002112 - Heterozygous IL6ST Mutation–Associated Rare Primary Immunodeficiency: A Case Report

Background

Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by recurrent bacterial and fungal infections, eczema, eosinophilia, and markedly elevated serum IgE levels. While classically associated with STAT3 mutations, heterozygous mutations in IL6ST (gp130) have been shown to cause a STAT3-HIES–like phenotype through a dominant-negative mechanism, due to impaired IL-6/IL-11–mediated STAT3 signaling.

Case 

A 32-year-old male patient with known diagnoses of diabetes mellitus (DM) and hidradenitis suppurativa (HS), and with third-degree parental consanguinity, was referred by the dermatology department with a preliminary diagnosis of PID due to recurrent abscess-like, purulent skin lesions refractory to antibiotic therapy. The patient had a 20-year history of DM and had been followed for HS for the past 2 years under rifampicin and clindamycin treatment. For approximately 12 years, he had experienced recurrent abscesses involving the entire body—predominantly the anterior and posterior trunk, axillary regions, scrotum, and gluteal area—despite prolonged hospitalizations requiring intravenous antibiotic therapy and repeated abscess drainage procedures.

Investigations were initiated with a suspicion of PID. Fifteen teeth had previously been extracted due to presumed gingival and soft tissue infections. Apart from these findings, no additional clinical features suggestive of PID were present. There was no history of chronic disease or early death among siblings.

Skin biopsy obtained from the dorsal region (Figure) revealed hyperkeratosis, mild accentuation of the granular layer, perivascular active–chronic inflammation in the dermis, and early sclerotic changes. Abscess cultures grew Klebsiella spp. and Staphylococcus aureus, while acid-fast bacilli staining was negative. Immunological evaluation demonstrated reduced IgG2 levels and elevated total IgE (Table). Genetic analysis identified a heterozygous mutation in the IL6ST gene (c.2315del; p.Pro772ArgfsTer16). IVIG therapy at a dose of 40 g every 21 days was initiated. After 3 months of IVIG treatment, no reduction in abscess formation or antibiotic requirement was observed; therefore, interferon-gamma therapy (0.1 mg, three times weekly) was commenced. The patient is currently being followed under this treatment.

Conclusion

This case highlights that heterozygous IL6ST mutations can result in an HIES phenotype resembling STAT3-HIES. Recognition of IL6ST-related immunodeficiency is essential for accurate diagnosis and appropriate management. Genetic testing should be considered in patients with atypical or treatment-refractory HIES features, and therapeutic strategies largely parallel those used in STAT3-HIES.