Combination therapy of prednisolone and mizoribine improves cryoglobulinemic vasculitis with purpura and skin ulcers.

Conventional treatment is not standardized for hepatitis C virus-negative cryoglobulinemia, but corticosteroids, immunosuppressive agents, and plasma exchange typically improved the symptoms. Mizoribine is an immunosuppressive agent that was developed in Japan and has been found to inhibit the proliferation of lymphocytes, especially B cells. We have encountered an elder patient who had hepatitis C virus-negative, type II cryoglobulinemic vasculitis with leg purpura and skin ulcers. Her symptoms improved and cryoglobulin disappeared by the combination therapy of prednisolone and mizoribine. We speculate the action mechanism of this therapy is due to immunosuppressive effects including up-regulation of the efficacy of prednisolone by mizoribine.

Hypergammaglobulinemic purpura in two sisters with Sjogren's syndrome responding to colchicine treatment.

Purpura is the hallmark of hypergammaglobulinemic purpura (HP). It appears mainly after strenuous activity in the dependent areas of the body. Treatment is mostly symptomatic. Here we report two sisters with Sjogren's syndrome (SS) and HP who had a remarkable response to colchicine treatment.

Hypergammaglobulinaemic purpura associated with IgG subclass imbalance and recurrent infection.

We describe a child who initially presented with recurrent infections. He subsequently developed hypergammaglobulinemic purpura but responded well to corticosteroids and hydroxychloroquine.

Hypergammaglobulinemic purpura associated with Sjögren's syndrome and chronic C type hepatitis.

Although hypergammaglobulinemic purpura usually occurs secondarily on the lower legs in several disorders, purpura has also recently been reported to be associated with chronic C type hepatitis (HCV). To define the differences in the clinical, histological and laboratory findings and the prognosis of hypergammaglobulinemic purpura associated with those two disorders, we examined ten patients with hypergammaglobulinemic purpura, 6 patients with hypergammaglobulinemic purpura associated with Sjögren's syndrome (SjS) and 4 patients with hypergammaglobulinemic purpura with chronic C type hepatitis. Five of 6 patients with SjS were female. Attacks of purpura occurred in the pretibial area in all cases. Triggering factors included long walks and prolonged standing. The mean duration of attacks was 6.4 days. No systemic manifestations were associated. Anti-Ro/SS-A and anti-La/SS-B antibodies were expressed in one case. Spontaneous regression was noted in all cases; however, recurrence was noted in one. On the other hand, all the 4 patients with hypergammaglobulinemic purpura associated with HCV were men. Purpura was indurated in a few cases. Involved sites included the knee, forearm, abdomen and thigh in addition to the lower leg. The mean duration of attacks was 12.6 days. Recurrent purpura was noted in one case. Cryoglobulin was positive in three cases. In one patient with severe recurrent purpura, attacks stopped with prednisolone 10 mg/day. Histologically, leukocytoclastic vasculitis was detected in three cases associated with SjS and two cases with HCV. In conclusion, hypergammaglobulinemic purpura associated with HCV appears to occur unilaterally with a sex predilection for men and the manifestations last longer than those associated with SjS. Severe palpable purpura was also noted in association with HCV; systemic prednisolone resulted in good control.

Hypergammaglobulinemic purpura in systemic autoimmune rheumatic diseases: predictive value of anti-Ro(SSA) and anti-La(SSB) antibodies and treatment with indomethacin and hydroxychloroquine.

OBJECTIVE: To define the clinical manifestations, autoantibody associations, optimal treatment, and prognosis of hypergammaglobulinemic purpura associated with systemic autoimmune rheumatic diseases. METHODS: Of 303 consecutive patients with systemic autoimmune rheumatic diseases evaluated over 5 years, 17 French Canadian patients with hypergammaglobulinemic purpura with systemic lupus erythematosus (SLE) (n = 12) or another systemic autoimmune rheumatic disease (n = 5) were identified and followed prospectively. Mild secondary Sjörgren's syndrome developed in 9 (53%) patients. RESULTS: Sixteen (94.1%) patients were women. Attacks of hypergammaglobulinemic purpura occurred in the pretibial (76.5%) or perimalleolar (70.5%) areas or the dorsal aspect of the feet (52.9%). Triggering factors included walking, prolonged standing, and alcohol intake. The mean duration of attacks was 6.1 days. Systemic manifestations consistent with a flare of the underlying systemic autoimmune rheumatic diseases accompanied hypergammaglobulinemic purpura attacks in 15 (88%) patients. Arthralgias (n = 13, 86.6%), arthritis (n = 9, 69.2%), and periarthritis were characterstically localized adjacent to the purpura. Anti-Ro antibodies were expressed in all (100%) patients with hypergammaglobulinemic purpura with SLE, but in only 11 (28.9%) of 38 consecutive patients with SLE without hypergammaglobulinemic purpura (P < 0.000001, odds ratio 84, 95% confidence interval 4.6, 1525). The positive predictive values for hypergammaglobulinemic purpura in SLE were: anti-Ro plus anti-La 73%, anti-La 57%, and anti-Ro 52%. The negative predictive value of anti-Ro was 100%. Although 11 (92%) patients with SLE with anti-Ro expressed anti-52 kDa Ro [4 (36.3%) of whom also expressed anti-60 kDa Ro], this frequency was not greater than in anti-Ro positive patients with SLE without hypergammaglobulinemic purpura. The effects of indomethacin or hydroxychloroquine were assessed over 6 months in 8 patients with recurrent incapacitating hypergammaglobulinemic purpura. Complete (n = 4) or partial (n = 4) remission of hypergammaglobulinemic purpura occurred. In 5 additional patients with severe hypergammaglobulinemic purpura, attacks stopped with prednisone 25 to 60 mg daily. The mean duration of hypergammaglobulinemic purpura followup was 5.4 years (range 1-6 years). At last followup, hypergammaglobulinemic purpura had resolved in 11 (64.7%) patients despite persistently abnormal serology. CONCLUSION: In the absence of anti-Ro antibodies, a presumptive diagnosis of hypergammaglobulinemic purpura secondary to SLE should be questioned. Prednisone should be used only in severe hypergammaglobulinemic purpura. Indomethacin and hydroxychloroquine are of value in the treatment of milder hypergammaglobulinemic purpura.

Benign hypergammaglobulinemic purpura in a patient with ulcerative colitis and peripheric arthritis.

A 32-year-old patient is described presenting with ulcerative colitis and oligoarthritis who later developed benign hypergammaglobulinemic purpura. This diagnosis was confirmed by clinical investigation, immunological findings as well as by histological and immunofluorescent examination. He was successfully treated with steroids and azathioprin. The relevant literature is reviewed.

Benign hypergammaglobulinemic purpura of Waldenström associated with Sjögren's syndrome. Case report and review of immunologic aspects.

Since its first description, fewer than 150 cases of benign hypergammaglobulinemic purpura of Waldeström have been reported. There is a preponderance of females with this disorder, which is characterized by long-standing purpuric vasculitic lesions usually in the lower extremities, increased sedimentation rate, anemia, leukopenia, and hyperglobulinemia with a normal clotting process. Numerous associations have been shown between this and other systemic disorders such as Sjögren's syndrome, systemic lupus erythematosus, a rheumatoid arthritis. A 40-year-old woman is described who had an 18-year history of recurrent purpura and increased IgG levels. Skin biopsy showed acute vasculitis, and immunofluorescent study revealed fibrinogen precipitation and C3 deposition. Serologic evaluation demonstrated the presence of rheumatoid factor and antinuclear antibodies (1:80). Raji assay showed increased circulating immune complexes, and the T cell subsets were normal. The purpura was associated with symptoms and physical findings of Sjögren's syndrome. On the basis of serologic and skin biopsy findings, an autoimmune origin of the disease is postulated.

Cutaneous leukocytoclastic vasculitis with hyperglobulinemia and splenomegaly. A variant of hyperglobulinemic purpura of Waldenström.

Patient with hepatosplenomegaly and recurrent small purpuric lesions of cutaneous leukocytoclastic vasculitis was found to have a polyclonal elevation of gamma-globulin and a persistently elevated ESR. Circulating immune complexes were detected that support the concept of a postulated immune complex pathogenesis. Indomethacin therapy was ineffective, but prednisone therapy resulted in notable clinical improvement and the return of elevated immunoglobulin levels to the normal range. Patients with hyperglobulinemic purpura, which may be a subset of leukocytoclastic vasculitis, should be examined for associated conditions.

[New results on hyperglobulinemic purpura of Waldenström in childhood (author's transl)]. / Neue Befunde bei der benignen Purpura hypergammaglobulinaemica Waldenström im Kindesalter.

The case of a 13 year old girl with benign purpura hypergammaglobulinemica Waldenström. Besides the characteristic clinical symptoms and the respective laboratory results new findings we demonstrated, which might shed some light into the pathogenesis of this disease. The transformation rate of lymphocytes was decreased particularly after stimulation with ConA. The T-lymphocytes which are reduced in their function are unable to sufficiently control the activity of mesenchymal cells which results in an increased production of glycosaminoglycans. The demonstration of glycosaminoglycan-inclusion-bodies in the mononuclear bone marrow cells of the patient could be explained by the above mentioned mechanism. Upon therapy with D-penicillamine the clinical state improved along with a reduction of the sedimentation rate, the serum protein and the serum gamma-globulin.

Chronic active hepatitis and ulcerative colitis associated with eosinophilia, nonthrombocytopenic hypergammaglobulinemic purpura and serologic abnormalities.

A patient with chronic active hepatitis (CAH) and ulcerative colitis (UC) associated with eosinophilia, nonthrombocytopenic hypergammaglobulinemic purpura and serologic abnormalities is presented. Abnormal liver function, gastrointestinal and systemic symptoms as well as the associated epiphenomena responded dramatically to oral corticosteroid therapy. The remission was maintained during an eight month follow-up period with low dose prednisone therapy.

Purpura hyperglobulinemica (Waldenstrom).

A case of hyperglobulinemic purpura of Waldenstrom with involvement of trunk and arms of 10 years duration has been presented. The patient had mild anemia, hepatosplenomegaly, positive rheumatoid factor and no evidence of immonological abnormalities associated for with systemic lupus erythematosus. A brief review of clinical manifestation and pathogenesis is cited.