Background/Purpose: WHIMS (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome) is a rare autosomal dominant primary immunodeficiency due to gain of function mutations of the CXC chemokine receptor 4 (CXCR4). CXCR4 signaling is crucial in hematopoietic stem cell homeostasis, and plays an important role in innate and adaptive immune responses. The disease often manifests with recurrent bacterial infections and Human Papilloma Virus (HPV)-induced warts of the hand, feet and genitals. The focus of our study is to characterize the rheumatological manifestations in WHIMS patients.

Methods: Nine patients out of 36 diagnosed with WHIM syndrome enrolled in a treatment protocol were assessed. These 9 patients were identified owing to rheumatological complaints. Demographics, clinical presentation, laboratory data and imaging studies were tabulated to look for common characteristics and patterns of presentation.

Results: The majority of our cohort had onset of rheumatological complaints as children or young adults. Six out of nine were female. The spectrum of initial complaints ranged from arthralgia to overt arthritis. The pattern of joint involvement included asymmetric or symmetric oligo- or polyarthritis involving small and large joints. Three patient exhibited symptoms after a known trigger. In one case, an Oligoarticular small and large joint arthritis postdated a positive urethral chlamydia PCR. Three patients had presentation satisfying a retrospective diagnosis of juvenile idiopathic arthritis. Only one patient had septic arthritis. Another had idiopathic avascular necrosis of the hip in the childhood. We observed that four patients had worsening of joint symptoms temporally related to the treatment of the primary disease. Two patients had tenosynovitis involving the fingers leading to deformity. Auto-antibodies were negative in all eight patients and none were HLA B27 positive. Arthrocentesis data was available in two patients and revealed inflammatory synovial fluid. One of the patients underwent synovial biopsy demonstrating chronic synovitis with T and B lymphocytes. Overall, the response to NSAIDs was variable. Sulfasalazine was used in two of the five patients for purposes of steroid sparing with partial benefit.

Conclusion: Rheumatological manifestations have not previously been reported as a major component of the clinical manifestation of WHIM syndrome. We present the first detailed cataloguing of such manifestations in a cohort of WHIM patients. Our finding of a high prevalence of joint findings warrants further study. The etiology of arthritis in WHIM syndrome is unknown but could relate to impaired clearance of infectious organisms associated with arthritis or alternatively, an increased risk for autoimmune disease. The rheumatological management of these patients is challenging due to the underlying immunodeficiency.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatic-manifestations-of-whim-syndrome/