Faculty Bibliography

Sarcoidosis is a chronic, multisystem, inflammatory disorder of unknown etiology that is characterized by noncaseating granulomas that impair normal organ functioning. Sarcoidosis predominantly affects the lungs, but the skin is often cited as the second most frequently involved organ. Cutaneous manifestations of sarcoidosis are highly variable and ongoing research seeks to better understand the relationship between clinical morphology and disease prognosis. Skin findings in patients with sarcoidosis can be "specific," in which sarcoidal granulomas infiltrate the skin, or they can represent a "nonspecific" reactive inflammatory process, as is seen in calcinosis cutis and erythema nodosum. Cutaneous sarcoidosis can be the initial presenting sign or develop later in the course of the disease. In some patients, the skin will be the most involved and impactful organ system and will drive therapy. In other cases, the skin will be an incidental or minor finding, but may be easily accessible for biopsy to confirm the diagnosis. There are many potential therapies for sarcoidosis, though no one therapy is universally effective.

Pyoderma gangrenosum (PG) is a rare, and often challenging to diagnose, inflammatory disorder with relatively high rates of morbidity and mortality. Central to the diagnosis of PG is histologic evaluation and exclusion of other entities. Large-scale studies investigating the proportion of patients receiving a thorough diagnostic work-up, as well as prevalence studies regarding comorbidities and systemic treatment in PG using claims-based data, are sparse. Our objective was to identify patients diagnosed with PG and describe the diagnostic work-up and prevalence of common comorbidities and therapies in this population using claims-based data in a retrospective cohort study. In order to better understand practices of diagnostic work-up, we captured rates of skin biopsy, tissue culture, and/or surgical debridement prior to initial diagnosis. We also identified the prevalence of PG-associated comorbidities and initial immunosuppressive therapy given for PG. Of the 565 patients diagnosed with PG, 9.4% underwent skin biopsy, 8% tissue culture, and 1.4% both skin biopsy AND tissue culture prior to diagnosis. Inflammatory bowel disease was the most prevalent comorbidity (16.3%). The most common treatment administered was systemic corticosteroids (17%). Although practice guidelines explicitly delineate histology and exclusion of infection as important diagnostic criteria, only a minority of patients in this study underwent skin biopsy and/or tissue culture prior to receiving a diagnosis of PG, suggesting that patients may receive a diagnosis of PG without having tissue evaluation. Such discordance between practice guidelines and "real-world" practice inevitably increases the risk for misdiagnosis of PG and misdirected treatment with immunosuppressants for presumptive PG in cases of PG mimickers. Moreover, comorbidities associated with PG may occur, or be identified in, a lower proportion of patients as compared with what is reported in the existing literature. Study limitations include a population restricted to < 65 years with commercial insurance and the reliance upon ICD diagnostic coding to capture the population.

Dermatomyositis (DM) is an autoimmune connective tissue disease that most commonly affects skin and muscles. Clinical manifestations can be protean, with some patients experiencing skin-limited disease while others develop serious systemic complications including interstitial lung disease (ILD). While both T cell-mediated and humoral immune dysregulation have been purported to play a role in manifesting said end-organ damage, our understanding of immunophenotypic prognostic factors associated with the development of ILD in DM patients remains limited. Thus, we sought to identify potential biomarkers that might be differentially expressed in lesional skin obtained from DM patients with versus without ILD. Utilizing NanoString technology, we assessed differential mRNA expression of 800 immune-related genes in formalin-fixed, paraffin-embedded lesional skin samples obtained from five DM patients with ILD compared to five DM patients without ILD. Among 42 highly regulated genes, 10 were significantly (p<0.05) upregulated in DM patients with ILD: CD44, NFKBIZ, CD24, EGR1, DEFB103B, CCL18, CCL22, CXCL2, S100A8 and S100A9. Notably, serum levels of S100A8/A9 heterodimer (an endogenous ligand of Toll-like receptor 4) are known to correlate with clinical severity in patients with DM-associated ILD, thereby supporting NanoString's utility in identifying salient genes associated with end-organ damage in DM. We also identified several novel genes downregulated in patients with DM-associated ILD that play a role in autophagy and adaptive immune activation: CLEC7, LEF1, KLRC2, BTLA, MUC1, and TCF7. Taken together, our results begin to characterize an immune-related gene expression signature in lesional DM skin that may be associated with comorbid ILD. While validation experiments are ongoing, the identification of biomarkers of systemic disease in lesional DM skin not only has the potential for risk stratifying DM patients at the time of tissue diagnosis but may provide novel targets for early intervention against DM-associated ILD.
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Sarcoidosis is a multisystem disorder of unknown etiology characterized by accumulation of granulomas in affected tissue. Cutaneous manifestations are among the most common extrapulmonary manifestations in sarcoidosis and can lead to disfiguring disease requiring chronic therapy. In many patients, skin disease may be the first recognized manifestation of sarcoidosis, necessitating a thorough evaluation for systemic involvement. Although the precise etiology of sarcoidosis and the pathogenic mechanisms leading to granuloma formation, persistence, or resolution remain unclear, recent research has led to significant advances in our understanding of this disease. This article reviews recent advances in epidemiology, sarcoidosis clinical assessment with a focus on the dermatologist's role, disease pathogenesis, and new therapies in use and under investigation for cutaneous and systemic sarcoidosis.

BACKGROUND:As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS:In this IRB-approved retrospective case series, biopsies of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS:Twelve cases were included. Histopathological features from two injection site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsies came from generalized eruptions that demonstrated interface changes consistent with an exanthematous drug reaction. Three biopsies revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS:Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid. This article is protected by copyright. All rights reserved.