Sulfasalazine-induced Angioimmunoblastic lymphadenopathy developing in a patient with juvenile chronic arthritis

We describe a patient with juvenile chronic arthritis who developed reactive angioimmunoblastic lymphadenopathy, induced by sulfasalazine. Development of angioimmunoblastic lymphadenopathy although rare, is a very serious side effect of sulfasalazine treatment, and patients treated with this drug should be watched carefully. Received: 10 April 2000 / Accepted: 16 June 2000     

Angioimmunoblastic lymphadenopathy with malignant transformation during long-term remission of ocular melanoma

A 52-year-old woman presented with angioimmunoblastic lymphadenopathy five years after undergoing enucleation for ocular melanoma. She was first treated by corticotherapy and azathioprine and had two successive remissions over an 18-month period. Lymph node biopsy performed when lymphadenopathy relapsed for the second time showed focal malignant transformation of angioimmunoblastic lymphadenopathy. Intensive polychemotherapy induced a complete remission. Three months after completion of chemotherapy, the patient presented with hepatic metastases from her melanoma and died shortly thereafter. This is believed to be the first documented association between angioimmunoblastic lymphadenopathy and melanoma. Issues regarding the relationship between angioimmunoblastic lymphadenopathy and nonlymphoid malignancies are raised.     

Monoclonal hypergammaglobulinemia without malignant transformation in angioimmunoblastic lymphadenopathy with dysproteinemia

A patient with angioimmunoblastic lymphadenopathy with dysproteinemia had a monoclonal IgG hypergammaglobulinemia. In contrast to previous reports, the development of a monoclonal paraprotein in the setting of angioimmunoblastic lymphadenopathy with dysproteinemia did not herald a transformation to malignancy. The patient improved clinically and the monoclonal gammopathy disappeared when the patient was treated with prednisone. The relationship of these findings to current concepts regarding the cause of angioimmunoblastic lymphadenopathy with dysproteinemia is discussed.     

B-immunoblastic lymphoma arising in angioimmunoblastic lymphadenopathy

We present a female patient with a B-immunoblastic lymphoma of the IgM-lambda type arising in angioimmunoblastic lymphadenopathy. An increased ratio of helper/inducer to suppressor/cytotoxic lymphocytes in the lymph node could have triggered the proliferation of B cells. Evolution of IgM cryoglobulinemia was paralleled by malignant transformation in the lymph node. A short-term in vitro chemosensitivity test could predict response to COP combination chemotherapy suggesting that in vitro chemosensitivity testing can be useful for the therapeutic management of angioimmunoblastic lymphadenopathy.     

Scabies-associated angioimmunoblastic lymphadenopathy

A systemic disorder characterized by fever and reactive lymphadenopathy developed in a patient with scabies infestation. Regression of all clinical symptoms and signs occurred after antiscabies therapy. Two months later, the whole clinical picture reappeared concomitantly with scabies reinfestation. Subsequent lymph node biopsy demonstrated typical angioimmunoblastic lymphadenopathy (AILD). It is plausible that persistent antigenic stimulation caused by scabies infection was of pathogenetic importance in the induction of the syndrome of AILD. Infectious agents should be considered and looked for in patients with AILD, since they may play a role in the evolution of this disease.     

Synovitis in angioimmunoblastic lymphadenopathy with dysproteinemia simulating rheumatoid arthritis

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia who developed a symmetric, rheumatoid-like, peripheral polyarthritis. Radiographs of the involved joints revealed soft tissue swelling without erosions or cartilage loss. Rheumatoid factor and fluorescent antinuclear antibodies were negative, and C-reactive protein and erythrocyte sedimentation rate were normal. Synovial fluid analysis showed an inflammatory effusion (white blood cell count of 3,500/mm3, with 76% polymorphonuclear leukocytes). A closed synovial biopsy of the wrist revealed a mononuclear infiltrate consistent with angioimmunoblastic lymphadenopathy with dysproteinemia. Monthly parenteral chemotherapy treatment with high-dose methyl-prednisolone and cyclophosphamide resulted in remission of all manifestations of disease, including arthritis.     

Nodular regenerative hyperplasia of the liver, peliosis hepatis, and perisinusoidal fibrosis. Association with angioimmunoblastic lymphadenopathy and severe hypoxemia

Three different liver lesions were found in a 20-year-old woman with angioimmunoblastic lymphadenopathy. The lesions included nodular regenerative hyperplasia of the liver, perisinusoidal fibrosis, and peliosis hepatis. It is suggested that the association of angioimmunoblastic lymphadenopathy with this broad spectrum of liver lesions was not fortuitous.     

Immunoblastic lymphadenopathy occurring during treatment with carbamazepine. 2 cases

Dysimmune lymphadenopathies during carbamazepine treatment. A report of two cases. We report on two cases of dysimmune lymphadenopathies with histological aspect of angio immunoblastic lymphadenopathy (AIL) developing after administration of carbamazepine. Clinical manifestations consisted of fever, erythroderma, generalized pruritus, facial edema, lymphadenopathy, liver enlargement. The two patients had anemia, hypogammaglobulinemia, impaired liver function and a negative Coomb's test. Lymphocyte stimulation test with carbamazepine in vitro was positive in both cases. Lymph node biopsy disclosed the angioimmunoblastic proliferation characteristic of AIL. After discontinuing carbamazepine, a complete remission was obtained.     

Studies on viral etiology of angioimmunoblastic lymphadenopathy

Plasma samples of patients with angioimmunoblastic lymphadenopathy (AIBL) were tested for anti-HTLV antibodies and for interferon content. Out of 12 patients 4 had antibodies to HTL-III. Two of these plasma samples contained antibodies reacting with HTLV-I and HTLV-II, too. Activated interferon (IFN) system was found in patients with clinical remission of AIBL, as it was detected by IFN titration in their plasma samples. Data suggest the etiological role in AIBL of virus(es) related to the HTLV family.     

Angioimmunoblastic lymphadenopathy associated with polyarthritis.

A patient with angioimmunoblastic lymphadenopathy with dysproteinaemia is described. The patient had a severe clinical illness with a pronounced haemolytic anaemia, which followed well-established polyarthritis and gold therapy. It was accompanied by in-vitro evidence of suppressed cell-mediated immune responses and by development of serum antismooth muscle antibodies. These features are unusual and support theories that this disease has an immunological basis. Improvement occurred with prednisone and azathioprine therapy, suggesting that combined use of these agents is useful in some patients with AILD. The patient subsequently developed a lymphoma.     

Angioimmunoblastic lymphadenopathy and squamous cell carcinoma of lung

The development of angioimmunoblastic lymphadenopathy in a patient with a slowly growing squamous cell carcinoma of the lung is reported. The possible relation between the two concomitant conditions in this rare case is proposed.     

A study of lymphocyte subsets in patients with angioimmunoblastic lymphadenopathy

Immunological marker studies of peripheral blood lymphocytes in 22 patients with typical angioimmunoblastic lymphadenopathy were carried out. There was a decrease of the absolute lymphocyte number, of T-helper cells and the T4/T8 ratio in the active stage of the disease. The active T-cells and total T-cells were reduced both in the active and in the inactive state. The number of B-cells was in both states increased. Implications and possible mechanism of these observations are discussed. The histological findings and the clinical picture of angioimmunoblastic lymphadenopathy (AILD) or immunoblastic lymphadenopathy (IBL) were described by Frizzera et al (1974) and Lukes & Tindle (1975). The aetiology and pathogenesis of AILD are unknown. Hyperimmune phenomena, hypersensitivity (Lukes & Tindle, 1975), and chronic antigenic stimulation (Neiman et al, 1978) were suggested as possible factors. A defect in T-cell regulatory function with secondary B-cell system proliferation was also postulated due to the decreased T-suppressor cells (Lukes & Tindle, 1975; Frizzera et al, 1974). In almost all of the reported cases of AILD there has been a decrease in T-cells and an increase in B-cells (Pruzanski, 1980). In this report we describe the results of immunological studies of peripheral blood lymphocytes in 22 patients with typical AILD. We have found that the active state of the disease is characterized by T-lymphopenia due to the decrease of OKT4 positive cells.     

Rubella virus antigen in lymphocytes of patients with angioimmunoblastic lymphadenopathy (AIL)

Summary Lymph node sections from 14 patients with angioimmunoblastic lymphadenopathy (AIL) were incubated with fluorescein-labeled specific antiserum against rubella virus antigen. In lymphoid cells from 11 patients intracytoplasmic rubella antigen was demonstrated. The results support the idea of a persistent virus infection in AIL.The investigations were supported by grant Kr 476/4 of the German Science FoundationWe thank Miss Hannelore Weisheit for expert technical help     

Angioimmunoblastic lymphadenopathy with dysproteinemia. A pathogenetic link between lymphoid proliferation and malignant lymphoma.

Two patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) were studied. Both patients had marked increases in all three major immunoglobulin classes, and both lacked suppressor cell activity in vitro. These findings are consistent with the theory that AILD is a defectively regulated immune response to an unidentified antigen(s) and could provide clues to the pathogenesis of other lymphoproliferative disorders as well.     

Bone marrow biopsy findings in angioimmunoblastic lymphadenopathy

Bone marrow biopsies from 13 cases of lymph-node-biopsy-proven angioimmunoblastic lymphadenopathy (AILD) were studied. Eight cases (62%) showed a characteristic 'granulomatoid' lymphoreticular infiltrate composed of a mixture of lymphocytes, epithelioid histiocytes, immunoblasts, plasma cells and eosinophils in varying proportions. Proliferation of blood vessels, although much less prominent than that described in lymph nodes, and a marked degree of reticulin fibrosis were also noted. The pattern of involvement was mainly focal and rarely diffuse. The foci were either single or multiple, and were distributed throughout the marrow but were only rarely paratrabecular. The associated haematopoietic marrow findings were nonspecific regardless of degree of bone marrow involvement. The histopathology of involved bone marrows in angioimmunoblastic lymphadenopathy is such that in some cases it should strongly suggest the diagnosis even in the absence of a prior definitive lymph node biopsy. Differentiating features from other disorders that might be confused with AILD are discussed. Survival rate was adversely affected by bone marrow involvement.     

Angioimmunoblastic lymphadenopathy presenting as superior vena caval obstruction

A 60-year-old man presented with features of superior vena cava (SVC) obstruction. On evaluation, he was diagnosed as having angioimmunoblastic lymphadenopathy with dysproteinemia (AILD). SVC obstruction due to AILD, to our knowledge, has not been described.     

Angioimmunoblastic lymphadenopathy with hypogammaglobulinemia. Possible role of monocyte suppression

A patient wit angioimmunoblastic lymphadenopathy had low serum immunoglobulin values and no antibodies to injected immunogens. This occurred despite the proliferation of polyclonal B cells. T cells were deficient in number and in lymphoproliferative responses, but their helper and suppressor functions were maintained. Ia-antigen bearing leukocytes from the patient stimulated poorly in mixed leukocyte culture. In vitro immunoglobulin synthesis by mononuclear leukocytes form the patient was severely impaired. These leukocytes actively suppressed immunoglobulin synthesis by normal cells from healthy subjects in co-culture. The responsible cell had characteristics of a monocyte. The suppression was selective for humoral immunity and was manifest despite normal numbers of monocytes. It appears that heterogeneous immunoregulatory abnormalities can underlie the syndrome of angioimmunoblastic lymphadenopathy. Furthermore, monocyte suppressor abnormalities may be implicated in clinical disease phenomena.     

Levamisole and autoimmunity in angioimmunoblastic lymphadenopathy.

A case of angioimmunoblastic lymphadenopathy (AILD) with important autoimmune symptoms disappearing under Levamisole therapy is reported. Since Levamisole is thought to have no direct effect on B cells, it is supposed that in AILD it regulates B lymphocyte activity via the restoration of impaired T cell functions.     

Arthritis and angioimmunoblastic lymphadenopathy.

We report 2 contrasting cases of a seronegative polyarthritis associated with angioimmunoblastic lymphadenopathy (AILD). Both cases were nonerosive, with symmetrical involvement of the elbows, wrists, knees, and ankles. In one the arthritis appeared concurrently with the main systemic manifestations of AILD. The second presented with polyarthritis 18 months before the onset of AILD. This patient received azathioprine for 11 months before developing AILD, which raises the possibility of this drug being the causative agent.     

Angioimmunoblastic lymphadenopathy following Kaposi's sarcoma

The close relationship of Kaposi's sarcoma (KS) with other lymphoproliferative disorders is a poorly understood, but well documented, phenomenon. A case is presented of a 68-year-old woman with the classical form of cutaneous KS in whom disappearance of the lesions after treatment was shortly followed by the development of angioimmunoblastic lymphadenopathy, pursuing a fulminant course to death. Postmortem examination revealed diffuse involvement of the marrow, spleen, liver, and lymph nodes by the immunoblastic proliferation. The close association of these two conditions may represent more than a chance occurrence. The appearance of a constellation of nonspecific symptoms suggestive of a lymphoproliferative disorder in debilitated patients with KS should alert the physician to the possibility of the development of this rare complication.