The use of checkpoint inhibitors for treatment of advanced malignancies is increasing. Rashes, pruritus, and more rarely, reactions resembling Stevens‐Johnsons syndrome (SJS) or toxic epidermal necrolysis (TEN) may occur secondary to checkpoint inhibitors. To characterize existing literature on these reports, we queried the PubMed/MEDLINE database for cases of SJS or TEN associated with checkpoint inhibitors. We identified 18 cases of SJS or TEN‐like reactions to checkpoint inhibitors in the literature. There were 12 cases of SJS‐like rashes with median time to onset of 5.6 weeks (average of 8.9 weeks), of which five were delayed to week 8 or later from checkpoint inhibitor initiation. The five TEN‐like reactions had a median time to onset of 4 weeks (average of 5.38 weeks), of which two were delayed to week 6 or later. SJS/TEN‐like reactions to nivolumab (seven cases) had median onset time of 3 weeks, whereas five cases secondary to pembrolizumab had median onset time of 11 weeks. Seven cases in this study described prodromal rashes, which varied from localized papular rashes to generalized morbilliform rashes, prior to evolution into SJS or TEN‐like patterns. SJS‐like patterns generally improved well on systemic treatment/supportive care and no cases of death were identified, but mortality occurred in three of five patients with TEN‐like reactions. Dermatologists should consider the possibility for unique features of SJS/TEN in response to checkpoint inhibitors. Additional studies will be necessary to further characterize SJS/TEN‐like eruptions on checkpoint inhibitors and determine the optimal management of these cases.

eneralized pustular psoriasis (GPP) is an orphan disease characterized by the rapid appearance of sterile pustules and generalized erythema. Patients are often systemically ill and may experience severe organ dysfunction and rarely death. The genetic risk factors for pustular psoriasis are different from other types of psoriasis. To date, variations have been identified in the following genes: IL36RN (interleukin-36 receptor antagonist), CARD14 (caspase recruitment domain family member 14), AP1S3 (adapter related protein complex 1 subunit sigma 3), SERPINA3 (serpin family A member 3), and MPO (myeloperoxidase); however, the majority of patients do not have a known genetic variant. 1 Owing to the rarity of GPP, there is limited information about the natural disease course. The only epidemiological data from the United States is a report of 63 patients seen over 29 years at a single institution. 2 The objective of this study is to describe the clinical characteristics, natural disease course, treatments, and health care utilization of patients with GPP across the United States. Methods Study Design and PopulationThis is a retrospective, longitudinal case series of adults (≥18 years) with a diagnosis of GPP confirmed by a dermatologist (January 1, 2007-December 31, 2018) (Table 1). Up to 5 potential cases were identified from each of 20 participating sites' electronic health records or site-specific databases, starting with cases seen most recently. All diagnoses were confirmed by the principal investigator at each site at the time of data entry. Only patients who met the European Rare and Severe Psoriasis Expert Network (ERASPEN) consensus definition of GPP with documentation of "primary, sterile, macroscopically visible pustules on nonacral skin, excluding cases where pustulation is restricted to psoriatic plaques" 3 and had had a dermatology encounter with active pustular disease during the study period were included.IMPORTANCE Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data.OBJECTIVE To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. DESIGN, SETTING, AND PARTICIPANTSA retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. MAIN OUTCOMES AND MEASURESThe primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization.RESULTS Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) rep...

Myelin change in CMT4J recapitulates the features of acquired demyelinating neuropathies. This pathology is not Schwann cell autonomous. Instead, it relates to systemic processes involving interactions of multiple cell types and abnormally elevated intracellular Ca . Injection of a Ca chelator into Fig4 mice improved segmental demyelination, thereby providing a therapeutic strategy against demyelination. Ann Neurol 2018;83:756-770.

Checkpoint inhibitors are a new class of drugs that enhance the immune system's intrinsic ability to destroy tumor cells by blocking signaling through the programmed cell death (PD‐1) receptor, its ligand (PD‐L1), and the cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4). The resulting increase in immunologic activity is responsible for a variety of adverse cutaneous reactions, which sometimes include neutrophilic dermatoses. We queried the PubMed database for existing cases of checkpoint inhibitors causing neutrophilic dermatoses. The literature search identified four cases of Sweet syndrome, four cases of pustular eruptions, two cases of pyoderma gangrenosum, and one case of bullous lupus erythematosus secondary to checkpoint inhibitors. All neutrophilic dermatoses were treated with topical or systemic steroids and most (9 of 11) completely resolved. Dermatologists should be aware of these rare, adverse cutaneous reactions to checkpoint inhibitors and how to approach their treatment, especially as their use increases.

Drug reaction and eosinophilia with systemic symptoms (DRESS), also known as drug‐induced hypersensitivity syndrome (DIHS), shares features with hemophagocytic lymphohistiocytosis (HLH), most notably fever, rash, and internal organ involvement. However, there is increasing recognition of drug‐induced (secondary) HLH and biopsy‐proven hemophagocytosis in DRESS, suggesting that HLH and DRESS not only overlap but also may be diseases on the same spectrum of immune dysfunction. To characterize existing literature on HLH/DRESS overlap, we queried the PubMed/MEDLINE database for 23 cases of HLH‐DRESS codiagnosis. Average time‐to‐onset of rash after exposure to inciting drug was 2.7 weeks. Fourteen cases (61%) clinically worsened despite initial therapy, prompting a workup with diagnosis of HLH on average 2.3 weeks after diagnosing DRESS. Nine cases met HLH diagnostic criteria and had a RegiSCAR score ≥4. Nine cases met one set of criteria with a presentation suggestive of the other. Five cases met neither criteria. A patient presenting with fever, generalized rash, bicytopenia, and internal organ involvement after drug exposure was most predictive of meeting diagnostic criteria for both HLH and DRESS. Treatment was highly variable, although most initiated systemic corticosteroids with/without IVIG, plasmapheresis, or etoposide. Patients with poor outcomes in this review were treated using steroid monotherapy and had viral reactivation. Dermatologists should consider the possibility of HLH in any patient presenting with fever, rash, internal organ involvement, and cytopenia. Additional studies will be necessary to further characterize HLH and DRESS overlap and determine optimal management.

ObjectiveThe SCN11A gene encodes the NaV1.9 sodium channel found exclusively in peripheral nociceptive neurons.MethodsAll enrolled participants were evaluated clinically by electrophysiologic studies, DNA sequencing, and punch skin biopsies.ResultsAll affected family members are afflicted by episodes of pain. Pain was predominantly nociceptive, but not neuropathic in nature, which led a diagnosis of fibromyalgia in some patients. All patients had normal findings in nerve conduction studies for detecting large nerve fiber neuropathies and skin biopsies for detecting small nerve fiber pathology.ConclusionsUnlike those patients with missense mutations in SCN11A, small fiber sensory neuropathy, and neuropathic pain, the Arg225Cys SCN11A in the present study causes predominantly nociceptive pain with minimal features of neuropathic pain and undetectable pathophysiologic changes of peripheral neuropathy. This finding is consistent with dysfunction of nociceptive neurons. In addition, since nociceptive pain in patients has led to the diagnosis of fibromyalgia, this justifies a future search of mutations of SCN11A in patients with additional pain phenotypes such as fibromyalgia to expand the clinical spectrum beyond painful small fiber sensory neuropathy.

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