Drew J.B. Kurtzman

Metastatic Crohn's disease: A review and approach to therapy

Metastatic Crohns disease (CD) is a rare cutaneous manifestation of CD that was first described nearly 50 years ago. Many subsequent reports have defined its most common clinical and histopathologic features. The pathogenesis underlying metastatic CD is unknown but various hypotheses exist. An established standard therapy is lacking. Owing to its rarity and nonspecific clinical presentation along with the diversity of inflammatory skin disorders that often complicate CD, the diagnosis of metastatic CD may be overlooked. This report highlights the salient features of this disorder to facilitate recognition and management of this rare dermatosis.

A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab and tildrakizumab for the treatment of moderate to severe plaque psoriasis

Abstract Objective: To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis. Methods and results: Twenty-four randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82–29.54, p < .00001) and 14.55 (10.42–20.31, p < .00001) for ustekinumab 90 mg, 13.75 (8.49–22.28, p < .00001) and 9.81 (5.70–16.89, p < .00001) for ustekinumab 45 mg, 17.65 (12.38–25.17, p < .00001) and 26.13 (16.05–42.53, p < .00001) for secukinumab 300 mg, 15.36 (10.76–21.94, p < .00001) and 20.91 (12.82–34.13, p < .00001) for secukinumab 150 mg, 18.22 (10.63–31.23, p < .000001) and 18.82 (10.36–34.16, p < .00001) for ixekizumab 80 mg every 4 weeks, 19.83 (11.07–35.52, p < .00001) and 20.41 (11.01–37.81, p < .00001) for ixekizumab 80 mg every 2 weeks, 14.79 (9.86–22.16, p < .00001) and 21.93 (15.52–31.01, p < .00001) for brodalumab 210 mg, 11.55 (7.77–17.18, p < .00001) and 16.59 (11.72–23.49, p < .00001) for brodalumab 140 mg, 12.40 (8.87–17.34, p < .00001) and 10.84 (7.91–14.85, p < .00001) for guselkumab 100 mg, 11.45 (7.45–17.58, p < .00001) and 10.97 (6.44–18.69, p < .00001) for tildrakizumab 200 mg, 11.02 (7.17–16.93, p < .00001) and 10.03 (6.45–15.59, p < .00001) for tildrakizumab 100 mg. Similar outcomes were seen for PASI-90. Safety was satisfactory for each therapy at any dose, but a slightly increased risk of withdrawal due to toxicity was observed in individuals receiving ixekizumab compared to placebo. Conclusion: Ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab were highly efficacious and generally well-tolerated when used as treatments for moderate to severe plaque psoriasis.

A Blistering Response: Concurrent Psoriasis and Pemphigus Foliaceus

PRESENTATION A 62-year-old woman’s dermatologic difficulties were compounded when light treatment for psoriasis spurred pemphigus foliaceus; an occurrence very rarely noted in the medical literature. She presented with an erythematous, crusted eruption involving her entire head and neck and most of her trunk. The lesions developed several months after consecutive exposures to narrowband ultraviolet B (UVB) phototherapy for chronic plaque psoriasis (Figure 1).

Anti-melanoma differentiation–associated gene 5 (MDA5) dermatomyositis: A concise review with an emphasis on distinctive clinical features

&NA; Melanoma differentiation–associated gene 5 (MDA5) is a recently described autoantigen target in a subset of patients with dermatomyositis. Anti‐MDA5 dermatomyositis is characterized by a unique mucocutaneous and systemic phenotype that includes cutaneous and oral ulceration, painful palmar papules, alopecia, panniculitis, arthritis, a lower incidence of myositis, and, importantly, an elevated risk of interstitial lung disease with a potentially fatal course. Because the clinical features can differ substantially from those typically observed in cutaneous dermatomyositis, the diagnosis is often overlooked, which might negatively affect patient outcomes. This review aims to familiarize the clinician with the distinctive clinical features of anti‐MDA5 dermatomyositis in order to enhance its recognition and to facilitate an appropriate screening and management strategy.

Approach to and Management of the Neutrophilic Dermatoses

The neutrophilic dermatoses are a related set of disorders that share common features. These disorders are not directly related to infection and are considered forms of “sterile” neutrophilic inflammation. They can occur with an associated systemic disease or as a primary cutaneous process. Subcorneal pustular dermatosis, Sweet’s syndrome, erythema elevatum diutinum, bowel-associated dermatosis-arthritis syndrome, pyoderma gangrenosum, and neutrophilic eccrine hidradenitis represent the most common of these disorders. This review highlights the salient features of the neutrophilic dermatoses with an emphasis on clinical features, evaluation, and management.

Neuromalignancy complicating the Muir–Torre syndrome

Keywords: brain cancer; hereditary nonpolyposis colorectal cancer; immunohistochemistry; Muir–Torre syndrome; sebaceous neoplasm

Muir-Torre Syndrome and Central Nervous System Malignancy: Highlighting an Uncommon Association.

Muir–Torre syndrome (MTS) is an uncommon cancer syndrome characterized by the development of cutaneous and visceral neoplasms. The majority of cases are familial exhibiting an autosomal dominant inheritance pattern and occur as a result of germline mutations involving the mismatch repair (MMR) genesMSH2,MLH1,MSH6, or PMS2. These mutations produce microsatellite instability that eventuates in tissue carcinogenesis. Sporadic MTS is rare and is distinguished from the heritable form by the preservation ofMMR function and absence ofmicrosatellite instability and has been reported exclusively in immunocompromised individuals. Although the severity and expression of MTS vary, common to all forms is the universal development of skin and visceral tumors. The former includes sebaceous adenoma, epithelioma and carcinoma, which are almost pathognomonic for the disorder, andkeratoacanthomawith sebaceous features. Internal malignancy, the major cause of disease morbidity and mortality, most frequently arises from the gastrointestinal and genitourinary tracts and, less commonly, the breast, head and neck, and bone marrow. Only 6 cases of malignant brain tumors occurring in MTS have been documented. This report describes a case of inherited MTS complicated by neuromalignancy and highlights this important, albeit rare, association by brief review of the literature. A46-year-oldwhitemansoughtdermatologic evaluation in late 2001 for an enlarging lesion on his right scalp. Histopathologic examination demonstrated an atypical adnexal neoplasm with sebaceous differentiation consistent with a sebaceous carcinoma. Tumor immunohistochemistry studies revealed a loss ofMSH2 andMSH6 gene product expression, and a provisional diagnosis of the MTS was rendered. He underwent Mohs micrographic surgery without recurrence of the tumor. A thorough review of his family history noted many members affected by internal malignancy (Figure 1).

Psoriasis and Psoriatic Spectrum Disease: A Primer for the Primary Care Physician

Psoriasis is a chronic, immune-mediated disorder that affects approximately 7.5 million people in the United States. Individuals with psoriasis may develop cutaneous, articular, and systemic manifestations, which are a source of significant morbidity and a heightened risk of mortality, and may adversely impact patient-reported quality of life measures. Psoriasis is now recognized as a risk factor for cardiovascular disease, metabolic syndrome, peripheral vascular disease, inflammatory bowel disease, certain malignancies, and chronic renal disease. Therefore, it has become increasingly relevant that primary care physicians have a basic working knowledge and an understanding of fundamental management principles of psoriasis. This review highlights the salient clinical features of psoriasis and psoriatic spectrum disease, emphasizing key updates with respect to systemic disease and associated conditions, and briefly outlines a therapeutic algorithm for the primary care physician.

Factors Associated with Advanced Stage Merkel Cell Carcinoma at Initial Diagnosis and the Use of Radiation Therapy: Results from the National Cancer Database

Background: The stage of disease at initial diagnosis and the use of radiation therapy (RT) are important determinants of survival in patients with Merkel cell carcinoma (MCC). Objective: To define factors that are associated with advanced‐stage MCC at the time of initial diagnosis and the use of RT. Methods: Cross‐sectional, retrospective analysis of patients with MCC registered in the National Cancer Database during the period from 2004 to 2013. Results: A total of 11,917 patients were identified; 3152 and 4586 patients were excluded from the staging and RT analyses, respectively, because of lack of available data. African American ethnicity (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.06‐2.10; P = .023), lack of medical insurance (OR, 2.15; 95% CI, 1.40‐3.30; P < .001), Charlson‐Deyo comorbidity score of at least 1 (OR, 1.21; 95% CI, 1.09‐1.34; P < .001), residence more than 26 miles from a treatment facility (OR, 1.18; 95% CI, 1.03‐1.35; P = .015), tumor located on the lower limb/hip (OR, 1.59; 95% CI, 1.42‐1.78; P < .001) or trunk (OR, 2.05; 95% CI, 1.81‐2.33; P < .001), and poorly (OR, 2.57; 95% CI, 1.13‐5.82; P = .024) or undifferentiated (OR, 3.11; 95% CI, 1.36‐7.15; P = .007) tumor histology predicted advanced‐stage MCC at the time of initial diagnosis. The use of RT was associated with Native American ethnicity (OR, 5.04; 95% CI, 1.10‐22.99; P = .037), tumor size between 1.5 and 2.7 cm (OR, 1.27; 95% CI, 1.10‐1.47; P = .001), electing not to have surgery (OR, 2.77; 95% CI, 1.90‐4.03; P < .001), positive postsurgical margins (OR, 1.39; 95% CI, 1.18‐1.63; P < .001), and receiving treatment at a comprehensive cancer program (OR, 1.25; 95% CI, 1.03‐1.50; P = .020). Limitations: Retrospective design limits generalizability of the results, and precise details of RT regimens utilized were not available. Conclusions: A number of factors are associated with advanced‐stage MCC at initial diagnosis and the use of RT. Health care models should account for these factors, and efforts should be directed toward improving those that are modifiable.

A Violaceous, Photodistributed Cutaneous Eruption and Leg Ulcer in a Woman With Essential Thrombocytosis

A 69-year-old woman presented for the evaluation of a slowly progressive, asymptomatic cutaneous eruption on her hands and forearms, as well as an enlarging, painful ulcer on her left leg that developed 6 months earlier. Her medical history was notable for essential thrombocytosis, which had been complicated by portal vein thrombosis, and she had been receiving treatment with hydroxyurea and rivaroxaban for the past 2 years. Despite worsening cutaneous disease, she otherwise felt well and denied associated fevers, weakness, weight loss, myalgias, arthralgias, or other constitutional symptoms. Physical examination revealed atrophic and reticulated violaceous plaques with a striking photoaccentuated distribution on the patient’s dorsal hands and forearms (Figure, A). Scaly, violaceous plaques were also present on the thenar eminences and radial aspects of her first 2 fingers bilaterally (Figure, B). Prominent poikiloderma was seen on her sunexposed chest and neck, and a large, stellate ulcer was present on her left distal lower leg (Figure, C). A lesional skin biopsy was performed on the patient’s left forearm (Figure, D). Violaceous scaly plaques B Violaceous reticulated plaques A