Suprabasal acantholytic dermatologic toxicities associated checkpoint inhibitor therapy: A spectrum of immune reactions from paraneoplastic pemphigus-like to Grover-like lesions.

Checkpoint inhibitors (CPIs) restore the function of effector immunocytes to target and destroy cancer cells. Immune-related adverse events (irAEs) are a consequence of immune reactivation, with unpredictable inflammatory response, loss of self-tolerance, and development of autoimmunity. Adverse events from CPIs that present as dermatologic toxicities have diverse clinical and histopathologic features. CPI-associated dermatologic toxicities may exhibit histopathologic features of lichenoid dermatitis, bullous pemphigoid, and granulomatous/sarcoid-like reactions. Suprabasal acantholytic dermatologic toxicities associated with CPIs are particularly rare but represent an emerging histopathologic pattern and include lichenoid dermatitis with suprabasal acantholysis/vesicle formation to Grover disease (transient acantholytic dermatosis). Here, we report two patients who developed suprabasal acantholytic dermatologic toxicities during CPI therapy. One patient exhibited a CPI-associated autoimmune blistering disease with paraneoplastic pemphigus (PNP)-like features restricted to histopathology and immunofluorescence, while the other patient had Grover-like lesions. A review of the literature revealed a spectrum of suprabasal acantholytic dermatologic toxicities associated CPIs that may present as lichenoid dermatitis with acantholysis/vesicle formation, Grover-like eruptions, and lesions with PNP-like features restricted to histopathology and immunofluorescence. It is important for clinicians and pathologists to recognize the types of dermatologic toxicities associated with CPIs to direct appropriate therapeutic strategies.

Tinea Capitis Masquerading as Basal Cell Carcinoma.

A 52-year-old white man with alcoholic cirrhosis presented to the Mohs surgery clinic with a 1-month history of tender "bumps" located diffusely on his scalp. Two biopsies performed at an outside institution were read as "basal cell carcinoma" and "actinic keratosis." The patient was scheduled for a large excision of the scalp for presumed multiple nodules of basal cell carcinoma and desired a second opinion from our Mohs surgery clinic.

No pain no gain: tender nodules in a competitive bodybuilder.

The subculture of bodybuilding is rife with people willing to do whatever is necessary to achieve the perfect physique. One particularly concerning behavior is the injection of site-enhancing-oils (SEO) into lagging muscle groups to achieve instant size and symmetry. The typical SEO is a combination of lidocaine, alcohol, and oil; it is rarely, if ever, administered by a qualified professional. As a result, there are a variety of potential complications that can manifest in the skin and other organ systems. In our case, a 41-year-old former competitive bodybuilder was referred to our clinic for excision of a subcutaneous nodule. The initial histopathology was concerning for lymphoma, but a more thorough history and review of systems were completely negative. The patient underwent a negative systemic lymphoma workup and it was not until we discussed the prospects of radiation and other forms of treatment that he revealed a history of SEO use, as well as other identical nodules on his body. Subsequent excisions revealed a more classic sclerosing lipogranuloma-type reaction pattern. Owing to the taboo nature of SEOs, most patients are reluctant to provide this vital piece of historical information, highlighting the importance of patient rapport and clinical-pathologic correlation in our specialty.

Adult-onset papular purpuric gloves and socks syndrome.

Papular purpuric gloves and socks syndrome (PPGSS) is a self-limited exanthem that presents as painful or pruritic edema, erythema, petechiae, and purpura of the palms and soles with occasional extension to the dorsal hands and feet. The majority of PPGSS cases reported in the literature are associated with parvovirus B19 and occur in children and young adults. In a recent literature search, there were 11 PPGSS cases in adults with none reporting Epstein-Barr virus (EBV) as a viral etiology. However, there have been PPGSS cases related to EBV in children. We report the case of a 72-year-old man with PPGSS associated with Epstein-Barr virus. This case report serves as a reminder that PPGSS can present not only in the setting of pediatric and young adult parvovirus B19 infection, but also in immunocompetent adults with other viral infections.

Deep Granuloma Annulare Mimicking Inflamed Cysts in a Teenager.

We describe deep granuloma annulare (DGA) of the forehead mimicking inflamed cysts. Reactive inflammation and sterile purulent drainage may be an underrecognized feature of DGA.

A case of leukocytoclastic vasculitis caused by novel anticoagulant rivaroxaban.

Cutaneous leukocytoclastic vasculitis (LCV) is type of small vessel vasculitis that commonly presents as palpable purpura involving the lower extremities and buttocks. Approximately half of cases are idiopathic, but the disease may be triggered by infection, drug reaction, inflammatory disease, or other causes. We report a case of leukocytoclastic vasculitis secondary to the novel anticoagulant rivaroxaban (Xarelto®).

Generalized eruptive histiocytosis associated with a novel fusion in LMNA-NTRK1.

Non-Langerhans cell histiocytosis (NLCH) is a histiocyte disorder comprised of dermal dendritic histiocytes with a characteristic staining pattern. Erdheim-Chester disease (ECD) is a subset of NLCH in which patients experience bone pain with corresponding changes on imaging. In addition, these patients show other evidence of systemic involvement, which can also be identified with imaging. This disease can occasionally present with cutaneous findings. We present a case of generalized eruptive histiocytosis (GEH), misdiagnosed as ECD, found to have an NTRK1 gene rearrangement. This is the first report of an NTRK1 kinase fusion with NLCH. The implication is unclear and further studies are warranted.

A verrucous presentation of mycosis fungoides.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma and can have a variety of clinical and histological manifestations, including erythrodermic, pustular, bullous, hypo/hyperpigmented, and verrucous forms. We describe a case of a 59-year-old woman who presented with verrucous hyperkeratotic plaques on her distal fingertips, dorsal feet, and areolae that were subsequently biopsied and shown to be mycosis fungoides. This case highlights one of the many atypical manifestations of MF and underscores the need to have a high clinical suspicion for the disease.

Primary mucocutaneous histoplasmosis in an immunocompetent patient.

We report a case of primary mucocutaneous histoplasmosis in an immunocompetent individual. The patient, a 61-year-old woman, presented with a non-healing ulcer on the lateral border of her tongue. Excisional biopsy of the lesion was consistent with histoplasmosis and no evidence of pulmonary or disseminated infection was found. Although mucocutaneous infection has been well-described as a manifestation of disseminated disease, especially in immunocompromised individuals, oral infections in immunocompetent patients are rare.

Hydrochlorothiazide and cutaneous T cell lymphoma: prospective analysis and case series.

BACKGROUND: Mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are the most common cutaneous T cell lymphomas (CTCL), but their etiology remains unknown. After patients were observed with hydrochlorothiazide (HCTZ)-associated CTCL, HCTZ was examined as a putative chronic antigen in a cohort of prospectively staged patients. METHODS: Demographic and drug exposure data was examined from 1443 confirmed MF and SS patients. Hypertensive CTCL patients were divided into HCTZ users or nonusers for statistical analysis by chi-square and t tests. Causality in a case series was rated by the Naranjo Adverse Drug Reaction Probability Scale. RESULTS: A total of 815 of 1443 MF and SS patients (56.5%) were hypertensive; 205 (25.2%) were taking HCTZ at initial staging. Comparing stage of patients who were using or not using HCTZ, the most significant difference was between stage I and stage IV (odds ratio of 0.45; 95% confidence interval of 0.25-0.78, P = .003), demonstrating reduced likelihood of being stage IV in patients who were on HCTZ. Seventy-seven percent of the MF patients on HCTZ were stage I. A total of 125 patients of 196 (63.8%) started HCTZ prior to developing CTCL lesions, and 35 of 121 (28.0%) started within 1 year of first skin rash. Thirty-six of 125 patients (28.8%) experienced complete or partial remissions after discontinuing HCTZ. A monoclonal T cell receptor rearrangement was detected more frequently in the hypertensive stage I patients not taking HCTZ as compared with those who were (55.3% vs 69.1%, P = .032). Three patients were rechallenged and developed MF lesions that resolved or improved with discontinuation. CONCLUSIONS: HCTZ is commonly prescribed and may be a putative antigen in a small subset of early MF patients. Careful drug histories and a trial off medication are warranted.

Digital photography for the dermatologist.

Dermatology is a specialty reliant on presenting detailed and accurate visual observations. Digital photography is a highly prevalent and accessible technology that can be easily incorporated into a dermatology practice to facilitate documentation and communication of clinical findings. Dermatologists will benefit from being comfortable with digital photography and techniques to improve their photography skills. This review presents the fundamentals of photography and techniques helpful in capturing an adequate image. We explore the application of photography in the setting of microscopy, dermatopathology, dermatoscopy, and Wood's lamp. Lastly, new imaging technologies, such as multispectral and infrared imaging, are discussed.

Detection of coxsackievirus A6 in formalin-fixed, paraffin-embedded skin biopsy specimens using immunohistochemistry and real-time reverse-transcriptase PCR.

Background: Hand, foot, and mouth disease (HFMD), classically a childhood viral infection, has an atypical and severe clinical presentation in adults. Coxsackievirus A6 is a leading cause of atypical HFMD, but current diagnostic methods utilizing formalin-fixed, paraffin-embedded skin biopsy specimens often lack sensitivity and specificity. Methods: Formalin-fixed, paraffin-embedded skin biopsies from seven case patients with clinical and histopathological suspicion of atypical HFMD were evaluated by coxsackievirus A6 (CVA6) immunohistochemistry, enterovirus-specific conventional reverse transcriptase-PCR with subsequent Sanger sequencing targeting the 5'UTR, and CVA6-specific real-time PCR targeting the VP1 gene. Results: The CVA6-specific antibody demonstrated appropriate antigen distribution and staining intensity in keratinocytes in all cases. Conventional RT-PCR and sequencing also detected the presence of enterovirus, and CVA6-specific real-time RT-PCR analysis identified CVA6. Conclusion: Applying these immunohistochemistry and molecular techniques to formalin-fixed, paraffin-embedded tissues, CVA6 was determined to be the causative infectious agent in seven cases of atypical hand, foot, and mouth disease.