Skin Manifestations in Patients with Adult-onset Immunodeficiency due to Anti-interferon-gamma Autoantibody: A Relationship with Systemic Infections

Abstract

Adult-onset immunodeficiency due to anti-interferon-γ autoantibody is an emerging acquired immunodeficiency with frequent skin manifestations. A retrospective chart review was conducted and identified 41 patients with the syndrome. Skin involvement was detected in 33 (80%) patients, 15 (45%) with infective skin diseases and 27 (82%) with reactive skin disorders. Reactive lesions were mostly neutrophilic dermatoses, e.g. Sweet syndrome. Of note, the presence of neutrophilic dermatoses was highly associated with infections of other sites. An adjusted odds ratio for the existence of infections in patients with neutrophilic dermatoses was 14.79 (95% CI: 5.13, 42.70; p < 0.001). Moreover, neutrophilic dermatoses were significantly correlated with opportunistic infections observed in those with defects in cell-mediated immunity including non-tuberculous mycobacterium and disseminated fungal infection. The odds ratio for opportunistic infections in the presence of neutrophilic dermatoses was 12.35 (95% CI: 5.00, 30.55; p <0.001). Thus, the presence of neutrophilic dermatoses in patients with the syndrome can signal opportunistic infections that warrant physician attention.

Triple infection with Cryptococcus, varicella-zoster virus, and Mycobacterium abscessus in a patient with anti-interferon-gamma autoantibodies: a case report

“…Genetically inherited disorders of the IFN-γ pathway lead to overwhelming infections by intracellular pathogens, such as Cryptococcus, VZV, and nontuberculous mycobacteria, which is similar to the etiology in our case. Additionally, the majority of patients with auto-IFN-γ AAbs were reported to be Southeast Asians [1,2,[4][5][6][7][8], which is strongly suggestive of an inherited predisposition. These patients were shown to be strongly associated with HLA-DRB1 and HLA-DQB1 [9], which suggests that the development of AAbs to IFN-γ may be similar to those observed in other HLA-linked autoimmune diseases.…”

Efficacy of acitretin in the treatment of reactive neutrophilic dermatoses in adult‐onset immunodeficiency due to interferon‐gamma autoantibody

“…To date, the pathophysiology of reactive neutrophilic dermatoses in patients with AOID remains to be elucidated, including the response to OI, an overactivation of innate immunity to compensate for any defect in the CMI pathway and the dysregulation of cytokine pathways involving T‐helper (Th)1 cytokines or the interleukin‐23/Th17 axis . These proposed hypotheses may result in aggregation and accumulation of neutrophils in the skin.…”

“…The most common organ involvement reported in patients with AOID is lymph node, followed by skin and soft tissue . Skin manifestations are categorized into skin infection and reactive dermatoses, particularly neutrophilic dermatoses, including Sweet syndrome, generalized pustular eruption and neutrophilic lobular panniculitis . Most of the time, these neutrophilic reactive dermatoses occur concurrently with active OI, predominantly disseminated NTM infection …”

“…The drugs used in the treatment of these reactive neutrophilic dermatoses associated with AOID include systemic and/or topical corticosteroids, colchicine, dapsone, non‐steroidal anti‐inflammatory drugs, methotrexate and, rarely, acitretin . Acitretin, a second‐generation systemic retinoid, displays an inhibitory property of neutrophil migration, leading to several reports of its benefit in the treatment of neutrophilic dermatoses, particularly subcorneal pustular dermatosis, even in the absence of AOID .…”

Phenocopies: Mimics of Inborn Errors of Immunity

“…In laboratory studies, patients have elevated CRP and ESR during the infectious period in addition to leukocytosis. Despite intensive antibiotic treatment, more than half of the patients will continue with persistent infection, in patients with this characteristic the duration of treatment can vary from 206 to 1439 days [67] [68].…”