Adult Henoch-Schönlein Purpura in a Patient With Myelodysplastic Syndrome and a History of Follicular Lymphoma
Henoch-Schönlein purpura (HSP) is a systemic leukocytoclastic vasculitis involving arterioles and venules most commonly in the skin, glomeruli, and gastrointestinal tract. In skin, it is associated with IgA deposition around dermal blood vessels. While an exact cause of HSP has not been elucidated, several processes have been implicated in its development, including infections; drugs; and allergic, rheumatologic, and neoplastic diseases. We present a 57-year-old woman with a history of follicular lymphoma who developed HSP likely associated with myelodysplastic syndrome. This case is clinically significant because the patient was thought to be in remission of her hematologic disease until her skin findings prompted further evaluation. Her diagnosis of HSP was based on clinical presentation with palpable purpura and abdominal pain, and was confirmed with biopsy and immunohistochemical analyses of purpuric papules demonstrating leukocytoclastic vasculitis and strong anti-IgA labeling in the dermal endothelial cells consistent with immunocomplex deposition. The occurrence of vasculitis and malignant disease in the same patient often is difficult to interpret, as some patients may exhibit both diseases independently and by chance, while others may have vasculitis as a paraneoplastic syndrome. We review cases of adult HSP associated with malignancy in the literature.
Ten days after discharge, the patient's cutaneous eruption had greatly improved, with residual macules present on the dorsum of both feet and only faint reticulated erythema and rare purpura across the lower abdomen and lower extremities. She was scheduled for a second stem cell transplant to treat the myelodysplasia.
Comment
HSP is a systemic leukocytoclastic vasculitis involving arterioles and venules most commonly in the skin, glomeruli, and gastrointestinal tract.1,2 It is common for affected tissues to histologically demonstrate the presence of IgA in vessel walls. Fever and palpable purpura, predominantly on the buttocks and extremities, often are the first signs of HSP and may be accompanied by arthralgia, abdominal pain, and renal disease.2 The arthritis can be characterized as transient and oligoarticular, commonly affecting large joints and often with pain out of proportion to objective evidence of synovitis.2 Signs of peritoneal inflammation may occur and melena is common; more severe gastrointestinal tract complications that may warrant surgical intervention also have been described.2,3 Renal pathology in patients with HSP involves a spectrum ranging from mild focal glomerulitis to rapidly proliferative glomerulonephritis accompanied by variable amounts of proteinuria and hematuria.2 In 1990, the American College of Rheumatology identified 4 criteria for separating HSP cases from controls: (1) age 20 years or younger at disease onset, (2) palpable purpura, (3) acute abdominal pain, and (4) biopsy showing granulocytes in the walls of small arterioles or venules. When 2 or more of any of these criteria were present, HSP was distinguished from other forms of vasculitis with a sensitivity of 87.1% and a specificity of 87.7%.2 HSP is the most common systemic vasculitis of childhood and has been historically and predominantly viewed as a pediatric disease. HSP is believed to affect adults less frequently but has been reported to be responsible for a substantial percentage of all cases of cutaneous vasculitis among adults.4 In a retrospective study of patients with HSP, Blanco et al5 found that HSP represents a more severe clinical syndrome in adulthood than in childhood, but the prognosis of patients is equally good in both adult and pediatric populations. An exact cause of HSP has not been identified; however, many processes have been implicated in its development, including infections; drugs; and allergic, rheumatologic, and neoplastic diseases. Neoplasia in adults with systemic or cutaneous vasculitis has an estimated prevalence of 2.5% to 5.0%, with hematopoietic malignancies occurring more commonly than solid tumors.6 Although malignancy has been reported to occur in association with nearly all forms of vasculitis, the association between cutaneous hypersensitivity vasculitis and hematopoietic malignancies is most notable.7 In 1996, Fortin8 outlined several classic hypotheses explaining the role of neoplastic disease in the development of vasculitic syndromes such as HSP, including the impaired clearance of normally deposited immune complexes, abnormal production of immunoglobulins that may either directly react to vascular antigens and cause in situ immune complex formation or form circulating immune complexes that can then deposit in vessel walls, and common antigens presenting on the surface of malignant cells that may stimulate T-cell activation or the production of immunoglobulin directed not only toward malignant cells but healthy epithelium as well. The association of vasculitis with malignancy has been reviewed extensively in the literature.9-12 Sanchez-Guerrero et al9 found that 11 of 222 patients with vasculitis had associated neoplasia, with both hematologic and solid tumors implicated. Importantly, the authors noted that in 4 of 11 patients with paraneoplastic vasculitis, symptoms of vascular inflammation were evidence of the initial presentation of neoplasia or its recurrence.9 Kurzrock et al10 reviewed the manifestation of vasculitis in patients with solid tumors and found that in 71% of cases (25/35), symptoms of vasculitis appeared before or concurrent with the initial recognition or relapse of the tumor. Greer et al11 described 13 patients with both vasculitis and lymphoproliferative or myeloproliferative syndromes and reported a statistically significant (P<.0000001) association between the 2 when compared with all other tumors. The authors further asserted that tumor-associated vasculitis is a heterogeneous group of syndromes that share clinical features; malignancy or its recurrence should be considered in patients with unexplained vasculitis; and although treatment of the underlying neoplasm may lead to resolution of vasculitis, specific therapy for vascular inflammation often is not effective.11
HSP specifically has been described in patients with malignancy and vasculitis (Table).6,13-36 In 2000, Pertuiset et al6 reviewed 14 cases of adult HSP and found malignant neoplasm in 4 cases. They also identified 15 reports of adult HSP with malignant disease in the literature. Collectively, these 19 cases were compared with 158 adults who had HSP but no malignancy. The authors reported that 63% (12/19) of neoplasms associated with adult HSP were solid tumors, while the remaining 37% (7/19) were hematologic malignancies. Patients with paraneoplastic HSP were older, more likely to be male, more frequently had joint involvement, and had a lower frequency of prior infection compared with patients with HSP not associated with malignancy. There was no reported statistically significant difference in percentage of patients with cutaneous purpura, gastrointestinal tract involvement, renal involvement, or polyclonal IgA increase between the 2 groups.6
