Introduction

Lymphadenopathy is a relatively common manifestation of connective tissue diseases (CTD), particularly rheumatoid arthritis [1-4], and systemic lupus erythematosus (SLE) [4-7]. The clinically palpable nodes are predominantly located in the axillary and cervical areas and are usually non tender and discrete, varying in size from a few millimeters to 3-4 centimeters. However, massive abdominal/retroperitoneal lymphadenopathy, as a manifestation of the disease itself, is extremely rare and very few cases have been described so far [8,9]. When such a massive lymphadenopathy, especially in the abdomen, is encountered in a CTD patient, the physician’s main concern is to rule out infectious causes [10-16], granulomatous diseases [17], but also malignant, and rarely benign [18-22], lymphoproliferative disorders. We present herein two patients with CTD, one with SLE and the other with mixed connective tissue disease (MCTD), in whom massive abdominal lymphadenopathy was directly related to activity of the underlying disease and not to another cause. The purpose of this presentation, besides reporting a very rare manifestation of CTD activity, is the sensitization of the physician to this rare occurrence which should be included in the differential diagnosis of similar cases, without of course underestimating the importance of prompt and appropriate study to rule out other more serious possibilities.

1^st Case: A 48 year old caucasian male was diagnosed with SLE 15 years ago, when he presented with fever, serositis, autoimmune hemolytic anemia and flushing, and positive ANA (1/640 homogeneous), anti-dsDNA, and anticardiolipin antibodies. During follow up, he had experienced two recurrences of his disease with low grade fever and serositis, treated by the addition of small doses of steroids to his regular hydroxychloroquine treatment. Moderate interstitial lung disease had also been detected and he had been regularly followed with pulmonary function testing and HRCT. In May 2010, after an asymptomatic period of 6 years, he presented with fatigue, fever up to 380C, abdominal pain and nausea. An abdominal CT (Figure 1A and 1B) was reported as showing markedly enlarged and sharply delineated retroperitoneal lymph nodes along the abdominal aorta and the iliac arteries. Inguinal lymph nodes (up to 2.5 cm) were also detected, along with a small pleural effusion. No other significant pathology of the abdominal viscera was present, except for a slightly swollen spleen. HRCT confirmed the presence of enlarged axillary lymph nodes, which had been clinically palpated, and showed minor fibrotic lesions in the lung parenchyma. Upper and lower gastrointestinal endoscopy revealed no abnormality. Serologic profile included positive ANA at a 1:1280 titer and of homogeneous pattern, positive anti-dsDNA 300 units (normal up to 15 units) and low C3 60 mg% and C4 10 mg% complement levels (normal 79-152 mg% and 16-38 mg% respectively). Hematology showed a mild anemia with normal reticulocyte count, lymphopenia (900 cells/mm³) and mild thrombocytopenia (115000/mm³), whereas ESR was 60 mm in the first hour. During hospitalization no focus of infection was found, whereas a meticulous search for viral infection was negative. Serum angiotensin converting enzyme (SACE) level was normal. An axillary lymph node biopsy did not reveal any specific pathology and the histologic picture was consistent with reactive lymphadenitis. In order to further exclude any infectious, lymphoproliferative or metastatic disease, the patient underwentlaparoscopic biopsy of a lymph node block (Figure 2). Both lymph node biopsies (axillary and abdominal) displayed similar histological findings. In more detail, the abdominal lymph node architecture was preserved, although there was an expansion of the interfollicular zone with prominent postcapillary venules. The follicles were small or regressed with only few large secondary follicles with germinal centers present. No granulomas or metastatic epithelial elements were observed. The immunohistochemical evaluation confirmed the reactive nature of the follicles which were CD20 and CD79A positive, with CD10/bcl-6 positive and bcl-2 negative germinal center cells, and a network of CD23 positive dendritic cells. The expansion of the T-cell interfollicular zone was underlined by the expression of all T-cell markers (CD3, CD5, CD2, CD7), with predominance of CD4 T-cells and the presence of scattered CD30 positive immunoblasts. In this zone, there was neither CD23 and CD10 expression to suggest an angioimmunoblastic T-cell lymphoma, nor presence of CD15 positive cells or Reed-Sternberg/Hodgkin-like cells. The diagnsosis was reactive lymphadenitis of interfollicular type, without any findings compatible with lymphoproliferative, metastatic malignant or granulomatous disease. Appropriate stains and cultures did not reveal any infectious agent. Based on the above, an underlying disease exacerbation was diagnosed and the patient was treated with prednisolone (20 mg/day) with gradual dose reduction. Two days later, the patient’s condition significantly improved with disappearance of his fever and fatigue, whereas laboratory values began to normalize. Five months after discharge and off steroids, he was in good condition, without symptoms and with normal laboratory tests except for positive ANA and slightly low complement. The size of lymph nodes was reduced in a repeat abdominal CT. Since then and up to now, the patient has remained in good health on hydroxychloroquine 200mg daily. 

     

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