Reactive Neutrophilic Dermatoses in Adult-Onset Immunodeficiency due to Interferon-Gamma Autoantibody and Their Associated Factors

Abstract

<b><i>Background:</i></b> Adult-onset immunodeficiency (AOID) due to interferon-gamma autoantibody is a rare, acquired immunodeficiency disease. Reactive neutrophilic dermatoses (RND), predominantly Sweet syndrome (SS), and generalized pustular eruption have been reported repeatedly. <b><i>Objectives:</i></b> The aims of this study were to describe the cutaneous manifestations in AOID patients and determine the incidence of RND and associated factors using a larger population size than have been previously reported. <b><i>Methods:</i></b> A retrospective chart review of all confirmed AOID cases in Chiang Mai University Hospital from January 2006 to June 2020 was conducted. The demographics and characteristics of RND including type, onset, and laboratory information in every episode of cutaneous manifestations were collected. Generalized estimating equations of binary logistic regression were used to determine the indicators of RND. <b><i>Results:</i></b> A total of 146 patients with confirmed AOID were identified. Of these, 57 cases (39%) developed at least one episode of RND. Thirteen cases (23%) of the patients experienced RND twice during the follow-up period. All recurrence of RND displayed the same cutaneous phenotype, with the exception of 2 cases who had both SS and generalized pustular eruption. Finally, 49 episodes of SS and 22 episodes of generalized pustular eruption were included in the analysis. All patients with RND had concomitant active opportunistic infections, of which most were non-tuberculous mycobacterium (NTM) infection. NTM infection (prevalence odds ratio [POR] 2.87), lymphadenopathy (POR 3.30) as well as lower serum alkaline phosphatase (ALP) level (POR 0.71 for every 100-unit increment in ALP) were found to be significantly associated with RND occurrence. <b><i>Conclusions:</i></b> 39% of our AOID patients experienced RND once during the course of the disease. Notable factors associated with RND occurrence were concomitant NTM infection, lymphadenopathy, and lower level of ALP.

Comparative immunohistochemical analysis of inflammatory cytokines in distinct subtypes of Sweet syndrome

“…Given that opportunistic infections, and particularly NTM, could be a potential cause of AOID-associated SS by triggering inflammatory conditions ( 8 ), we investigated the effects of NTM infection on the expression of various cytokines using IHC analysis. A significant increase in IHC positivity in both IFN-γ and IL-17 in AOID-associated SS with NTM ( p = 0.003 and p < 0.001, respectively) and without NTM ( p < 0.001 and p < 0.001, respectively) was observed compared to the control group ( Table 3 ; Figure 2B ).…”

“…Recent studies have revealed that SS has become a more common cutaneous manifestation reported in adult-onset immunodeficiency (AOID) ( 7 , 8 ). The presence of potent and neutralizing autoantibodies which act against IFN-γ are recognized as a cause of AOID ( 9 ), leading to an increased susceptibility to infections ( 10 ).…”

Human Leukocyte Antigen Markers for Distinguishing Pustular Psoriasis and Adult-Onset Immunodeficiency with Pustular Reaction

“…Pustular psoriasis (PP) and related pustular skin disorders are immune-mediated diseases consisting of several clinical entities including localized pustular psoriasis, mainly palmoplantar pustular psoriasis (PPP) and acrodermatitis continua of Hallopeau (ACH), generalized pustular psoriasis (GPP), a life-threatening form of psoriasis, and acute exanthematous generalized pustular eruption (AGEP), a severe subtype of drug hypersensitivity [ 1 ]. These entities are recognized by the presence of multiple pustules as a result of extensive neutrophilic accumulation [ 1 , 2 , 3 ]. The sterile pustular eruptions noted in 20–30% of patients with adult-onset immunodeficiency (AOID) are particularly noteworthy.…”

“…The resultant immunodeficiency in AOID patients manifests similarly to AIDS, with patients being susceptible to a range of opportunistic infections (OIs) typically seen in those with severely compromised immune systems [ 4 ]. This phenomenon has been extensively studied, with reactive neutrophilic dermatoses being identified as a common feature in AOID due to the anti-IFN-γ autoantibody [ 2 ]. Furthermore, a variety of reactive and infective dermatoses, including Sweet’s syndrome, have been associated with AOID [ 5 ].…”