐Pinton, P.; Lallas, A.; Argenziano, G.; Kyrgidis, A.; Crotti, S.; Facchetti, F.; Monari, P.; Gualdi, G.

doi: 10.1111/ced.12713pmid: 26189480

SummaryBackgroundEpidemiological and clinical data suggest that actinic damage to the skin is an important predictor of skin carcinogenesis.AimTo investigate the association of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with sun‐damage alterations seen by histopathology.MethodIn the current prospective study, perilesional skin of SCC or BCC lesions was evaluated for presence of alterations associated with chronic photodamage. Presence of scarring, perineural/perivascular invasion, haemorrhage/haemorrhagic crust, ulceration/erosion and margin involvement were also assessed.ResultOf 6038 included lesions, 4523 (74.9%) were BCCs and 1515 (25.1%) were SCCs. Presence of actinic damage was five times more frequent in SCC than in BCC (OR = 5.29, 95% CI 4.44–6.00, P < 0.001), and diagnosis of SCC was twice as common in photo‐exposed than nonphoto‐exposed body sites (OR = 2.34, 95% CI 2.03–2.70, P < 0.001). There were twofold higher odds for actinic damage in SCC compared with Bowen disease (OR = 2.015, 95% CI 1.55–2.61, P < 0.001). Assessing the different BCC histological subtypes, we found that nodular BCC had at least twofold higher odds (OR = 2.63, 95% CI 2.09–3.32), infiltrative BCC had 48% higher odds (OR = 1.487, 95% CI 1.18–1.87) and basosquamous BCC had fourfold higher odds (OR = 4.10, 95% CI 3.01–5.57) of having actinic damage compared with superficial BCC.ConclusionsHistological verification of ultraviolet‐associated alterations in the perilesional skin in patients with NMSC in our study confirms the aetiopathogenic link between sun exposure and epithelial carcinogenesis on a histopathological basis. This correlation was stronger for SCCs than for BCCs.Conflict of interest: the authors declare that they have no conflicts of interest.

Wallis, T.; Poole, C. D.; Hoggart, B.

doi: 10.1111/ced.12723pmid: 26358843

SummaryIntroductionPachyonychia congenita (PC) is a rare skin disorder caused by an autosomal dominant mutation in one of five genes encoding keratin (K6a, K6b, K6c, K16 or K17; each defining one PC subtype). Pain is a prominent symptom, but its severity and type are poorly characterized.MethodsIn total, 35 genotyped US patients with PC consented to clinical assessment including the quality of life (QoL) questionnaire EQ‐5D‐3L, the Brief Pain Inventory (BPI) and painDETECT. Abbreviated quantitative sensory testing (QST) was also performed, and included mechanical detection threshold (MDT), mechanical pain threshold (MPT), wind‐up pain ratio (WUR) and vibration detection threshold (VDT).ResultsSignificant pain in patients with PC was confirmed, as indicated by mean BPI severity and interference of 4.2 ± 1.7 and 4.4 ± 2.2, respectively, as well as QoL impairment, as indicated by mean EQ‐5D index of 0.69 ± 0.18. PD identified neuropathic pain in 62% of patients, the remainder being nociceptive. The painDETECT score was most significantly related to EQ‐5D index (R2 = 0.26, P = 0.02). The K17 and K6a subtypes exhibited significantly worse QoL (0.584 and 0.613 respectively) than the K16 and K6b subtypes (P = 0.02). In QST analysis, abnormal pressure pain (assessed as MPT) was frequently observed, with more than half of patients with PC affected (54%), and 57% of patients with K17 also exhibiting abnormality in minimum touch threshold (assessed as MDT, P < 0.05). Very few patients were receiving analgesic therapy appropriate for neuropathic pain.ConclusionSignificant neuropathic pain was observed in PC, which warrants appropriate treatment. The health states observed in this sample are at a level that the average US citizen would forfeit one‐third of their remaining lifespan to avoid.

Sibaud, V.; Tournier, E.; Roché, H.; Del Giudice, P.; Delord, J. P.; Hubiche, T.

doi: 10.1111/ced.12675pmid: 25959005

SummaryWe report four patients developing a late form of papulopustular rash induced by epidermal growth factor receptor inhibitors. These patients presented an unusual presentation of acneiform rash, characterized by late development (several months after treatment commenced), localization to the limbs with sparing of the face, and association with severe pruritus and Staphylococcus aureus superinfection in all cases. These clinical symptoms may suggest a distinct mechanism from the early acne‐like rash frequently observed with these targeted anticancer therapies. Clinicians should be aware of this delayed adverse event, and we suggest the term ‘late acneiform toxicity of EGFR inhibitors (LATE) syndrome’ to permit better characterization of this clinical picture.

Fabbrocini, G.; Izzo, R.; Faggiano, A.; Del Prete, M.; Donnarumma, M.; Marasca, C.; Marciello, F.; Savastano, R.; Monfrecola, G.; Colao, A.

doi: 10.1111/ced.12673pmid: 26053680

SummaryAcne is a common and complex skin disease, with a very complex pathogenesis. Although in women the relationship between acne and insulin resistance is well known, in particular in women with PCOS, in males this relationship has been poorly investigated. In total, 20 subjects with an altered metabolic profile were considered for this study and randomized as follows: 10 patients were treated with metformin plus a hypocaloric diet for 6 months (group A), while 10 patients did not receive any treatment with metformin and were only followed up (group B). All patients of group A, after 6 months of metformin therapy, had a statistically significant improvement compared with patients in group B. Our study reveals the importance of diet and insulin resistance in acne pathogenesis, and underlines the possible use of metformin and diet as possible adjuvant therapy for male patients with acne.

Tan, C. H.; Shelley, C.; Harman, K. E.

doi: 10.1111/ced.12692pmid: 26053970

SummaryTetracyclines, including doxycycline, are widely used drugs that form an integral part of daily prescribing, and serious adverse reactions (SARs) are rarely reported. The frequency of hypoglycaemia complicating tetracycline treatment remains unknown, and is not a recognized complication. We describe an 80‐year‐old man with a history of insulin‐dependent diabetes who was recruited into a large research study, and subsequently experienced the unexpected SAR of hypoglycaemia following treatment with doxycycline.

McDonald, B. S.; Jones, J.; Rustin, M.

doi: 10.1111/ced.12691pmid: 26033316

SummaryBiological therapies may provide the breakthrough in treating moderate to severe atopic eczema (AE) that is unresponsive to standard therapy. Rituximab has been shown to benefit some patients in published case series, and so we treated three consecutive patients with severe AE with rituximab. Despite achieving low/absent peripheral blood CD19 + B‐cell numbers following rituximab administration, this was not associated with clinical benefit as there was no major change in pre‐ and post‐treatment Eczema Area and Severity Index (34, 64.4 and 42.2 compared with 33.2, 66 and 56.4, respectively). We would therefore recommend that that there is a compelling need for a formal, double‐blind, placebo‐controlled study to demonstrate efficacy of rituximab as a treatment of moderate to severe AE.

Fukuyama, M.; Tanese, K.; Yasuda, F.; Hayashi, Y.; Tanikawa, A.

doi: 10.1111/ced.12687pmid: 26011688

SummaryAtretic cephalocele is a small skin‐covered lesion, usually located at or near the mid‐line of the scalp. Histologically, it is composed of syncytial cells expressing neurone‐specific enolase and epithelial membrane antigen. The syncytial cells form capillary‐like structures *(pseudovascular areas) and collagenic fibrosis with densely packed collagen bundles (fibrous areas). Such findings suggest that the atretic cephalocele is a mild form of cephalocele, with its pathogenesis lying in the spectrum of neural tube closure abnormalities. However, few descriptions of abnormalities of the skin overlying and surrounding atretic cephalocele are available. We report two cases of atretic cephalocele that showed hamartomatous change in the surrounding cutaneous appendages. These findings suggest that atretic cephalocele is associated with abnormalities not only of the neural tube, but also of the surrounding skin.