Pathogenic variants in PSTPIP1 enhance pyrin inflammasome activation, leading to overproduction of interleukin-1 (IL-1). These variants are associated with autoinflammatory syndromes such as PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) and PAMI (PSTPIP1-associated myeloid-related proteinemia inflammatory) syndrome. We report a pediatric case presenting an oligosymptomatic and previously under-recognized phenotype.
The patient is the first child of a non-consanguineous couple. His father has a history of childhood-onset neutropenia and chronic treatment-refractory acne. At 7 months of age, the child developed a lesion at the Bacillus Calmette–Guérin (BCG) vaccination site, treated empirically with isoniazid despite lack of microbiological confirmation. Initial immunologic evaluations—including immunoglobulins, lymphocyte subsets, and dihydrorhodamine—were normal.
At age 6, he presented with transient synovitis, intermittent fever, recurrent adenitis, hepatosplenomegaly, and myalgia. After age 10, he developed reactivation of the BCG site (deltoid cellulitis), persistent hepatosplenomegaly, and bicytopenia (iron-refractory anemia and neutropenia). Elevated acute-phase reactants (C-reactive protein and erythrocyte sedimentation rate) were noted, while immunologic workup—including IL-12/IFN-γ receptor expression—was normal. Bone marrow aspirate showed no abnormalities.
Due to persistent inflammation, whole exome sequencing was performed at age 13, revealing a PSTPIP1 variant (c.748G>A, autosomal dominant), previously associated with PAMI syndrome and classified as likely pathogenic. Markedly elevated MRP8/14 levels (>25,000 ng/mL) supported this diagnosis. Plasma zinc results are pending.
Currently, the patient experiences moderate myalgias (with normal CPK [creatine phosphokinase]) and mild persistent neutropenia. Functional assays assessing inflammasome activation and interferon signatures are underway to guide personalized treatment.
This case broadens the clinical spectrum of PSTPIP1-associated autoinflammatory diseases, suggesting that PAMI syndrome may manifest with mild or oligosymptomatic phenotypes in childhood. Early genetic and functional investigations may help avoid diagnostic delay and inform targeted therapy strategies.
