Pustular psoriasis (PuP) is a rare variant of psoriasis, presenting with non-follicular pustules on top of inflamed skin. It is mainly classified into generalized PuP (GPP) and localized PuP, of which the latter includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). 1 While PuP manifests in adulthood in most patients, in some patients, PuP manifests before 18 years of age and is known as juvenile-onset PuP (JPP).While most cohorts agreed in terms of female predominance in patients, the mean age of onset varied with each population and subtype, falling between the late twenties and late forties. In addition, diabetes mellitus and hypertension are also commonly found among PuP patients. 2

Adult-onset immunodeficiency syndrome (AOID) with anti-interferon (IFN)γ autoantibodies is characterized by an AIDS-like illness with disruptive IFNγ signaling. Patients generally present with recurrent and disseminated opportunistic infections along with neutrophilic dermatoses. Generalized pustular psoriasis (GPP; Online Mendelian Inheritance in Man #614204) is characterized by acute generalized erythema and scaling with numerous aseptic pustules. Mutations in SERPINA3 have been reported as predisposing risk factors for both AOID and GPP. Here, we report two unrelated patients, one with AOID and a pustular skin reaction and the other with GPP, who both carried the same heterozygous variant c.718G>A (p.Val240Met) in SERPINA1. Our observation of a shared mutation in SERPINA1 in AOID and GPP indicate possible pathobiological and disease mechanism similarities in these two disorders. Thus, variants in both SERPINA1, SERPINA3, and potentially other SERPIN family members may be associated with the etiology of GPP and AOID.

Sweet syndrome (SS) has been increasingly reported in patients with adult-onset immunodeficiency (AOID) due to anti-interferonγ autoantibody who also have concomitant opportunistic infections, especially disseminated non-tuberculous mycobacterial infection (dNTMI). A retrospective study retrieving data from 2011 through 2020 was conducted. We compared clinical characteristics of SS with and without AOID and generated the prediction model and examined the interaction between AOID and dNTMI in the occurrence of SS. Lymphadenopathy, pustular lesions, and leukocytosis are the significant predictors for AOID-associated SS. Adjusted risk differences were 0.58 (95% confidence interval [CI], 0.33-0.83), 0.21 (95% CI, 0.02-0.39), and 0.24 (95% CI, 0.01-0.47), respectively. Based on the analysis of aggregated cross-sectional data, both the overall and the direct effect of AOID increased the prevalence of SS. The indirect effect of AOID on the occurrence of SS might also be mediated through dNTMI or other common opportunistic infections. In addition, there was a trend of positive additive interaction between AOID and dNTMI. Although the test of additive interaction did not reveal statistically significant results, a deviation from additivity of isolated effects might suggest potential causal interaction between AOID and dNTMI. The distinctive clinical syndrome comprising lymphadenopathy, pustular lesions, and leukocytosis in patients with SS should raise the awareness of clinicians to the potential of underlying AOID.

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<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.