Regorafenib is a second-generation multikinase inhibitor that is approved for the treatment of metastatic colon cancer and advanced gastrointestinal stromal tumors. Hand-foot skin reaction, alopecia, and oral mucositis are well-established side effects of this medication. Herein, we discuss a 60-year-old woman who developed a lobular and septal granulomatous panniculitis after six months of therapy with regorafenib. Biopsy demonstrated focal lobular and septal granulomatous inflammation admixed with septal fibrosis and lobular lymphohistiocytic infiltrate associated with fat necrosis. To our knowledge, regorafenib-induced panniculitis has not been previously described. Increased awareness of this presentation can facilitate more timely diagnosis and treatment.

Kaposi sarcoma typically presents as violaceous macules and papules in immunocompromised, specifically HIV-positive, patients. Its distinct clinical features often facilitate rapid diagnosis. In this article, we report a case of Kaposi sarcoma presenting as a concerning yet nondescript lesion in an HIV-negative woman. Although Kaposi sarcoma is frequently part of the differential diagnosis for skin lesions affecting HIV-positive patients, it is less frequently considered in HIV-negative individuals. Additionally, this case differs from the classic clinical presentation of Kaposi sarcoma by resembling a squamous cell carcinoma or superficial basal cell carcinoma. Therefore, it illustrates the importance of suspicious lesion biopsies to ensure accurate diagnosis and appropriate treatment.

We present a rare case of dermatomyositis associated with nivolumab therapy for melanoma. Nivolumab is an immune checkpoint inhibitor that blocks the programmed death-1 (PD1) receptor and has a number of associated immunotherapy related adverse events. Although most are T-cell mediated, some are antibody mediated mimics of classical autoimmune diseases. We review the characteristics of other cases of anti-PD1 associated dermatomyositis and the recent literature to better understand how to classify and treat this challenging immunotherapy related adverse event.

With recent advancements in the understanding of vitiligo pathogenesis, Janus kinase (JAK) inhibitors have emerged as a promising new treatment modality, but their effects remain incompletely elucidated. Tofacitinib, an oral JAK 1/3 inhibitor approved for the treatment of rheumatoid arthritis, has previously been shown to induce significant re-pigmentation in vitiligo. However, as with other novel targeted therapies, cutaneous adverse effects have been observed. We report a 36-year-old woman with a history of rheumatoid arthritis, refractory to multiple pharmacotherapies, who was initiated on tofacitinib and subsequently developed progressive depigmented patches consistent with new-onset vitiligo. Although definitive causation cannot be established in this case without additional studies, it is important to note that many targeted therapies have the potential to induce paradoxical effects, that is, the occurrence or exacerbation of pathologic conditions that have been shown to respond to these medications. Paradoxical findings with other targeted therapies include the occurrence of melanoma during treatment with BRAF inhibitors, keratoacanthomas with PD-1 inhibitors, vitiligo and psoriasis with TNF-alpha inhibitors, and hidradenitis suppurativa with various biologic agents. Although JAK inhibitors hold therapeutic promise in the treatment of inflammatory skin disorders, further research is warranted to more fully comprehend their effects.

Nontuberculous mycobacteria are pathogens with diverse manifestations in immunocompromised hosts. The lesser-known Mycobacterium haemophilum usually causes cutaneous infection. Diagnosis is challenging but is aided by molecular testing and multidisciplinary communication. We present an immunocompromised patient with disseminated cutaneous mycobacterial infection with digital tenosynovitis.

Treatment of cancer with EGFR inhibitors is limited by on-target skin toxicities induced by inhibition of the MAPK pathway. BRAF inhibitors are known to paradoxically activate the MAPK downstream of EGFR, which we confirmed using human skin keratinocytes. We then conducted a phase I clinical trial testing the hypothesis that topical therapy with the BRAF inhibitor LUT014 could improve skin toxicities induced by EGFR inhibitors. Ten patients with metastatic colorectal cancer who had developed acneiform rash while being treated with cetuximab or panitumumab were enrolled in three cohorts. LUT014 was well tolerated, and there were no dose-limiting toxicities. The acneiform rash improved in the 6 patients who started with grade 2 rash in the low and intermediate cohorts. We conclude that topical LUT014 is safe and efficacious in improving rash from EGFR inhibitors, consistent with the mechanism of action inducting paradoxical MAPK activation. SIGNIFICANCE: BRAF inhibitor topical therapy could avoid dose reductions of EGFR inhibitors, locally treating the main dose-limiting skin toxicity of this class of agents.This article is highlighted in the In This Issue feature, p. 2113.