Ruth Ann Vleugels

Calciphylaxis: A systematic review of existing and emerging therapies

Calciphylaxis, also known as calcific uremic arteriolopathy, is a cutaneous ischemic small vessel vasculopathy seen in 1 to 4% of patients with chronic kidney disease on hemodialysis. It is associated with extreme pain and a 60 to 80% mortality rate in the setting of few and frequently ineffective therapeutic options, although this may be changing based on reports of success with newer therapies.

Drug-Associated Dermatomyositis Following Ipilimumab Therapy: A Novel Immune-Mediated Adverse Event Associated With Cytotoxic T-Lymphocyte Antigen 4 Blockade

IMPORTANCE Ipilimumab, a human monoclonal antibody targeted against cytotoxic T-lymphocyte antigen 4, has shown promise in the treatment of metastatic melanoma. However, given its mechanism of action, immune-related adverse effects have been reported with this therapy. Despite increasing reports of immune-related adverse effects related to ipilimumab therapy, dermatomyositis associated with this agent has not previously been reported. OBSERVATIONS We describe a woman undergoing treatment with ipilimumab for metastatic melanoma who developed classic cutaneous findings of dermatomyositis along with proximal muscle weakness and elevated muscle enzymes. CONCLUSIONS AND RELEVANCE This case adds to the expanding literature regarding immune-related adverse events associated with ipilimumab. To our knowledge, drug-induced dermatomyositis from ipilimumab has not previously been reported. Physicians should be aware of these potential immune-related adverse events and consider drug-associated dermatomyositis in the differential diagnosis in patients receiving ipilimumab who present with a cutaneous eruption or muscle weakness.

Histopathologic Spectrum of Psoriasiform Skin Reactions Associated With Tumor Necrosis Factor-α Inhibitor Therapy. A Study of 16 Biopsies

Tumor necrosis factor (TNF)-α inhibitors (anti-TNF-α biologic drugs), currently used to treat different autoimmune conditions, may be associated with cutaneous drug reactions. New onset or worsening of psoriasis and psoriasis-like reactions have been reported in these patients. However, not much is known about the different histopathologic patterns of such skin lesions. The aim of this study was to evaluate the pathologic spectrum of clinically papulosquamous to pustular “psoriasiform” lesions in this setting. Sixteen biopsies from 9 patients on anti-TNF-α therapy for rheumatoid arthritis (n = 7), Crohn disease (n = 1), and Behçet disease (n = 1) who developed a “psoriasiform” skin rash during treatment were included in this study. None of the patients had history of psoriasis. Five patients (10 biopsies) showed a psoriasis-like pattern that varied from that seen in guttate lesions (4 biopsies), to well-established plaques (3 biopsies) to pustular psoriasis (3 biopsies). Three patients (4 biopsies) showed an interface/lichenoid dermatitis mimicking lichen planus. Two patients (2 biopsies) showed features of pustular folliculitis. Eosinophils varied from none (2 biopsies) to scattered (7 biopsies) to numerous (7 biopsies). Plasma cells were present in most cases. All pustular lesions had negative cultures. In conclusion, anti-TNF drugs elicit a spectrum of cutaneous reactions that go beyond the classical eosinophilic-rich hypersensitivity reaction and may closely mimic primary dermatitis. In addition to psoriasis-like lesions, lichen planus-like dermatitis and sterile pustular folliculitis should be included in the list of anti-TNF-α-related drug reactions. Because the different histopathologic findings may be subtle, clinical correlation is crucial to make the diagnosis.

Psoriatic alopecia/alopecia areata-like reactions secondary to anti-tumor necrosis factor-α therapy: a novel cause of noncicatricial alopecia.

With the increasing use of anti-tumor necrosis factor α (anti-TNF) biologic drugs to treat autoimmune diseases, an expanding array of adverse reactions is emerging. Anti-TNF drug-induced alopecia is a less well-known side effect of this class of drugs. The aim of this study was to define the clinical and histopathological features of alopecia arising in the setting of anti-TNF therapy. Clinical and histopathological features of 3 patients who developed scalp alopecia during anti-TNF treatment were examined. Two of the 3 patients also developed psoriasiform lesions outside the scalp, and biopsies from both scalp and nonscalp sites were reviewed. Clinically, each patient had large scaly patches associated with the scalp alopecia. All scalp biopsies revealed psoriasiform epidermal features and alopecia areata-like dermal changes. Epidermal changes included acanthosis and confluent parakeratosis with neutrophils and frank pustules. Dermal changes included markedly increased catagen/telogen and miniaturized hairs and peribulbar lymphocytic inflammation. Numerous plasma cells and eosinophils were present in all cases. Biopsies from the nonscalp lesions showed psoriasiform changes and prominent eosinophils and plasma cells. Two patients showed significant improvement of the alopecia with topical treatment only. In conclusion, anti-TNF therapy-related alopecia may closely mimic psoriatic alopecia and alopecia areata but can be histologically distinguished from alopecia areata by epidermal psoriasiform changes and dermal plasma cells and from primary psoriasis by the presence of plasma cells and eosinophils. A correct diagnosis can enable effective treatment and, in some cases, allow anti-TNF therapy to continue.

Cutaneous Dermatomyositis: An Updated Review of Treatment Options and Internal Associations

Dermatomyositis is a specific type of inflammatory myopathy with characteristic cutaneous findings. Patients may have skin disease without clinically apparent muscle disease, but this disorder is best thought of as a systemic process. Therefore, all patients with dermatomyositis skin lesions need appropriate evaluation for muscle disease, esophageal dysfunction, cardiopulmonary disease, and potential internal malignancy. There are many therapies that have been used for patients with dermatomyositis, but most are based upon case series or expert opinion rather than meta-analyses or randomized, placebo-controlled trials. Even those therapies that have been subjected to randomized, blinded, placebo-controlled trials include a mixture of patients with idiopathic inflammatory myopathy and do not utilize a validated assessment tool for measuring cutaneous disease responses. In this review, we discuss the therapies available as well as the internal associations with dermatomyositis.

Cumulative ultraviolet radiation flux in adulthood and risk of incident skin cancers in women.

Background:Solar ultraviolet (UV) exposure estimated based on residential history has been used as a sun exposure indicator in previous case–control and descriptive studies. However, the associations of cumulative UV exposure based on residential history with different skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), have not been evaluated simultaneously in prospective studies.Methods:We conducted a cohort study among 108 578 women in the Nurses’ Health Study (1976–2006) to evaluate the relative risks of skin cancers with cumulative UV flux based on residential history in adulthood.Results:Risk of SCC and BCC was significantly lower for women in lower quintiles vs the highest quintile of cumulative UV flux (both P for trend <0.0001). The association between cumulative UV flux and risk of melanoma did not reach statistical significance. However, risk of melanoma appeared to be lower among women in lower quintiles vs the highest quintile of cumulative UV flux in lag analyses with 2–10 years between exposure and outcome. The multivariable-adjusted hazard ratios per 200 × 10−4 Robertson–Berger units increase in cumulative UV flux were 0.979 (95% confidence interval (CI): 0.933, 1.028) for melanoma, 1.072 (95% CI: 1.041, 1.103) for SCC, and 1.043 (95% CI: 1.034, 1.052) for BCC.Conclusions:Associations with cumulative UV exposure in adulthood among women differed for melanoma, SCC, and BCC, suggesting a potential variable role of UV radiation in adulthood in the carcinogenesis of the three major skin cancers.

Dermatomyositis Induced by Anti–Tumor Necrosis Factor in a Patient With Juvenile Idiopathic Arthritis

IMPORTANCE Biologic therapies, including anti-tumor necrosis factor (TNF) agents, are increasingly used to treat a variety of autoimmune diseases. Paradoxically, these agents have been reported to induce some of the very diseases they were designed to treat, including dermatomyositis (DM). We describe the first case of anti-TNF-associated DM without muscle involvement presenting in an adult patient with a history of arthritis since childhood. This cutaneous eruption recurred after rechallenge with an alternate anti-TNF agent. OBSERVATIONS A 46-year-old man with juvenile idiopathic arthritis developed a pruritic cutaneous eruption while receiving etanercept. Given concern about a drug-induced eruption, etanercept therapy was discontinued and the cutaneous findings improved. However, after rechallenge with adalimumab, he developed similar findings consistent with the skin manifestations of DM. After discontinuation of all anti-TNF drug therapy and the addition of methotrexate sodium, his eruption improved. CONCLUSIONS AND RELEVANCE Because the use of these agents is increasing, practitioners should be aware of the possibility of anti-TNF-induced autoimmune disorders, including DM. The case described herein is unique in that anti-TNF-induced autoimmune disease occurred in a patient with existing arthritis since childhood and recurred with rechallenge, adding further evidence to support the existence of anti-TNF-induced DM.

Treatment Options for Pityriasis Rubra Pilaris Including Biologic Agents: A Retrospective Analysis From an Academic Medical Center

Treatment Options for Pityriasis Rubra Pilaris Including Biologic Agents: A Retrospective Analysis From an Academic Medical Center Pityriasis rubra pilaris (PRP) is characterized by hyperkeratotic papules, palmoplantar keratoderma, and widespread erythema with islands of sparing. Treatment is challenging, and a standard therapeutic protocol does not exist. Given the paucity of available therapeutic data, we assessed the clinical presentation of PRP and clinical response (CR) to therapy at 2 teaching hospitals in Boston, Massachusetts. In addition, we aimed to determine the role of systemic and biologic agents.

Psoriasiform reactions to anti-tumor necrosis factor α therapy.

ObjectiveGiven increasing concern about the adverse effects of anti–tumor necrosis factor &agr; (anti–TNF-&agr;) medications, we sought to characterize psoriasiform eruptions in patients on these medications. MethodsIn a retrospective review of patients at the Brigham and Women’s Hospital combined dermatology-rheumatology clinic, we identified 13 patients (1 male and 12 female patients) who developed psoriasiform eruptions while on anti–TNF-&agr; medications. ResultsInciting medications were adalimumab, etanercept, and infliximab. Patients were on their inciting medication for a median time of 24 months and a mean time of 31.3 months before developing eruptions. Five of 7 patients experienced complete resolution of lesions with topical corticosteroids and discontinuation of anti–TNF-&agr; medications with the remaining 2 patients having partial improvement. One of the other 6 patients experienced complete resolution with topical corticosteroid treatment only, with the remaining 5 patients experiencing partial improvement. After changing anti–TNF-&agr; agents, 1 patient had partial improvement of psoriasiform lesions, and 7 patients had no improvement. ConclusionsAll of the main anti–TNF-&agr; medications currently used are capable of causing psoriasiform eruptions. Poor responders to topical agents, such as corticosteroids, may benefit from supplemental therapy aimed at the psoriasiform eruption or changing to a different class of immunomodulatory agents. Switching anti–TNF-&agr; medications had a low likelihood of improving psoriasiform skin reactions, further suggesting that these eruptions are a drug class effect.

Epidemiology and Treatment of Eosinophilic Fasciitis: An Analysis of 63 Patients From 3 Tertiary Care Centers

Author Contributions: Drs Hubiche and Valério had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hubiche, Valério, del Giudice. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Hubiche, Valério, del Giudice. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Hubiche, Valério. Administrative, technical, or material support: Hubiche, Mahe, Phan. Study supervision: Hubiche, Boralevi, Bodemer Skandalis, del Giudice.