Insidious Onset of Breathlessness,
Cough, and Fever in a Patient Following
Combination Chemotherapy

Case History

A 56-year-old man was diagnosed with stage IIIS diffuse large cell non-Hodgkin's lymphoma involving cervical and intra-abdominal lymph nodes and spleen. He received 6 cycles of combination chemotherapy containing doxorubicin, vincristine, cyclophosphamide and prednisolone (CHOP). Computed tomography (CT) scan after 6 cycles of CHOP showed no residual lymphadenopathy or splenic deposits but there was bilateral ground glass appearance of the lungs with 'tree-in-bud' opacities at the lung bases. Chest X-ray (CXR) showed patchy infiltration and mild bilateral consolidation (Figure 1). The patient complained of increasing cough with whitish sputum for about 6 weeks, exertional dyspnoea, and swinging fever.

Figure 1. Chest X-ray showing patchy infiltration.

At physical examination, there was decreased bilateral breath sounds associated with scattered crepitations. Arterial blood gas showed type I respiratory failure. Bronchoscopy and transbronchial lung biopsy was done for further investigation of atypical chest infection. No endobronchial lesion was seen but bronchoalveolar lavage showed the presence of Pneumocystis carinii by both modified Toluidine Blue O stain and Grocott stain. Diagnosis of
P carinii pneumonia (PCP) was confirmed and the patient was treated with intravenous trimethoprim-sulfamethoxazole for 2 weeks followed by a further course of oral trimethoprim-sulfamethoxazole for 2 weeks. He improved with decreasing chest symptoms, his fever settled, and he successfully reduced additional oxygen intake. Serial chest X-ray showed decreasing lung infiltrate.

Discussion

P carinii is more appropriately classified as a fungus than a protozoan based on gene sequence and cell wall constituents. Whether the manifestation is due to reinfection or reactivation is controversial. In an immunocompetent host, the infection is asymptomatic.¹ In an immunocompromised host, such as individuals with AIDS, those receiving cytotoxic drugs, and malnourished children, the infection causes pneumonia. Defective T-cell immunity is the principal risk factor. Cases of disseminated infection are also reported.

Typical presentations are fever, non-productive cough, tachypnoea and hypoxaemia. CXR may be normal during the early stage. Subsequent radiographic examination usually reveals diffuse interstitial infiltrates, which often originate at the hilum and extend peripherally in a butterfly pattern. High resolution CT scan shows characteristic bilateral ground glass appearance even when there is little to see on the CXR. Diagnosis of PCP relies on microscopic visualisation of the organism by immunofluorescence staining using monoclonal antibodies or older staining methods such as silver staining or Wright-Giemsa. However, the organism cannot be grown in vitro.

Recently, polymerase chain reaction detection of the P carinii genome for demonstrating the organism in induced sputum or blood has been introduced.^2,3 Patients are treated with trimethoprim-sulfamethoxazole (trimethoprim 15 to 20 mg/kg divided into 3 to 4 daily doses).⁴ For patients who are intolerant to this combination, alternative therapies include intravenous pentamidine, dapsone and trimethoprim, and clindamycin-primaquine, but the response rate is lower. In patients with moderate to severe PCP (PaO 2 <70 mm), systemic corticosteroids have been shown to decrease mortality. Trimethoprim-sulfamethoxazole is highly effective as prophylaxis against PCP and should be considered for high-risk patients.

References

1. Sepkowitz KA. Pneumocystis carinii pneumonia in patient without AIDS. Clin Infect Dis 1993:17 (Suppl 2):416-422.
2. Lipschik GY, Gill VJ, Lundgren JD. Improved diagnosis of Pneumocystis carinii infection by polymerase chain reaction in induced sputum or blood. Lancet 1992;340:203-206.
3. Kovacs JA, Ng VL, Masur H, et al. Diagnosis of Pneumocystis carinii pneumonia: improved detection in sputum with the use of monoclonal antibodies. N Engl J Med 1988;318: 589-593.
4. Hughes WT, Rivera GK, Schell MJ, et al. Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med 1987;316:1627-1632.

Dr WM Ho
Medical Officer

Dr CW Yu
House Officer

Department of Clinical Oncology
Prince of Wales Hospital
Hong Kong
China