Generalized Hailey-Hailey disease associated with c.2395C>T ATP2C1 gene mutation and fatal outcome.

Hailey-Hailey disease (HHD) is a rare, autosomal dominant genodermatosis caused by a mutation of the ATP2C1 gene and presenting as an erosive dermatosis, particularly in the intertriginous areas. Generalized HHD is a rare variant. We present a case of widespread, recalcitrant HHD in a middle-aged woman with a fatal outcome. No other underlying dermatosis was identified, with the possible exception of drug sensitivity to carbamazepine. Diagnosis of HHD was confirmed by histology and genetic studies which showed a c.2395C>T mutation in the ATP2C1 gene. Concurrent pemphigus was excluded. Cases of generalized HHD are extremely rare and present a challenge in diagnosis and management. Increased awareness of this severe clinical variant is needed to improve quality of care for patients with this form of HHD.

Double-Blind, Placebo-Controlled Study of Onabotulinumtoxin A for the Treatment of Hailey-Hailey Disease.

BACKGROUND: Hailey-Hailey disease (HHD) can be treated with topical steroids, antibiotics, and invasive surgical procedures. Since sweating often exacerbates HHD lesions, the use of onabotulinumtoxin A could serve as an adjunctive treatment. OBJECTIVE: The goal of this study was to evaluate the safety and efficacy of onabotulinumtoxin A for the treatment of HHD. METHODS: A double-blind, placebo-controlled single center study was conducted. Six HHD patients who successfully completed this trial in addition to 1 patient who exited early are reported and discussed. Four of these patients received an initial injection of Btx-A and 3 received the placebo initially. RESULTS: All patients except 1 who received an initial or reinjection of Btx-A decreased 2 levels on a 4-point clinical severity scale at weeks 8 or 12 after treatment. Patient 6 received an initial placebo injection and maintained clearance for 6 months, while patients 5 and 7 did not have any improvement in their target lesions after a placebo injection. All patients who received a reinjection of Btx-A at the week 4 follow-up decreased by at least 1 level on the HHD severity scale. CONCLUSION: Btx-A is a safe treatment that is effective for most cases of HHD. The most severe cases of HHD may not respond to Btx-A as sole treatment. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.6857 Citation: Saal R, Oldfield C, Bota J, et al. Double-blind, placebo-controlled study of Onabotulinumtoxin A for the treatment of Hailey-Hailey disease. J Drugs Dermatol. 2023;22(4):339-343. doi:10.36849/JDD.6857.

Grouped follicular secondary syphilis: Case report and review of literature.

Secondary syphilis typically presents with macular, maculopapular or papular lesions, sometimes with systemic symptoms; however, there are some less common cutaneous presentations which can result in several differential diagnoses. We report the case of a 25-year-old man with the recent onset of a symmetric eruption of grouped follicular papules, for which syphilis was not originally considered. Histopathology revealed non-caseating granulomas with a lichenoid infiltrate. Subsequent spirochete immunostaining was positive, and further physical examination revealed moth-eaten alopecia, confirming the diagnosis of secondary syphilis.

Painful, Tender, Localized, Idiopathic Livedo Reticularis.

Livedo reticularis (LR) is a unique cutaneous condition characterized by a reddish-blue to purple, net-like cyanosis of the skin, often associated with disturbances in cutaneous blood flow. This case report discusses a 30-year-old woman with a history of Hashimoto thyroiditis, vitamin D deficiency, migraines, and goiter who presents with painful, localized LR on her right flank. Despite her extensive medical history, there were no significant findings in her laboratory and imaging studies, including a normal epidermis in skin biopsies. The LR in this case is distinguished by its persistence and the presence of pain, a symptom not commonly associated with LR. Various treatments, including 5% lidocaine ointment, oral analgesics, and gabapentin, were considered, but her symptoms remained stable over 13 months. This case exemplifies the complexity of LR, particularly when presenting with atypical symptoms like pain. It highlights the need for further research into the pathophysiology and treatment of LR, especially in cases deviating from the typical symptomatology, and suggests the potential value of a multi-disciplinary approach to management.

Late subsequent Merkel cell carcinoma after 21 years of the first primary diagnosis: When to de-escalate surveillance?

Key Clinical Message: Merkel cell carcinoma (MCC) presents challenges in surveillance due to varied recurrence rates and uncertain follow-up protocols, especially in late recurrent cases. These cases need personalized monitoring strategies beyond traditional timelines, such as clinical and molecular factors, in order to optimize patient outcomes. Abstract: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with neuroendocrine differentiation with a propensity for recurrence following initial treatment. Surveillance strategies for MCC patients lack specificity, and the duration of surveillance remains uncertain, posing challenges in identifying appropriate follow-up intervals. Therefore, we present a 94-year-old woman, with history of stage IA MCC in her left nasal wall 21 years prior, that presented with a dome-shaped eroded nodule on her left fifth finger. Biopsy showed characteristic MCC features with positive immunohistochemistry for CD56, synaptophysin, and CK20 (perinuclear dotting). The patient opted against further imaging or lymph node biopsy and underwent Mohs micrographic surgery. To date, there has not been any evidence of recurrence at previous sites or development of new primary lesions. This case underscores the need for ongoing surveillance despite long disease-free intervals. It also stands out as the case demonstrating the longest latency/recurrence-free interval following the initial diagnosis of MCC in the literature. While most recurrences occur within the first few years post-diagnosis, our case highlights the exceptional nature of late recurrences and prompts reevaluation of surveillance protocols. Current guidelines recommend surveillance for up to 3 years post-treatment, but factors, such as patient demographics and tumor characteristics, may warrant extended monitoring periods. Emerging biomarkers, such as Merkel cell polyomavirus status and circulating tumor DNA, show promise in predicting and monitoring recurrences, but their utility in late recurrence detection requires further investigation.

Discrepancies in Non-Mohs Micrographic Surgery for Non-melanoma Skin Cancer Between Lighter-Skinned and Darker-Skinned Patients.

BACKGROUND: Non-melanoma skin cancer (NMSC) is highly prevalent in the United States, with darker-skinned patients (DSP) exhibiting lower incidence but increased morbidity and mortality. The purpose of this study is to elucidate NMSC disparities between DSP (Fitzpatrick skin phototype IV or more) and lighter-skinned patients (LSP, Fitzpatrick skin phototype III or less), focusing on surgical features of non-Mohs micrographic surgery-treated NMSC. METHODS: This retrospective cohort study included LSP and DSP diagnosed with either basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in an academic dermatology setting. Variables collected included age, gender, type of NMSC, location, staging, time-to-diagnosis (TTD), pre-operative lesion size, and post-operative defect size. Categorical variables were reported as counts and percentages, while the association between categorical variables was assessed using a two-tailed Fisher's test. A paired t-test was used to determine the association between continuous variables. P-values <0.05 were considered statistically significant. RESULTS: A total of 27 patients with NMSC were identified, of which 9 (33.3%) were DSP. Patients of darker skin were predominantly female (n=7; 77.8%), while no gender predilection was found in LSP (n=9; 50.0% female; p=0.23). Time-to-diagnosis was significantly longer in DSP than in LSP (61.3 weeks vs 25.1 weeks, respectively; p = 0.02). Despite this, there was no statistical difference in terms of staging, pre-operative lesion size (11.89 mm in DSP vs 10.76 mm in LSP, p=0.75), and post-operative defect size (45.56 ± 29.21 mm in DSP vs 31.22 ± 19.60 mm in LSP; p=0.33). CONCLUSIONS: Darker-skinned patients had a longer TTD without staging differences. Our study confirms the need for reducing TTDs for NMSC in DSP. Action initiatives include continued educational efforts to increase awareness of NMSC risk in DSP and more rigorous routine skin cancer screening.

A double-blind, randomized, placebo-controlled trial of adalimumab in the treatment of cutaneous sarcoidosis.

BACKGROUND: Many medications, including tumor necrosis factor antagonists, have been anecdotally reported to be effective in treating cutaneous sarcoidosis, but controlled study is lacking. OBJECTIVE: We sought to determine if adalimumab is a safe and effective treatment for cutaneous sarcoidosis. METHODS: Adalimumab or placebo was administered to 10 and 6 patients, respectively, in double-blind, randomized fashion for 12 weeks, followed by open-label treatment for an additional 12 weeks, followed by 8 weeks of no treatment. Assessments were made of cutaneous lesions, quality-of-life issues, laboratory findings, pulmonary function, and radiographic findings. RESULTS: At the end of the 12-week, double-blind phase, there was improvement in a number of cutaneous findings in the adalimumab-treated patients (group 1) relative to placebo recipients (group 2), most notably in target lesion area (P = .0203). At the end of the additional 12-week open-label phase, significant improvement relative to baseline was found for target lesion area (P = .0063), target lesion volume (P = .0225), and Dermatology Life Quality Index score (P = .0034). No significant changes were seen in pulmonary function tests, radiographic findings, or laboratory studies. After 8 weeks off treatment, there was some loss of this improvement. LIMITATIONS: Standardized, validated measures for cutaneous sarcoidosis are lacking. There may be observer bias in the open-label portion of this study. The small size of this study makes it difficult to generalize results. CONCLUSIONS: Adalimumab, at the dose and duration of treatment used in this study, is likely to be an effective and relatively safe suppressive treatment for cutaneous sarcoidosis.

Changing age distribution of melanoma patients: a 22-year, single-site perspective.

OBJECTIVES: To investigate possible changes in the demographics of patients with melanoma during a period of 22 years in one dermatopathology practice. METHODS: We performed a retrospective review of 1835 cases of in situ and invasive melanomas histologically diagnosed between 1989 and 2010 in a private dermatopathology laboratory in Norfolk, Virginia. The age and sex of patients with in situ and invasive melanomas were recorded and compared with similar data for patients from whom any histopathologic specimen was received during the same interval. These data were then compared with those in the national Surveillance, Epidemiology, and End Results (SEER) registry between 1989 and 2009. RESULTS: The number of melanomas diagnosed in the laboratory increased during the 22 study years, but the proportion of submitted specimens diagnosed as melanoma remained somewhat stable. Patient ages ranged from the teens to the ninth decade of life. The proportion of melanomas in the in situ stage gradually increased. Mean patient age rose from 52.4 years in 1989 to 60.7 years in 2010. Men and women aged 60 years and older made up an increasing proportion of melanoma cases. There also was a relative increase in the proportion of women in the 40- to 50-year-old age group and a slight increase among those aged 20 to 30 years, particularly for invasive lesions. In general, the trends were similar for in situ and invasive melanomas. Our data were consistent with the SEER data in showing a trend for decreasing proportion of melanomas in younger individuals, with a corresponding increase in the middle-age and older adult populations. Some differences between the two datasets emerged for men aged 70 to 80, women aged 60 to 70, and all patients aged 70 to 80. CONCLUSIONS: An increasing proportion of melanomas were diagnosed in older individuals. There also was a relative increase in women aged 40 to 50 years and a lesser increase in those aged 20 to 30 years. Our findings were consistent with the national trends observed in the SEER dataset.

Nonbullous neutrophilic lupus erythematosus: a newly recognized variant of cutaneous lupus erythematosus.

BACKGROUND: Neutrophils in the setting of systemic lupus erythematosus (SLE) are commonly associated with bullous disease. Rare cases of nonbullous neutrophilic lesions have been reported in patients with SLE. OBJECTIVE: This study used clinical and histologic findings of 4 patients to further define the newly emerging entity of nonbullous neutrophilic lupus erythematosus (LE). METHODS: We reviewed the clinical and pathological findings of 4 patients with known SLE who developed urticarial papules, plaques, subcutaneous nodules, or a combination of these. RESULTS: All patients were women with established SLE. Histopathological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, and variable vacuolar alteration along the dermoepidermal junction. Direct immunofluorescence study results in two patients were positive for C3, IgG, and IgM along the basement membrane zone. One patient also presented with neutrophil-rich lupus panniculitis. All clinical lesions resolved with immunomodulating/immunosuppressive agents. LIMITATIONS: This study was limited by the small number of cases. CONCLUSIONS: Nonbullous neutrophilic LE is an important entity to consider in the differential diagnosis of neutrophil-mediated eruptions. In addition, the histologic finding of neutrophils in the setting of lupus should alert one to the possibility of systemic disease.

Unilateral Distribution of Lichen Planus Pigmentosus-Inversus Unresponsive to Clobetasol and Hydroquinone.

Lichen planus pigmentosus-inversus (LPP-inversus) is a rare, pigmented variant of lichen planus of unknown etiology. This skin condition typically affects the intertriginous and flexural regions of the body bilaterally. We report an unusual case presentation with unilateral distribution of LPP-inversus in a woman originally from Nepal. The lesions developed rapidly over a three-month period and were recalcitrant to therapy with topical clobetasol and hydroquinone.

Acquired acrodermatitis enteropathica secondary to alcoholism.

Acrodermatitis enteropathica is a zinc deficiency disorder characterized by well-demarcated, erythematous, eczematous plaques in a periorificial and acral distribution. Hereditary and acquired forms have been described. We report a case of acquired acrodermatitis enteropathica secondary to alcoholism. Treatment of the underlying disorder and zinc replacement therapy resulted in rapid resolution of the condition.

Laptop computer-induced erythema ab igne: a case report.

Erythema ab igne is a condition characterized by reticulated telangiectasia and hyperpigmentation caused by repeated long-term exposure to infrared radiation insufficient to produce a burn. We report a case of laptop computer-induced erythema ab igne.