Ramazan Erdem

University of Health Science, Faculty of Medicine, Antalya Training and Research Hospital, Department of Hematology, Antalya, Türkiye

Erdem R. Hypergammaglobulinemic Purpura of Waldenström. In: Kurt Yüksel M, editor. Autoinflammatory Diseases in Hematology from Diagnosis to Treatment. 1^st ed. Ankara: Türkiye Klinikleri; 2025. p.191-196.

ABSTRACT

Waldenström Hypergammaglobulinemic Purpura (HGPW), first described by Waldenström in 1943, is a syn-drome characterized by recurrent purpura in the lower extremities, elevated erythrocyte sedimentation rate (ESR), polyclonal gammopathy, and mild anemia. HGPW predominantly affects young women of reproductive age (18-40 years), accounting for approximately 80% of cases. Clinically, the condition manifests with mild itch-ing, burning, and tingling, accompanied by characteristic skin findings, such as petechiae and larger purpuric lesions, most commonly on the lower extremities. These skin lesions typically resolve spontaneously within a few days but may leave residual pigmentation after repeated episodes. Lesions recur at intervals of days, weeks, or months, often for years. Purpuric episodes may be triggered by heat exposure, tight clothing, prolonged standing, and alcohol consumption. The pathogenesis of Waldenström’s hypergammaglobulinemic purpura re-mains unclear. Hypergammaglobulinemia appears to play a significant role, as circulating immune complexes (CIC), often containing rheumatoid factor IgG or IgA, are frequently detected in patient serum. These circulating immune complexes (CIC) accumulate in the walls of dermal blood vessels, causing vascular damage. Histo-pathologically, early-stage lesions exhibit inflammation of superficial dermal blood vessels with polymorphonu-clear leukocyte infiltration. However, biopsies performed after 24 hours typically reveal only chronic mononu-clear cell infiltrates. HGPW may present as a primary (idiopathic) disorder or as secondary to an underlying condition, most frequently Sjögren’s syndrome, and less commonly systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, hepatitis C, or cystic fibrosis. Rarely, it may be associated with hematologic malignancies such as monoclonal gammopathy, lymphoma, or multiple myeloma. Polyclonal hypergammag-lobulinemia is the most distinctive laboratory finding, with additional abnormalities including elevated ESR, mild anemia, leukopenia, and rheumatoid factor. Anti-Ro (SSA) antibodies are also commonly observed, alt-hough not universally. Platelet counts and coagulation tests are typically within normal limits. Diagnosing HGPW can be challenging, as its symptoms resemble those of other hemorrhagic disorders. Differential diagno-ses include cryoglobulinemic purpura, Waldenström macroglobulinemia, Henoch-Schönlein purpura, and throm-bocytopenic purpura. HGPW is of particular concern during pregnancy, as maternal anti-Sjögren’s syndrome (SSA)/Ro antibodies (with or without anti-SSB/La antibodies) may cross the placenta, potentially resulting in fetal heart block or neonatal lupus in the infant. Treatment for HGPW is not always necessary, and no standard-ized therapeutic approach exists. In some instances, plasmapheresis has been employed to reduce circulating immune complexes, although it provides only transient improvement in cutaneous lesions. Corticosteroids have shown limited efficacy. When HGPW is associated with systemic rheumatic diseases, systemic steroids or im-munosuppressive agents may be warranted to manage the underlying condition. Traditional treatments include aspirin, dipyridamole, colchicine, dapsone, hydroxychloroquine, and indomethacin. In pregnant patients, caution is advised to avoid unnecessary medications due to the potential teratogenic risks of many drugs, particularly immune modulators. Plasmapheresis remains a potentially safe and effective option to reduce plasma viscosity by lowering elevated IgG levels.

Keywords: Vasculitis; Leukocytoclastic; Cutaneous; Purpura; Hypergammaglobulinemia