Pneumonia due to Mycoplasma pneumoniae with transient proteinuria.

ABSTRACT: Mycoplasma pneumoniae pneumonia can be associated with several systemic features. This report illustrates a case of M pneumoniae pneumonia with transient proteinuria in an adult who recovered completely. Direct infection of the kidneys or an immunologic mechanism may have been the underlying cause. This patient also had simultaneous pharyngitis caused by group A [beta]-hemolytic streptococci. Various clinical possibilities with respect to pneumonia, pharyngitis, and proteinuria are briefly reviewed.

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MYCOPLASMA PNELMONIAE is an important etiologic agent of community-acquired atypical pneumonia in adults, accounting for 15% to 20% of all cases. (1) The extrapulmonary features of the disease include arthritis, pericarditis, myocarclitis, disseminated intravascular coagulation, meningitis, encephalitis, optic neuritis, Guillian-Barre syndrome, transverse myelitis, cerebellar ataxia, and dermatologic lesions such as erythema mutiforme. (1,2) This report describes a young adult with M pneumoniae pneumonia and transient proteinuria, followed by complete recovery.

CASE REPORT

A 23-year-old man was seen after 2 weeks of throat pain and cough, with left-sided chest pain and fever that had developed 2 days before admission. The patient's 2-year-old son had recovered from streptococcal pharyngitis just before the onset of his illness. Physical examination revealed blood pressure of 142/78 mm Hg, respiratory rate 32/mm, temperature 37.5[degrees]C, exudative pharyngitis, and dullness and decreased breath sounds over the left lower chest. Results of cardiovascular, gastrointestinal, and nervous system examinations were normal. There was no edema. The P[o.sub.2] value was 52 mm Hg on room air. Total leukocyte count was 20,200/[mu].L (neutrophils 70%, band forms 20%, lymphocytes 3%, and monocytes 7%), hemoglobin value 14.9 g/dL, blood urea nitrogen value 11 mg/dL, and creatinine value 0.8 mg/dL. Urine examination revealed a protein value of >300 mg/dL, 3 to 5 white blood cells and 3 to 5 red blood cells per high power field, and granular casts. Blood and urine cultures were negative. A 24- hour urine protein estimation was 2,349 mg. Chest radiograph showed a left lower lobe infiltrate. Gram's stain of sputum showed many white blood cells, rare epithelial cells, few gram-positive bacilli, gram-negative bacilli, and few gram-positive cocci in clusters and pairs. Sputum culture grew normal respiratory flora with group A [beta]-hemolytic streptococci. A throat culture grew group A [beta]-hemolytic streptococci. A rapid strep test on the throat swab was positive. Enzyme-linked immunosorbent assay showed an M pneumoniae IgM antibody titer of 1,121 mU/mL (negative <770 mU/mL). Tests for antinuclear antibody, antibody to human immunodeficiency virus, and legionella urinary antigen were negative. Other extensive testing was not considered clinically justified because of the presence of an infective pneumonia, the transient nature of the illness, and the rapid improvement. He was treated with doxycycline, 100 mg twice daily for 2 weeks, followed by complete recovery. On follow-up at 1 month, 24-hour prot ein estimation was 94 mg, urinalysis was unremarkable, and M pneumoniae IgM titer was 1,470 mU/mL. Renal biopsy was deferred because of the steady clinical improvement.

DISCUSSION

The cause of pneumonia in this patient was considered to be M pneumoniae on the basis of serology with high IgM titers. A temporal association of a transient acute infection such as mycoplasmal pneumonia and proteinuria that subsided with the recovery of the illness points to a causative relationship. Possible explanations for this patient's proteinuria include direct infection of the kidneys by the organism and immunologic mechanisms. Mild proteinuria would have been explained by the febrile nature of the illness, but the severe proteinuria in this case suggested otherwise. Glomerular involvement was implied in our patient because of the active urinary sediment. Renal biopsy was deferred because of the concurrent acute pneumonia.

Renal involvement with proteinuria is unusual in M pneumoniae pneumonia, especially in adults. Most reports in the literature pertain to the pediatric population. In a series of 148 patients over a 14-year period from Mayo Clinic, no patients had renal involvement. (2) There is only one previous report of massive proteinuria associated with M pneumoniae infection in a 5-year-old girl. (3) The proteinuria was transient, and the findings on kidney biopsy resembled minimal change nephrotic syndrome. Mycoplasma antigen was not detected by indirect immunofluorscence. The authors postulated a specific soluble factor altering the permeability of the glomerular basement membrane. Mycoplasma pneumoniae has been linked to renal diseases such as mesangiocapillary glomerulonephritis type II, acute glomerulonephritis IgA nephritis, interstitial nephritis, and asymptomatic glomerulonephritis. (4-7) None of these cases were associated with massive proteinuria. Mycoplasma pneumoniae antigen was demonstrated along the glomeru lar capillary walls, mesangium, and Bowman's capsule in an 11-year-old girl who presented with pneumonia and acute glomerulonephritis. (7) Subendothelial and subepithelial electron dense deposits were also noted, suggesting a role for immune complexes in the pathogenesis of glomerular injury.

This case also represents some interesting clinical scenarios. It illustrates the real dilemma faced by clinicians who encounter less than "black and white" cases during routine practice. We believed that the group A [beta]-hemolytic streptococci grown from the sputum was actually from the pharyngitis because of specimen contamination. This was supported by the multiple organisms seen on Gram's stain. Group A [beta]-hemolytic streptococci is unlikely to be the cause of the pneumonia in this patient for several reasons. Group A [beta]-hemolytic streptococcal pneumonia has been reported mainly in military camp epidemics caused by highly virulent strains. (8) The other associations of this unusual variety of pneumonia are those preceding viral infections such as influenza, measles, or varicella or chronic pulmonary disease. Pneumonia is characterized by bronchopneumonia, and consolidation is uncommon? The presence of normal respiratory flora in the sputum culture indicates a lack of pure growth of group A [beta ]-hemolytic streptococci. The negative blood culture also argues against the diagnosis of group A [beta]-hemolytic streptococcal pneumonia.

It is unlikely that the group A [beta]-hemolytic streptococci caused glomerular involvement and proteinuria in the acute stage. Acute glomerulo nephritis following streptococcal pharyngitis usually develops 1 or 2 weeks after the pharyngitis, and the clinical picture is nephritic with red blood cells and RBC casts in the urine, hypertension, and azotemia. (10) The manifestation of proteinuria without azotemia and hypertension is not consistent with this diagnosis.

The presence of lobar infiltrate is an unusual presentation in mycoplasmal pneumonia. Although diffuse reticulonodular or interstitial infiltrates are the classical radiographic features, a lobar pattern of involvement is also possible in mycoplasmal pneumonia. (11)

This patient's presentation of both streptococcal pharyngitis and mycoplasmal pneumonia is an uncommon and interesting association. We presumed that the streptococcal pharyngitis was ongoing for the previous 2 weeks and the mycoplasmal pneumonia appeared later in the course of the illness. Proteinuria subsided with complete cure of the pneumonia by the antibiotic therapy. Complete recovery from the proteinuria without residual renal impairment is noteworthy in this case.

References

(1.) Foy HM: Mycoplasma pneumoniae pneumonia: current perspectives. Clin Infect Dis 1999; 28:237

(2.) Mansel JK, Rosenow EC, Smith TF, et al: Mycoplasma pneumoniae pneumonia. Chest 1989; 95:639-646

(3.) Akano N, Yoshioka K, Matsui K, et al: Transient massive proteinuria associated with Mycoplosma pneumoniae infection. Am J Kidney Dis 1991; 18:123-125

(4.) Von Bonsdorff M, Ponka A, Tornroth T: Mycoplasmal pneumonia associated with mesangiocapillary glomerulonephritis type II (dense deposit disease). Acta Med Scand 1984; 216:427-429

(5.) Kanayama Y, Shiota K, Kotumi K, et al: Mycoplasma pneumoniae pneumonia associated with IgA nephropathy. Scand J Infect Dis 1982; 14:231-233

(6.) Pasternack A, Helin H, Vanttinen T, et al: Acute tubulointerstitial nephritis in a patient with Mycoplasma pneumoniae infection. Scand J Infect Dis 1979; 11:85-87

(7.) Vitullo BB, O'Regan S, de Chadarevian JP, et al: Mycoplasma pneumonia associated with acute glomerulonephritis. Nephron 1978; 21:284-288

(8.) Centers for Disease Control and Prevention: Acute rheumatic fever at a navy training center--San Diego, California. MMWR Morb Mortal Wkly Rep 1988; 37:101-104

(9.) Bisno AL, Stevens DL: Streptococcus pyogenes (including streptococcal toxic shock syndrome and necrotizing fasciitis). Principles and Practice of Infectious Diseases. Mandell GL, Bennett JE, Dolin R (eds). Philadelphia, Churchill-Livingstone, 5th Ed, 2000, pp 2102-2116

(10.) Stollerman GH: Streptococcus pyogenes (group A streptococci). Infectious Diseases. Gorbach SL, Bartlett JG, Blacklow NR (eds). Philadelphia, WB Saunders Co, 2nd Ed, 1998, pp 1703-1719

(11.) Cassell CH, Cole BC: Mycoplasmas as agents of human disease. N Engl J Med 1981; 304:80-89

RELATED ARTICLE: KEY POINTS

* Mycoplasma pneumoniae causes 15% to 20% of community-acquired atypical pneumonia.

* Proteinuria is an unusual manifestation of M pneumoniae pneumonia, presumably due to direct infection or to an immunologic mechanism.

* The presence of group A [beta]-hemolytic streptococci in the sputum confounded the clinical picture in this patient.

From the Department of Medicine, Huron Hospital/Cleveland Clinic Health System, Cleveland, Ohio.

Reprint requests to P. Dileep Kumar, MD, 2885 Heritage Dr, Fort Gratiot, MI 48059.