Atypical Conjunctival Lesion as the Initial Presentation of Granulomatosis With Polyangiitis in an Adolescent Male

Purpose: The purpose of this study was to report the first case of a conjunctival granulomatous lesion as the presenting sign of granulomatous polyangiitis (GPA) in a pediatric patient. Methods: This study is a case report. Results: A 14-year-old Hispanic boy presented with a conjunctival lesion on the inferior bulbar conjunctiva of the right eye associated with diffuse conjunctival injection. The mass progressively grew and became painful over the course of 6 weeks. No retinal or orbital abnormalities were noted on examination. The lesion was excised, and histopathological analysis was consistent with granulomatous inflammation. The lesion recurred after 15 months, and a second excisional biopsy was performed. The lesion again slowly recurred, and on presentation to our clinic, an elevated lesion in the inferior limbal/bulbar conjunctiva of the right eye was noted from 4 to 8 o'clock with accompanying forniceal shortening. Five months after the second excision, the patient developed flu-like symptoms with polyarthralgia. A full diagnostic workup revealed multiple pulmonary nodules on chest imaging, proteinuria on urinalysis, and a positive c-antineutrophil cytoplasmic antibody on serological studies. Based on these findings, the patient underwent a kidney biopsy which showed pauci-immune crescentic glomerulonephritis, consistent with a diagnosis of GPA. The patient achieved disease remission with rituximab. Despite treatment, the conjunctival lesion did not regress and remained unchanged in size for 3 years with periodic episodes of inflammation. Conclusions: This is the first documented case of a conjunctival mass as the initial presenting feature of pediatric GPA. The presence of granulomatous inflammation on histopathology and recurrences after excision should raise suspicion for GPA in children and adults

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases

BACKGROUND. Undifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments. METHODS. Sixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing. RESULTS. Thirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome–like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody–positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS. CONCLUSIONS. In patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18–mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5–autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression