狼疮性肾炎2

CASE REPORT R. Gupta Æ N. Gulati Æ A. Gupta Æ A. Kumar A. K. Dinda Æ S. K. Sharma Unusual presentation of lupus nephritis Received: 12 July 2003 / Accepted: 1 April 2004 / Published online: 13 October 2004 � Springer-Verlag 2004 Abstract We report a male patient who presented with pyrexia, generalized lymphadenopathy, hepatospleno- megaly, and pleural effusion with no cutaneous or musculoskeletal symptoms. Despite extensive investiga- tion, no cause was detected. His initial serology was also negative for autoantibodies. The patient was placed on a trial of antitubercular treatment in view of a positive Mantoux test. His disease evolved into the full clinical picture of systemic lupus erythematosus with nephritis (World Health Organisation class IV) and strongly positive antinuclear antibody and dsDNA over a period of months. He was treated successfully with intravenous cyclophosphamide pulses along with oral prednisolone, and the disease was still in remission after 3 years of follow-up. Keywords Lymphadenopathy Æ Nephritis Æ Systemic lupus erythematosus Introduction Pyrexia with generalized lymphadenopathy is a very common problem in clinical practice. There are many causes of this presentation—tuberculosis, sarcoidosis, lymphomas, human immunodeficiency virus, infectious mononucleosis, connective tissue diseases, etc. Although lymphadenopathy is a common feature of systemic lupus erythematosus (SLE), it is rarely the primary presenting feature. In 1943, Fox and Roshan [1] reviewed 277 SLE patients in the literature and concluded that lymph node enlargement occurred in 67%. The most common sites were cervical (43%), mesenteric (21%), axillary (18%), and inguinal (17%). Unusual sites such as hilar, medi- astinal, and retroperitoneal were reported, as in the present case. We report an unusual case presenting with fever, generalized lymphadenopathy, and antinuclear antibody (ANA) seronegativity and later developing full-blown SLE with nephritis. Case report A previously healthy, 35-year-old male was referred to our hospital with moderate-grade, intermittent fever, and weight loss of 10 kg over the previous 3 months. There was no history of skin rash, photosensitivity, arthritis, oral ulcer, alopecia, urinary, or bowel com- plaints. On examination, the patient was emaciated and febrile (39�C), and his pulse rate was 110/min, blood pressure 130/80 mmHg, and respiratory rate 22/min. He had multiple, 1-cm, nontender, and firm lymph nodes in the cervical and axillary regions. Systemic examination revealed left pleural effusion and hepatosplenomegaly. Initial laboratory data revealed hemoglobin 9.7 g/dl, total leukocyte count (TLC) 9,800/mm3 with normal differential count, platelet count 150,000/mm3, and erythrocyte sedimentation rate 118 mm in the 1st h (Westergren method). Urinalysis, electrolytes, coagula- tion profile, and kidney and liver function tests were normal. Blood and urine cultures were sterile. Chest X- ray revealed left hilar lymphadenopathy and pleural effusion. Antinuclear antibody was negative by immu- nofluorescence technique, and anti-dsDNA antibody was within normal limits by enzyme-linked immuno- sorbent assay. The Mantoux test revealed 12-mm indu- ration. Cervical lymph node biopsy showed reactive follicular hyperplasia. The pleural fluid was exudative, with lymphocyte predominance. Examination revealed cellular bone marrow without any granuloma, and R. Gupta (&) Æ N. Gulati Æ A. Gupta Æ A. Kumar Æ S. K. Sharma Clinical Immunology and Rheumatology Services, Department of Medicine, All India Institute of Medical Sciences, Ansari Nagar, 110029 New Delhi , India E-mail: guptarajiva@hotmail.com Tel.: +91-11-26594838 Fax: +91-11-26862663 A. K. Dinda Department of Pathology, All India Institute of Medical Sciences, New Delhi, India Rheumatol Int (2005) 25: 130–132 DOI 10.1007/s00296-004-0478-5 staining for acid-fast bacilli and fungus was negative. Liver biopsy was normal. We considered disseminated tuberculosis as the probable diagnosis, and empirical antitubercular therapy was started (isoniazid, rifampi- cin, pyrazinamide, ethambutol). The patient did not show improvement with 6 weeks of antitubercular therapy. His fever persisted and he continued to lose weight. Further investigation with re- peat axillary lymph node and bone biopsies did not contribute to the diagnosis. Contrast-enhancing com- puted tomography (CECT) scan of the chest revealed mediastinal lymphadenopathy and left pleural effusion. Minimal ascites and multiple retroperitoneal lymph nodes were revealed by CECT of the abdomen. During the hospital stay, he developed pancytopenia (hemo- globin 5.2 g/dl, TLC 2,900/mm3 with normal differential counts, and platelet count 68,000/mm3). A direct Coo- mbs’ test was positive. The patient’s immunologic profile was repeated. It showed strongly positive ANA (homogenous pattern) in a titer of 1:320, anti-dsDNA antibody was negative at 10 IU/dl (normal 0–30), and the C3 level was low, at 28 mg/dl (normal 60–120 mg/dl). Antineutrophil cyto- plasmic autoantibody and rheumatoid factor tests were negative. Differential diagnosis of drug-induced SLE or low-grade lymphoma with autoimmune hemolytic ane- mia was considered. In view of autoimmune hemolytic anemia, oral prednisolone (1 mg/kg) was started and antitubercular drugs were stopped. The patient re- sponded well, became asymptomatic on the 10th day of therapy, and was discharged from hospital. During the follow-up after 1 month, his blood pres- sure was 170/110 mmHg and urinalysis showed active sediment (red blood cells 20–25/high-power field) and proteinuria (3+). Twenty-four-hour urinary protein was 2.1 g. Kidney biopsy showed diffuse proliferative glo- merulonephritis (World Health Organisation class IV) (Fig. 1, Fig. 2). Repeat immunologic profile revealed ANA strongly positive with a titer of >1:320 (homog- enous pattern), anti-dsDNA positive at 110 IU/dl, and low C3 at 38 mg/dl. The patient was started on monthly intravenous cyclophosphamide pulse (15 mg/kg) for 6 months, followed by pulse therapy every 3 months. Steroid was gradually tapered off over 6 months. After 3 years of therapy, the patient is completely asymp- tomatic, with normal urine examination. Discussion In this report, we describe a male patient with SLE who presented initially with pyrexia, generalized lymphade- nopathy, hepatosplenomegaly, and pleural effusion. Initial differential diagnosis of a chronic infectious or lymphoproliferative disorder was considered, especially in view of the negative ANA; but we found no evidence of an infection or lymphoproliferative disorders, despite extensive investigation including repeated blood and urine cultures and various radiologic investigations. The patient also had a number of tissue biopsies including lymph node, bone marrow, and liver. He had a positive Mantoux test, so antitubercular therapy was started empirically but with no improvement in symptoms. Subsequently, this patient’s lupus evolved with man- ifestations of direct Coombs’-positive hemolytic anemia, pancytopenia, and serositis along with strongly positive ANA and low C3 levels but normal anti-dsDNA. We were still not sure about the diagnosis of SLE, as the ANA seroconversion may have been due to isoniazid given as part of the empirical antitubercular therapy. Seroconversion occurs in about 20–22% of patients taking isoniazid [2, 3], but only a few (less than 1%) develop clinical SLE [4]. Our patient was unlikely to have had drug-induced SLE, as his disease progressed to diffuse proliferative glomerulonephritis with positive ANA, dsDNA, and hypocomplementemia, despite Fig. 1 Photomicrography of kidney biopsy showing diffuse endo- capillary cell proliferation, neutrophil infiltration, fibrin deposition, and focal tuft necrosis (H&E, ·400) Fig. 2 Immunofluorescence shows granular capillary wall deposits of IgG in the glomerulus (FITC, ·800) 131 taking high doses of oral steroids and stopping antitu- bercular drugs (including isoniazid), although other symptoms improved remarkably. One similar case was reported in a 13-year-old female presenting with gener- alized lymphadenopathy and who also developed renal involvement despite steroid therapy, but she had positive ANA and positive antibodies to dsDNA [5]. Lymphadenopathy is a rare primary presenting fea- ture of SLE. Dubois et al. [6] reviewed 520 cases of SLE and found lymphadenopathy in 59%. Cervical lymph nodes were enlarged in 24% of cases. Cervical lymph- adenopathy as the presenting feature was present in 2% of the cases, and generalized lymphadenopathy was the presenting feature in 1% of cases. This finding was corroborated in other studies as well [1, 7, 8]. Lymph nodes in lupus are usually nontender, dis- crete, and 3–4 cm in size. They can be large enough to raise the suspicion of lymphoma. In some patients, there may be fluctuations in lymphadenopathy with disease exacerbations. Histology usually reveals diffuse reactive hyperplasia, as in our case. It is associated with varying degrees of coagulative necrosis. Three patterns of fol- licular hyperplasia have been described: those resem- bling Castleman’s disease, T-zone dysplasia with hyperplastic follicles, and nonspecific follicular hyper- plasia. Hematoxylin bodies, which are aggregates of DNA, immunoglobulin, and polysaccharide, are pathognomic of lupus but not frequently seen [1, 8, 9]. Besides lymphoma and chronic infection, two other disease processes—Castleman’s disease and Kikuchi’s disease—were also considered in the differential diag- nosis. The former is a rare lymphoproliferative disorder of young adults characterized by lymphadenopathy and which mimics malignant lymphoma. Its most common sites are the neck and anterior mediastinum. Three his- tologic variants (hyaline vascular, plasma cell, and mixed) as well as two clinical variants (localized and multicentric) have been described. The hyaline vascular variant, which represents 90% of cases, is usually asymptomatic. The plasma cell variant presents with fever, anemia, lymphadenopathy, organomegaly, and hypergammaglobulinemia. The multicentric type resembles lupus, with persistent lymphadenopathy despite steroids [10]. Kikuchi’s disease, or subacute histiocytic necrotizing lymphadenitis, is a self-resolving disease of young wo- men characterized by cervical adenopathy, fever, upper respiratory symptoms, weight loss, and leukopenia in 50% of cases. Extranodal involvement is rare and affects the bone marrow, skin, and myocardium. This disease is believed to be an autoimmune disorder, and patients are at risk of developing SLE. The CT and MRI appear- ances are variable. It may mimic lymphoma, and asso- ciated nodal necrosis may raise the suspicion of metastasis and tuberculosis. Many small, clustered, enhancing lymph nodes may be seen. The presence of plasma cells, hematoxylin bodies, and DNA in vessel walls in lymph node biopsy favors the diagnosis of SLE [11]. To conclude, we feel that in patients with fever and lymphadenopathy, even if ANA-negative at presenta- tion and having no evidence of infectious or neoplastic disease, SLE should be considered in differential diag- nosis, as the systemic manifestations of lupus can pre- cede, follow, or occur simultaneously with lymphadenitis. References 1. Fox RA, Rosahn PD (1943) The lymph node in disseminated lupus erythematosus. Am J Pathol 19:73–99 2. Rothfield NF, Bierer WF, Garfield JW (1978) Isoniazid induction of anti-nuclear antibodies: a prospective study. Ann Intern Med 88:650–652 3. Dhand R, Gilhotra R, Sehgel S, Malik SK (1987) Incidence of isoniazid-induced anti-nuclear antibodies in patients of tuber- culosis. Indian J Med Res 85:503–507 4. Salazae-Parmo M, Rubin RL, Garcia T (1992) Isoniazid in- duced systemic lupus erythematosus. Ann Rheum Dis 51:1085– 1087 5. Biner B, Acunas B, Karasalihoglu S, Vatansever U (2001) Systemic lupus erythematosus presenting with generalized lymphadenopathy: a case report. Turk J Pediatr 43:94–96 6. Dubois EL, Tuffanelli DL (1964) Clinical manifestation of systemic lupus erythematosus: computer analysis of 520 cases. JAMA 190:104–111 7. Cervera R, Khamashta MA, Font J et al (1993) Systemic lupus erythematosus: clinical and immunologic pattern of disease expression in a cohort of 1,000 patients. Medicine 72:113–124 8. Kassan SS, Moss ML, Reddick RL (1976) Progressive hilar and mediastinal lymphadenopathy in systemic lupus erythematosus on corticosteroid therapy. N Engl J Med 294:1382–1383 9. Kojima M, Nakamura S, Morishta Y (2000) Reactive follicular hyperplasia in the lymph node lesions from systemic lupus erythematosus patients—a clinicopathological and immuno- histological study of 21 cases. Pathol Int 50:30–42 10. 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