Pulmonary cryptosporidiosis and immune reconstitution inflammatory syndrome: a case report and review

INTRODUCTION

Cryptosporidium is a protozoan parasite that typically invades the small bowel and causes a diarrhoeal illness. Although cryptosporidiosis may affect immunocompetent hosts, it is particularly prevalent and severe in those with AIDS. ¹ In addition to small bowel involvement, cryptosporidium may affect extraintestinal sites, such as the biliary tract and the lungs. Pulmonary cryptosporidiosis is uncommon, with only about 100 cases reported in the literature.

Another unusual manifestation of cryptosporidial infection is the development of immune reconstitution inflammatory syndrome (IRIS) following the initiation of antiretroviral therapy (ART).^2,3 We describe an AIDS patient with intestinal and pulmonary cryptosporidiosis who developed intestinal and pulmonary IRIS following the initiation of ART.

CASE

A 53-year-old West African man with a history of AIDS presented with four months of watery diarrhoea and 30 pounds (13.6 kg) of weight loss. He lived in the USA, traveled frequently to West Africa and had not been taking ART for many years.

He was initially admitted to the intensive care unit with profound metabolic acidosis and hypokalaemia. His CD4 count was 14 cells/mm³, HIV-1 viral load was 2,600,000 copies/mL and stool studies soon revealed Cryptosporidium oocysts. Nitazoxanide, loperamide, octreotide and total parenteral nutrition were initiated; his diarrhoea and electrolyte abnormalities improved, and on hospital day 5 raltegravir, emtricitabine and tenofovir were started.

On hospital day 9 he developed a productive cough. Chest X-ray was unremarkable, but sputum microscopy showed Cryptosporidium oocysts. Other sputum studies, including four acid fast bacilli smears and cultures and a Pneumocystis jirovecii direct fluorescent antibody smear, were negative. Treatment with nitazoxanide and ART was continued, and after a total of 28 days his symptoms had improved. He was discharged to continue these medications at home.

Seventeen days after discharge, the patient was re-admitted with worsening diarrhoea and cough. At this time his CD4 count was 325 cells/mm³ and HIV-1 viral load was 140 copies/mL. Stool and sputum studies did not reveal cryptosporidiosis or any other active infection. Chest X-ray now demonstrated reticular opacities at both lung bases. Computed tomography of the chest showed diffuse bilateral patchy pulmonary infiltrates (Figure 1), and therefore bronchoscopy, bronchoalveolar lavage (BAL) and transbronchial biopsy were performed. Gram stain and cultures from the BAL were negative, including fungal and mycobacterial cultures, and Cryptosporidium was not seen. Biopsy showed inflamed bronchial and alveolar tissue, with no microorganisms or viral changes, although light growth of Klebsiella pneumoniae and Enterococcus faecalis was noted on the tissue culture. OPEN IN VIEWER

Due to the normal BAL studies and only light bacterial growth on the tissue culture, the tissue culture findings were not thought to represent active infection. Instead, the patient's worsening pulmonary and gastrointestinal symptoms, which began during the restoration of immune function with ART, were attributed to pulmonary and gastrointestinal IRIS. Empiric treatment with broad-spectrum antibiotic and antifungal therapy was stopped after a total of five days, his symptoms improved after 20 days, and he was discharged home.

DISCUSSION

To our knowledge, this case is the first published report of pulmonary IRIS following cryptosporidiosis. This diagnosis is exceptionally rare, not only because pulmonary cryptosporidiosis is uncommon, but also because IRIS is not typically associated with cryptosporidial infections.

Pulmonary cryptosporidiosis is thought to arise from either the aspiration of oocysts while vomiting, the haematogenous spread of infection from the bowel to the lungs or the direct inhalation of aerosolized oocysts. A 1996 review of pulmonary cryptosporidiosis reported only 57 published cases, ⁴ and few have been reported since.^5–10 However, a 1995 trial that screened the sputum of AIDS patients with intestinal cryptosporidiosis found that 16% also had Cryptosporidium in sputum samples, ¹¹ and a recent study that used polymerase chain reaction to examine the sputum of HIV-negative children with intestinal cryptosporidiosis found that one-third also had respiratory involvement. ¹² These studies indicate that pulmonary cryptosporidiosis may be more common than is widely reported.

The optimal treatment of cryptosporidial infection at any site has not been well-defined, particularly in patients with AIDS. Nitazoxanide and paromomycin are commonly used as antiparasitic agents; however, a 2007 meta-analysis found no evidence that these medications improved symptoms or hastened oocyte clearance in AIDS patients with intestinal cryptosporidiosis. ¹³

In patients with AIDS, the mainstay of cryptosporidiosis treatment is the improvement of immune function with ART. In addition to bolstering immunity, some protease inhibitors have been shown to have direct anti-cryptosporidial activity, ¹⁴ and multiple studies have described the resolution of cryptosporidiosis following the initiation of ART. ¹⁵ Current guidelines recommend the immediate initiation of ART in patients with AIDS and cryptosporidiosis. ¹⁶

A concern when initiating ART in acutely infected patients is the development of IRIS; however, IRIS is rarely described in association with cryptosporidiosis. A literature review reveals only two such cases, one following terminal ileitis ² and the other following cryptosporidial cholangitis. ³

This case demonstrates that IRIS with pulmonary involvement following the initiation of ART in patients with cryptosporidiosis is also possible. Although it is exceedingly rare, this case shows that IRIS should be considered in patients with pulmonary cryptosporidiosis who develop worsening respiratory symptoms after beginning ART. Additionally, because pulmonary involvement may be under-recognized in patients with intestinal cryptosporidiosis, ¹² pulmonary IRIS should also be considered in patients with intestinal cryptosporidiosis who develop unexplained respiratory symptoms after initiating ART.