in the cerebrospinal fluid and a resistant strain in the blood. The clinical course of these three patients follows. Patient 1 A 2-month-old boy was admitted to hospital with a clinical diagnosis of moderate bronchiolitis. Twelve hours after admission a spiking fever developed without localizing signs. A blood sample was drawn for culture and he was given ampicillin intravenously, 100 mg/kg daily. Because the fever persisted a second blood sample was drawn 3 days later and the ampicillin dose was increased to 200 mg/kg daily. The fever then subsided quickly and the patient had an uneventful recovery. The first blood culture grew both ampicillin-sensitive and ampicillin-resistant colonies of H. influenzae type b (by disc diffusion and /3-lactamase tests), and the second grew only the resistant strain. Patient 2 A 21-month-old girl was admitted to hospital with a febrile convulsion and bilateral otitis media. Results of analysis of the cerebrospinal fluid were normal. The patient did well taking orally administered amoxicillin, 50 mg/kg daily. A blood sample drawn on the day of admission yielded on culture both ampicillin-sensitive and ampicillin-resistant strains of H. influenzae type b. Patient 3 A 10-month-old boy was admitted to hospital with purulent meningitis. His illness had begun 24 hours earlier with fever, chills, vomiting and apathy. He had previously had three episodes of focal convulsions involving the right arm. A spinal tap revealed purulent cerebrospinal fluid; the leukocyte count was 3.2 x 10./l and the cells were all neutrophils. The glucose concentration was 29 mg/dl and the protein content was 192 mg/dl. Culture of the cerebrospinal fluid grew H. influenzae type b sensitive to ampicillin. A blood sample drawn at the time of admission yielded on culture an ampicillinresistant strain of the same organism. The patient was initially treated with intravenous administration of ampicillin, 300 mg/kg daily, and

chioramphenicol, 100 mg/kg daily; References chioramphenicol alone was given 1. SYRIoPouLou V, SCHEIFELE D, SMITH once the results of the blood culAL, et al: Increasing incidence of ture became known. The patient ampicillin resistance in Hemophilus influenzae. J Pediatr 92: 889, 1978 made a good recovery. 2. SCHWARTZ R, RODRIGUEZ W, KHAN Discussion W, et al: The increasing incidence of ampicillin-resistant Haemophilus inDelage and associates5 reported tluenzae. JAMA 239: 320, 1978 the recurrence of H. influenzae 3. THORNSBERRY C, GAVAN TL, GERtype b meningitis and septicemia LACK EH, et al: New Developments in Antimicrobial Agent Susceptibility after apparently successful treatTesting, Cumitech ser 6, American ment; the initial strains had been Society for Microbiology, Washingampicillin-sensitive but the new ton, DC, 1977. strains were ampicillin-resistant. In 4. CATLIN BW: lodometric detection of an accompanying article Albritton Haemophilus injluenzae beta-lactamase: rapid presumptive test for amand colleagues6 reported a case of picillin resistance. Antimicrob Agents subdural empyema due to ampicil7: 265, 1975 lin-resistant H. in!luenzae type b 5. Chemother DELAGE 0, DECLERCK Y, LESCOP J, occurring after ampicillin treatment et al: Hemophilus in/luenzae type b of meningitis due to an ampicillininfections: recurrent disease due to ampicillin-resistant strains. J Pediatr sensitive strain of the same organ90: 319, 1977 ism. Mixed infection at the time of 6. ALBRITTON WL, HAMMOND G, HOBAN onset of illness was postulated as 5, et al: Ampicillin-resistant H. inthe cause of the emergence of amfluenzae subdural empyema following picillin-resistant strains in both successful treatment of apparently ampicillin-sensitive H. influenzae mencases, but evidence for this was ingitis. Ibid, p 320 found in only the former.5 Our three cases illustrate well that mixed infections do exist in HLA-B8, autoimmune children with primary bacteremia polyendocrinopathy and systemic due to the classic pyogenic organ- lupus erythematosus isms, and add strength to the hypo- To the editor: A major feature of thesis that mixed infections at the systemic lupus erythematosus is the time of onset of illness are the chief formation of antibodies to various cause of antibiotic resistance in H. autoantigens such as nuclear comin!luenzae type b infections during ponents. However, the formation of ampicillin therapy. antibodies against endocrine orIn addition, these data provide gans is unusual.1 The genetic preevidence for the increased circula- disposition to the development of tion of ampicillin-resistant strains systemic lupus erythematosus has of H. influenzae in the Montreal re- been determined from family gion. Therefore, therapy for severe studies and studies of histocompadisease possibly or definitely due tibility antigens.' to H. in!luenzae type b should inJuvenile diabetes mellitus has reclude the administration of a drug cently been ascribed to the formaeffective against ampicillin-resistant tion of autoantibodies against panstrains, especially when the men- creatic islet cells; these antibodies inges are involved. Finally, the fact are detectable in most patients at that the presence of resistant strains the onset of the disease.3 The forin the blood of patients 1 and 2 mation of autoantibodies to other was detected only by the growth of endocrine organs has also been decolonies in the zone of inhibition tected in patients with diabetes melin the disc diffusion test supports litus as part of a polyendocrinopathe recent recommendation not to thy.4" We describe a patient in rely solely on the f3-lactamase test whom, 2 years after presentation to determine the susceptibility of with juvenile diabetes mellitus, sysH. in!luenzae type b to ampicillin.' temic lupus erythematosus was GILLES DELAGE, MD diagnosed. CHRISTIANE GAUDREAU, MD Infectious diseases service Case report Departments of microbiology A 6-year-old girl presented with and immunology, and of pediatrics diagnostic features of juvenile diaH6pital Sainte-Justine University of Montreal betes mellitus and was treated with Montreal, PQ insulin. She had complement-fixing

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antibody titres of 1/80 against thyroglobulin and thyroid microsomal antigen, and 1/320 against adrenal antigen. Investigation of thyroid status indicated hypothyroidism and she was treated with levothyroxine. Two years later she presented with a maculopapular eruption on her face and polyarthritis of 2 months' duration. A diagnosis of systemic lupus erythematosus was made on the basis of an antinuclear antibody titre of 1 / 1240 and positive lupus erythematosus cell preparations. The serum concentration of the C3 component of complement was 46 mg/dl (normal 80 to 160 mg/dl). Biopsy of skin and kidney showed immunoglobulin deposition. She was initially treated with prednisone 30 mg/d and the dose was later decreased to 30 mg every other day with satisfactory control of the systemic lupus erythematosus. This necessitated alterations to the dose of insulin. The patient later had two episodes of acute nephritis. The first episode responded to vigorous therapy with prednisone and azathioprine. At the time of admission her diabetes was out of control; the blood glucose concentration was between 300 and 600 mg/dl and the serum creatinine concentration was 292 p.mol/l (3.3 mg/dl). Associated proteinuria (3 g of protein was excreted every 24 hours) and nephritic urinary sediment were noted. She was treated with cyclophosphamide, azathioprine and prednisone. However, after an initial decrease in the serum creatinine concentration, renal function deteriorated and she died 3 weeks after admission to hospital. During the course of the disease histocompatibility antigen testing of lymphocytes revealed HLA antigens A2, Aw24, B8 and B27. Discu.ssion A genetic predisposition to systemic lupus erythematosus has been suggested by HLA tissue-typing studies. HLA-B8 and -Bwl 5 are observed more frequently in patients with this disease than in control subjectsY Similarly, results of studies on patients with diabetes mellitus of juvenile onset have indicated an increased frequency of

the disease in patients with HLAB8, thus providing evidence of a genetic predisposition for the development of the disease.3 Up to 85% of patients with this form of diabetes have been found to have detectable circulating antibody against islet cells at the onset of the disease, which suggests that diabetes of juvenile onset may be considered an autoimmune disease.3 Thus, the reported association with other autoimmune endocrinopathies is not surprising.4'5 Our patient had an autoimmune polyendocrinopathy prior to presentation with systemic lupus erythematosus, as evidenced by the presence of circulating antibodies to thyroid and adrenal antigens. It is reasonable to assume that she may also have had anti-islet-cell antibody formation. A previous report described a patient with transient chemical diabetes after the initiation of prednisone therapy for systemic lupus erythematosus; antibodies directed against cultured insulinoma cells were detected.0 In our patient insulin-dependent diabetes predated systemic lupus erythematosus and was accompanied by autoimmune thyroiditis. Thus, not only did a tissue antigen profile indicate susceptibility to both juvenile insulindependent diabetes mellitus and systemic lupus erythematosus, but also both diseases developed in association with autoantibody formation against at least two other endocrine glands; therefore, our patient had a wide-ranging and ultimately fatal autoimmune disease. In patients with antigens such as B8, in whom autoimmune disease occurs, vigilance is required so that, should other autoimmune states such as systemic lupus erythematosus evolve, they may be readily identified. The silent evolution of this disease in situations in which it was not originally suspected, such as membranous nephropathy,7 suggests that autoantibody formation against nuclear antigens might have been present in our patient at the onset of diabetes and that full clinical expression of the disease did not become apparent for 2 years. It is not unusual to perform serial autoantibody profiles in persons with autoimmune diseases, but our case, as well as that originally de-

scribed,6 in which glucose intolerance improved with control of the patient's lupus state, indicates that such testing may prove fruitful in providing better information for patient management as well as broadening our understanding of the underlying processes in autoimmune disease. SEAN O'REGAN, MD

Department of nephrology H6pital Sainte-Justine Montreal, PQ

References 1. WANEBO HJ, RAWSON RW: Lupus erythematosus complicated by the Chiari-Frommel syndrome and autoimmune thyroiditis. Arch Intern Med 124: 619, 1969 2. DAUSSET J, DEGOS L, HORS J: The association of the HL-A antigens with diseases. Clin Immunol Immunopathol 3: 127, 1974 3. NERUP J, PLATZ P, RYDER LP, et al:

HLA islet cell antibodies, and types of diabetes mellitus. Diabetes 27 (suppi 1): 247, 1978 4. BOTTAZZO GF, FLORIN-CHRISTENSEN

A, DONAICH D: Islet cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 2: 1279, 1974 5. MACCUISM AC, BARNES EW, IRVINE

WJ, et al: Antibodies to pancreatic islet cells in insulin-dependent diabetics with coexistent autoimmune disease. Ibid, p 1529 6. FRUMAN LS: Diabetes mellitus, islet cell antibodies and HLA-B8 in a patient with systemic lupus erythematosus. Am J Dis Child 131: 1252, 1977 7. Luwr SA, BURRE B, MICHAEL AF,

et al: Extramembranous glomerulonephritis in childhood: relationship to systemic lupus erythematosus. J Pcdiatr 88: 394, 1976

Music therapy To the editor: I applaud CMAJ for publishing the article on music therapy in palliative care by S. Munro and Dr. B. Mount (Can Med Assoc J 119: 1029, 1978). I wish to report an aspect of music therapy that has received little attention.

The Regional Psychiatric Centre in Abbotsford, BC is a 138-bed prison hospital that was established in 1972 to provide psychiatric treatment to emotionally disturbed or mentally ill federal offenders. In 1975 the centre began a program with a voluntary music appreciation group consisting of inmate patients. Every Tuesday afternoon the group

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