Novel hyperpigmentation pathophysiology following a prolonged course of imipramine therapy.

Imipramine is a tricyclic antidepressant typically reserved for patients with treatment-resistant mood disorders. A rare side effect of long-term use of imipramine is a slowly progressive melanin-associated, slate gray-blue hyperpigmentation of the skin in a photo-distributed pattern. We report a case of imipramine-induced hyperpigmentation developing 50 years after initiating imipramine therapy, whose lesions were essentially devoid of melanin on histopathological exam. This differs from all other reported cases of imipramine-induced hyperpigmentation in two notable respects. First, the time between initiating imipramine therapy and the onset of pigmentation changes was nearly 30 years longer than prior case reports. Second, the lack of melanin in our samples suggests a divergence from the hypothesized melanin-imipramine complex mechanism of hyperpigmentation. Instead, we propose a novel pathogenesis of imipramine-induced hyperpigmentation that is unrelated to melanin.

Myelodysplasia cutis masquerading as granulomatous dermatitis.

Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic neoplasms resulting from mutations in stem cells. They carry a risk of transformation to acute myeloid leukemia. Cutaneous manifestations of MDS, including myelodysplasia cutis or infiltration by MDS tumor cells, are rare, but significantly associated with increased risk of progression to high-grade myeloid tumors. The clinical and histopathologic differential diagnosis for myelodysplasia cutis includes interstitial granulomatous dermatitis (IGD), a reactive granulomatous dermatitis (RGD) associated with systemic diseases including rheumatologic diseases, and hematologic malignancy like MDS. We report a patient with MDS who presented with myelodysplasia cutis masquerading as IGD both in a clinical and histopathological manner.

Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part II: Methotrexate, alkylating agents, biologics, and small molecule inhibitors.

In solid organ transplant recipients, skin cancer risk associated with posttransplant immunosuppression has been well-described, and screening practices generally reflect these risks. In addition to agents used posttransplant, other classes of immunosuppressants also have the potential to raise the risk of nonmelanoma skin cancer (NMSC) or melanoma. In the present manuscript, the evidence for melanoma and NMSC risk associated with methotrexate, cyclophosphamide, biologic cytokine inhibitors including TNF (tumor necrosis factor)-alpha and interleukin inhibitors, costimulation blockers such as abatacept, integrin inhibitors such as natalizumab, targeted B-cell, and T-cell inhibitors including CD20 (cluster of differentiate 20), CD52, and BTK (Bruton's tyrosine kinase) inhibitors, and JAK (Janus kinase) inhibitors is reviewed. Based on the available data, we recommend regular skin cancer screening for select nontransplant patients receiving immunosuppressive regimens that are shown to raise the risk of NMSC or melanoma. We also offer suggestions for conscientious use of these therapies in high-risk patients. Finally, a comprehensive summary of the relative risk associated with each immunosuppressant class and associated recommendations is presented.

Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part I: Calcineurin inhibitors, thiopurines, IMDH inhibitors, mTOR inhibitors, and corticosteroids.

Immunosuppression is a well-documented risk factor for skin cancer, as exemplified by the 65- to 250-fold higher squamous cell carcinoma risk, 10-fold higher basal cell carcinoma risk, and 0 to 8-fold higher melanoma risk in solid organ transplant recipients (SOTRs) receiving potent, prolonged courses of immunosuppressive therapies. Numerous immune system components have been shown to either suppress or promote tumor growth, and immunosuppressive drugs may have additional effects on proliferative pathways independent of the immune system. Thus, evaluation of the specific regimen by the dermatologist is key for assessing skin cancer risk in each patient. In the present manuscript, the immune-mediated mechanisms of skin cancer development and regression are first reviewed. Next, a synthesis of the evidence shows the differing effects of immunosuppressive agents commonly used in SOTRs on melanoma and nonmelanoma skin cancer risk. These include systemic calcineurin inhibitors, thiopurines, IMDH (inosine monophosphate dehydrogenase) inhibitors, mTOR (mammalian target of rapamycin) inhibitors, and systemic corticosteroids. Finally, recommendations for skin cancer screening in SOTRs are discussed. We further offer recommendations for select nontransplant patients who may benefit from routine skin cancer screening due to risks associated with specific immunosuppressant exposure, and we propose evidence-based strategies for minimizing high-risk immunosuppressant use in clinical practice.

Crowdsourcing Medical Costs in Dermatology: Cross-sectional Study Analyzing Dermatologic GoFundMe Campaigns.

BACKGROUND: Crowdfunding for medical costs is becoming increasingly popular. Few previous studies have described the fundraising characteristics and qualities associated with success. OBJECTIVE: This study aimed to characterize and investigate the qualities associated with successful dermatological fundraisers. METHODS: This cross-sectional study of dermatological GoFundMe campaigns collected data, including demographic variables, thematic variables using an inductive qualitative method, and quantitative information. Linear regression examined the qualities associated with success, which are defined based on funds raised when controlling for campaign goals. Logistic regression was used to examine qualities associated with extremely successful campaigns, defined as those raising >1.5 times the IQR. Statistical significance was set at P<.05. RESULTS: A total of 2008 publicly available campaigns at the time of data collection were evaluated. Nonmodifiable factors associated with greater success included male gender, age 20-40 years, and White race. Modifiable factors associated with success included more updates posted to the campaign page, non-self-identity of the campaign creator, mention of a chronic condition, and smiling in campaign profile photographs. CONCLUSIONS: Understanding the modifiable factors of medical crowdfunding may inform future campaigns, and nonmodifiable factors may have policy implications for improving health care equity and financing. Crowdfunding for medical disease treatment may have potential implications for medical privacy and exacerbation of existing health care disparities. This study was limited to publicly available GoFundMe campaigns. Potential limitations for this study include intercoder variability, misclassification bias because of the data abstraction process, and prioritization of campaigns based on the proprietary GoFundMe algorithm.

An unusual case of T-cell prolymphocytic leukemia mimicking a cutaneous vasculitis.

T-cell prolymphocytic leukemia (T-PLL) is an aggressive post-thymic T-cell malignancy, which accounts for 2% of mature lymphocytic leukemias in adults. Though typically presenting with a brief history of B symptoms, hepatosplenomegaly, and marked lymphocytosis, erythematous or nodular skin rashes involving the trunk or limbs may be seen in 25% to 30% of patients, as well as a purpuric rash in a periorbital distribution. Cutaneous involvement typically presents in the context of patients with an established history of T-PLL, but it can less frequently present as an initial symptom heralding the diagnosis. An unusual case of T-PLL is described, presenting initially as palmoplantar ulcerated nodules with an initial biopsy suggestive of perniosis, followed by rapid progression of dark violaceous and bright red papules throughout the body after initiation of obinutuzumab. The diagnosis of T-PLL was subsequently fully supported by the clinical, laboratory, cytologic, and immunophenotypic findings. This case highlights the importance of a multidisciplinary team approach to address such rare and atypical presentations.

Methotrexate Monitoring in Dermatology- A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: There are currently no evidence-based recommendations to guide lab monitoring in the first 90 days of methotrexate treatment. The purpose of this study was to determine whether certain monitoring practices or baseline patient characteristics were associated with increased risk of developing clinically meaningful lab abnormalities during the course of methotrexate treatment. PATIENTS AND METHODS: This retrospective cohort study analyzed 243 dermatologically managed patients taking methotrexate at the University of Virginia Health System. Odds ratios were used to analyze the risk of these patients developing lab abnormalities that result in a change in clinical management, referred to as clinically relevant events. Chi-square analysis was used to determine the optimal timing of methotrexate lab monitoring. RESULTS: A diagnosis of congestive heart failure (P=0.03), chronic kidney disease (P=0.03), and an initial low platelet count (P=0.008) increased the odds of developing a clinically relevant event at some point during methotrexate therapy. In the first 15 days following methotrexate initiation, only 1/114 (0.9%) lab draws resulted in discontinuation of the medicine, 1/114 (0.9%) resulted in maintenance of a stable dose, and 2/114 (1.8%) resulted in repeat laboratory testing. CONCLUSION: In the absence of concerning baseline patient characteristics, dermatologists may consider postponing initial lab monitoring until 15 days post methotrexate initiation.J Drugs Dermatol. 2021;20(3):320-325. doi:10.36849/JDD.5790.

Pemphigus erythematosus: A case series from a tertiary academic center and literature review.

BACKGROUND: Pemphigus erythematosus (PE) is a rare autoimmune skin condition with clinical, histopathological, and serological features that show overlap between lupus erythematosus and pemphigus foliaceus. It typically presents with erythematous, scaly plaques and has a female predominance. METHODS: After Institutional Review Board (IRB) approval, we searched the internal pathology database for "pemphigus erythematosus" in the diagnostic line between 1 January 2000 and 30 July 2020. A comprehensive chart review was performed to collect patient demographics, clinical presentation, and treatment course. We performed a review of the literature and clinical, histopathological, and serological features were collected for comparison to our case series. RESULTS: Five patients in the case series and 87 patients in the literature were diagnosed with PE. Clinical, histopathological, and serological features were consistent with what has been reported in the literature, although our cohort demonstrated a younger age at presentation, along with a higher proportion (80%) of Black patients. Of the 25 patients in the literature whose race was reported, only five patients (20%) were reported to be Black. CONCLUSION: This is the first case series of PE that has shown an increased prevalence among middle-aged Black patients. No specific trend in regards to race was seen in the review of the literature.

"What Do You Mean It's Not Cancer?" A Review of Autoimmune and Systemic Inflammatory Diseases Involving the Breast.

Autoimmune and systemic inflammatory diseases represent a heterogeneous group of immune-mediated conditions with a wide range of clinical presentations and various affected organs. Autoimmune diseases can present in the breast as localized disease or as part of systemic involvement. Although breast involvement is uncommon, the spectrum of imaging findings can include breast masses, axillary adenopathy, calcifications, and skin changes, the appearance of which can mimic breast cancer. Common etiologies include diabetic mastopathy, systemic lupus erythematosus, scleroderma, rheumatoid arthritis, idiopathic granulomatous mastitis, sarcoidosis, and Immunoglobulin-G4 related mastopathy. This educational review will present multimodality imaging findings of breast manifestations of systemic inflammatory and autoimmune diseases and coexisting complications. It will also review how these disorders may affect breast cancer risk and breast cancer treatment options, including radiation therapy.

Larval tick infestation causing an eruption of pruritic papules and pustules.

Ticks are well-documented human parasites and vectors of infectious disease. The larval ("seed") stage is 1 of 3 motile life stages, and larval ticks have been known to attack in droves, causing diffuse pruritic erythematous papules and pustules. In the absence of close examination, larval tick infestation can easily be missed in the wide differential for this clinical presentation. We present 2 cases of larval tick infestation occurring during the summer within the same month at a single institution. Our purpose is to encourage physicians to include larval tick infestation when generating a differential diagnosis for diffuse pruritic erythematous papules and pustules.

IgG4-Related Skin Disease Presenting as a Pseudolymphoma in a White Adolescent Girl.

Immunoglobulin gamma (Ig) type 4-related disease (IgG4-RD) is a chronic immunologic systemic disorder that has gained worldwide recognition in the past decade. This entity can affect almost every organ system, and its characteristic lesions have been found in a variety of organs such as lacrimal and salivary glands, pancreas, liver, bile ducts, lungs, kidneys, retroperitoneum, breast, aorta, thyroid, and prostate. This case reports a very rare case of IgG4-RD presenting with a cutaneous lesion in a young female patient mimicking a lymphoproliferative disorder. IgG4-RD affecting the skin is a rare entity and has mostly been reported in Japanese men of middle to older age. IgG4-RD with cutaneous involvement should be in the differential of non-neoplastic, lymphomas, autoimmune, and infectious disorders of the skin.

Darier Nests or Pautrier microabscesses: highlighting the confusion of a decade.

Lucien Marie Pautrier was a skilled dermatologist whose work led to the creation of numerous manuscripts within the field of dermatology. His name, though, most often lends itself to a histopathological finding that was not his own discovery. For years, the origin of the term "pautrier microabscess" was thought to be the result of a misattribution by Louis H. Winer at the 66th annual meeting of the American Dermatological Association in 1946. However, a recently reported citing of the term in a 1932 article has led to speculation that the term could, in fact, have been first coined at a meeting of the New York Society of Dermatology in 1927.

Necrobiosis lipoidica associated with sarcoidosis.

We report the case of a 40-year-old African-American female with biopsy-proven pulmonary sarcoidosis who developed atrophic plaques on her shins, trunk, and scalp that were clinically and histologically consistent with necrobiosis lipoidica (NL). The lesions appeared 3 years after her diagnosis of sarcoidosis, and progressed despite chronic prednisone. Sarcoidosis and NL are granulomatous skin disorders reported to coexist in the same patient only 10 times in the literature. Including the current case, patients have been exclusively females around middle age, and have greater tendencies to develop typical cutaneous sarcoidosis. The incidence of diabetes is rare in this group. Like typical NL, NL associated with sarcoidosis tends to ulcerate, and is difficult to treat. Interestingly, there are six similar cases reported in the literature of patients with sarcoidosis who developed lesions clinically and behaviorally consistent with NL, but received a final histological diagnosis of sarcoidosis. These cases share very similar demographics and clinical features with cases of true NL associated with sarcoidosis, and often have more ambiguous histology containing features of both cutaneous sarcoidosis and NL. Comparing the two sets of cases raises the possibility of a final common disease pathway shared by these two granulomatous skin disorders.

Treatment of subcutaneous sarcoidosis with hydroxychloroquine: report of 2 cases.

Although the therapeutic benefit of oral antimalarials in various types of sarcoidosis is well described, their reported use specifically in subcutaneous sarcoidosis (Darier-Roussy type sarcoidosis) is limited. We describe the cases of two patients with subcutaneous sarcoidosis treated with hydroxychloroquine, suggesting that it may represent an alternative first-line treatment for patients in whom steroid-sparing therapy is desired.