Hodgkin s Disease Presenting as Relapsing Polychondritis

Transcription

1 Hodgkin s Disease Presenting as Relapsing Polychondritis A Previously Undescribed Association Stephen B. Miller, Charles J. Donlan and Steven B. Roth Relapsing polychondritis is a rare syndrome thought to be autoimmune in nature and characterized by inflammation and degeneration of cartilage. The association with a reticuloendothelial malignancy has not previously been reported. A 46-year-old man presented typical clinical manifestations of relapsing polychondritis requiring 30 mg of prednisone daily for suppression. However within 6 months he developed chronic fatigue, fevers, night sweats, adenopathy, and splenomegaly leading to the diagnosis of Hodgkin s disease. Relapsing polychondritis is a rare syndrome characterized by inflammation and degeneration of cartilage, specifically ear and nasal cartilage, and often associated with ocular and cardiac involvement (1-3). Anemia, elevated sedimentation rate, and hypergammaglobulinemia are prominent laboratory features. The etiology of this disease is unknown hut the prevalent speculation is that it is autoimmune in nature. A number of concomitant disorders have been found in patients with relapsing polychondritis. These include rheumatoid ar- From the Department of Medicine, Naval Hospital, Portsmouth, Virginia Presented at the Virginia Regional American College of Physicians Meeting, Williamsburg, Virginia, March 17, The opinions or assertions contained herein are those of the authors and are not to be construed as official or reflecting the views of the Navy Department or of the Naval Service at large. LIEUTEANT COMMANDER STEPHEN B MILLER, MC USNR: Chief, Rheumatology Section; LIEUTENANT COM- MANDER CHARLES J DONUN, JR, Mc, UsN: Resident; LIEUTENANT COMMANDER STEPHEN B MILLER, MC, USNR: Staff Physician. Address reprint requests to: Dr Stephen B Miller, 38 Grove Street, Ridgefield, Connecticut Submitted for publication May 8, 1973; accepted December 13, thritis, Sjogren s syndrome, pregnancy, tuberculosis, myxedema, systemic lupus erythematous, rheumatic myocarditis, scleroderma, psoriasis, syphilis, diabetes insipidus, diabetes mellitus, renal tubular acidosis, herpes zoster, herpes simplex, and exophthalamus (1). An association with malignancy has been suggested with 2 cases in in patients who were later diagnosed as having carcinoma of the pancreas and prostate (4). The association with a reticuloendothelial malignancy has not been reported previously. We present a case of a man who developed typical clinical manifestations of relapsing polychondritis sup pressed, as expected, by corticosteroid therapy. However his clinical course changed with the development within 6 months of peripheral adenopathy and splenomegaly, leading to the diagnosis of Hodgkin s disease. CASE REPORT Patient JB, a 46-year-old Caucasian male was in excellent health until the fall of 1971 when he began to experience episodic tenderness, swelling, and redness of both ears. These manifestations became persistent but were never associated with 598 Arthritis and Rheumatism, Vol. 17, No. 5 (September-October 1974)

2 HODGKIN S DISEASE Fig 1. Section of external ear cartilage showing destruction of cartilage and proliferation of adjacent connective tissue (H & E stain, 400X). nasal or tracheobronchial symptoms. All laboratory tests were unremarkable with the exception of a persistently elevated sedimentation rate, in the mm/hr range by the Wintrobe method. Trials with salicylates and indomethacin were unsuccessful in suppressing the external ear inflammation, and prednisone, in doses up to 30 mg per day, was required. The working diagnosis was relapsing polychondritis. The patient s condition stabilized but frequent attempts to lower the pretlnisone dose led to exacerbation of symptoms. In the spring of 1972 he noted increasing fatigue associated with evening fevers to 102 F and drenching night sweats. He was then admitted to the hospital for a complete reevaluation. Physical examination was unremarkable; specifically, there was no acute inflammation of the ears, nor were any ocular, joint, or cardiac abnormalities noted. Laboratory studies revealed a hematocrit of 34%, a white blood cell count of 6200, and a sedimentation rate of 45 mm/hr. Peripheral blood smear showed normocytic, normochronic red cells with marked rouleaux formation. Total protein was 9.3 g/loo ml with an albumin of 1.9 gyo and a gamma globulin of 3.9 g/100 ml. There was no gamma spike. The alkaline phosphatase was elevated to 90 IU units (normal 11-36). An exten- sive laboratory investigation was unrevealing, and included normal serum electrolytes, BUN, creatinine, calcium, phosphorous, CPK, and transaminases. Latex fixation and LE preps were negative. Chest X-ray, UGI series and barium enema were normal, and fungal serologies and an intermediate PPD skin test were negative. A liver scan and biopsy were unremarkable as was a bone narrow examination. Cultures of the blood, liver, and bone marrow were negative. Biopsy of external ear cartilage showed changes coilsisterit with relapsing polychondritis. There was loss of basophilic staining of the cartilaginous matrix with invasion of proliferating connective tissue (Figure 1). The hospital course was characterized by a slowly declining hematocrit to 250/,, chronic fatigue, and daily fevers to 104 F. The alkaline phosphdtase continued elevated with mild transaminase elevation. Prednisone was increased to a maximal dose of 100 mg per day with moderate improvement in his symptoms. The fever subsided, his strength increased, and the sedimentation rate and alkaline phosphatase levels declined, although not to normal. This improvement was short-lived however, and he was readmitted for another evaluation. His physical examination was essentially unchanged except for a cushinoid appearance: Labo- Arthritis and Rheumatism, Vol. 17, No. 5 (September-October 1974) 599

3 MILLER ET AL Fig 2. Section of spleen revealing Reed-Sternberg cell (H & E, 400X). ratory studies revealed the alkaline phosphatase again elevated to its previous levels, a leukocytosis in the 15,000-30,000 range and elevated blood sugars which were felt to be steroid-induced. Bone marrow biopsy and radiologic metastatic bone survey were unrevealing and a repeat liver biopsy showed only mild fatty change. High fevers, night sweats, and marked anemia continued. There was no evidence of hemolysis. Due to continued refractoriness to high dose prednisone a trial of gradually increasing methotrexate (amethopterin) was begun. The prednisone was tapered to 20 mg per day concomitant with the methotrexate administration. No clinical improvement occurred and the methotrexate was discontinued. Subsequently new physical findings of a palpable axillary node and splenomegaly were noted. Biopsy of the node revealed Hodgkin s disease of the mixed cell type. Staging laparotomy revealed Hodgkin s involvement in the spleen (Figure 2) with negative liver and para-aortic nodes. The patient was then begun on cyclic chemotherapy, using nitrogen mustard, vincristine, procarbazinc, and prednisone. His clinical course deteriorated steadily however, and he died of staphylococcal pneumonia after completing two courses of MOPP therapy. DISCUSSION The patient, as he originally presented, demonstrated clinical and laboratory manifestations which supported the diagnosis of relapsing polychondritis, ie, ear cartilage inflammation, fever, hypergammaglobulinemia, anemia, elevated sedimentation rates, and cartilaginous histologic confirmation. He did not have cardiac, ocular, or joint involvement. Initially his response to relatively low dose steroids was adequate and consistent with the usual response in previously reported cases of relapsing polychondritis. Subsequently however, the illness changed character with the development of marked systemic symptoms. High fevers, night sweats, weakness, and weight loss were prominent features. In addition the liver function abnormalities and persistent anemia were more severe than previously recorded in the literature. It was these atypical features and the inability to 600 Arthritis and Rheumatism, Vol. 17, No. 5 (September-October 1974)

4 HODGKIN S DISEASE suppress disease activity with even high dose steroids that led to an extensive search for another illness. Initial ear cartilage biopsy during a period of active inflammation failed to reveal any cartilage despite sampling from usually cartilaginous areas. The same situation occurred in case 2 of Dolan s review (1). In both their case and ours however, characteristic cartilaginous findings were obtained during the quiescent period. Prior to the emergence of the diagnosis of Hodgkin s disease our attempts to suppress the systemic manifestations of the polychondritis with an immunosuppressive agent ie, methotrexate, were unsuccessful. A number of authors (1,2) have speculated that relapsing polychondritis has an autoimmune etiology. Herman and Dennis specifically studied this problem. In a study entitled Zmmunopathologic Studies in Relapsing Polychondritis (5), their findings suggested a role for cellular immune mechanisms in the disease. As noted earlier there has been only one reference in the literature to relapsing polychondritis preceding the emergence of a neoplasm (4). In this report of two cases, only one is accompanied by histologic documentation of cartilage involvement. In this case an SO-year-old man was found to have carcinoma of the pancreas discovered 4 months after presenting with ear cartilage inflammation, elevated sedimentation rates, and hypergammaglobulinemia. hiiller (6) reported 17 patients who presented evidence of both malignant and immune disease. The disease associated with the malignant lymphomas ranged from diffuse connective tissue disease such as rheumatoid arthritis and systemic lupus erythematosus to the nephrotic syndrome and ataxia telangiectasis. They were referred to as immune diseases in the sense that they have a possible immunological etiology or an associated immune disturbance. Five of the 17 patients had Hodgkin s disease. Two patients experienced the simultaneous appearance of Hodgkin s disease with another disease, namely dermatomyositis in one and the nephrotic syndrome in the other. Two additional patients showed dissimultaneous appearance of Hodgkin s disease with another disease, namely lupus erythematosus and discoid lupus erythematosus. The fifth case was originally diagnosed as Hodgkin s disease, but after 4 years of clinical observation, the most compatible diagnosis was systemic lupus erythematosus. Hench et a1 (7) found 22 examples of diffuse connective tissue disease in 1000 patients with lymphoma and malignancies (22y0). Lea (8) found a 6.5y0 presence of both malignant lymphoproliferative disease and rheumatoid arthritis compared to a control population of 1.5y0. Two studies of the prevalence of rheumatoid arthritis and systemic lupus erythematosus in the general population (9,lO) give a combined prevalence of these disorders of only O.41y0. We can only speculate whether the occurrence of relapsing polychondritis with Hodgkin s disease represents another example of the association of immune disease with lymphoproliferative disorders. ACKNOWLEDGMENT The authors wish to thank the staff pathologists of the Naval Hospital, Portsmouth, Virginia for their assistance. REFERENCES 1. Dolan DG, Lemmon GB, Teitelbaum: Relapsing polychondritis. Am J Med 41 : , Hollander JE, McCarty DJ: Arthritis and Allied Conditions. Philadelphia, Lea and Febiger, 1972 Arthritis and Rheumatism, Vol. 17, No. 5 (September-October 1974) 601

5 MILLER El AL 3. Pearsori CM, Kline HM, Newcomer VD: Relapsing polychondritis. New Engl J Med 263: 51-58, Odkuist L: Relapsing polychondritis. Acta Otolaryngo 70: , Herman JH, Dennis MV: Immunopathologic studies in relapsing polychondritis. J Clin Invest 52:549, Miller DG: The association of immune disease and malignant lymphoma. Ann Intern Med 66: , Hench PK, Mayne JG, Kiely JM, et al: Clinical study of the rheumatic manifesta- tions of lymphoma. Arthritis Rheum 5:301, 1962 (abstr) 8. Lea AJ: An association between the rheumatic diseases and the reticuloses. Ann Rheum Dis 23:480, Mikkelson WM, Dodge DJ, Duff I, et al: Clinical and serological estimates of the prevalence of rheumatoid arthritis in the population of Tecumseh, Michigan. Arthritis Rheum 5:117, 1962 (abstr) 10. Siege1 M, Seelenfreund M: Racial and social factors in systemic lupus erythematosus. JAMA 191:77, Arthritis and Rheumatism, Vol. 17, No. 5 (September-October 1974)