Case report of Aspergillus osteomyelitis of the ribs in an immunocompetent patient.

Aspergillus is a saprophytic fungus which is universally found in the environment. Most people breathe in the spores of Aspergillus every day without development of disease. It commonly affects immunocompromised hosts. There are only few reported cases in an immunocompetent host. It most commonly affects the respiratory system, causing superficial or invasive disease. It also affects the skin, brain and eye in severely immunocompromised patients. Aspergillosis of the bone is extremely rare. Amongst all the reported cases of invasive aspergillosis the incidence of osteomyelitis is less than three percent. In these cases commonly of the spine is reported. We present a case of Aspergillus osteomyelitis of the ribs in an immunocompetent host.

INTRODUCTION

Aspergillus is a ubiquitous saprophytic fungus universally found in nature. Aspergillus exists in two forms: spores and hyphae, with spores being the infective form. Most people breathe in Aspergillus spores daily without being affected. Of the 300 known species of Aspergillus only a few of them cause opportunistic infections.[1] The vast majority of disease is caused by A. fumigatus, followed by A. flavus and A. niger.

Invasive Aspergillosis (IA) is a disease generally seen in immunocompromised patients. It commonly affects the lungs, but can spread and invade other organs in the body. Population based studies suggest a rate of one to two cases of invasive aspergillosis per 100,000 people per year with the mortality increasing by 357% in the United States from 1980 to 1997.[2] This has been attributed to the increasing number and longer survival of immunocompromised patients with newer modalities of treatment.

CASE REPORT

A 45-year-old lady presented with a history of right upper abdominal pain for six months. The pain worsened on deep inspiration and on applying pressure over the chest wall. It had been progressively worsening in severity. She gave a history of loss of appetite and loss of weight of approximately five kilograms during this period. There was no history of cough, fever or trauma. She gave a history of diabetes mellitus for five years, which was adequately controlled with oral hypoglycemic agents.

On examination, she had tenderness over her right upper abdomen. She had no underlying organomegaly, bony tenderness or lung findings. Investigations were normal, except an elevated ESR and CRP. Imaging studies, including chest radiograph, abdomen ultrasound and a bone scan were inconclusive. She was asked to follow-up after two months.

She presented again after six months with increased pain over the right upper quadrant. On examination, she was found to have a tender swelling on the right ninth and tenth ribs, measuring 3 × 2 cm each. With a tender swelling, and elevated inflammatory markers, a diagnosis of Osteomyelitis involving the ribs was made, and she underwent a computed tomography (CT) scan to confirm the same.

CT of the chest and abdomen revealed a swelling over the lower end of the ninth and tenth ribs, associated with thickening of the underlying pleura, and necrosis of adjoining ribs and costochondral junctions. A screening ultrasound showed an 8cc collection with surrounding necrosis, which was aspirated under guidance. The histopathology report showed areas of necrosis on histology, with a lymphohistiocytic inflammatory infiltrate [Figure 1]. The aspirates were also sent for cultures, which grew Aspergillus fumigatus after two weeks of incubation [Figure 2]. This report was unexpected, as the patient did not have any traditional risk factors for Aspergillosis. She had diabetes mellitus, which was well controlled, without evidence of any complications.

Figure 1

The histopathology report of the necrotic bone showed dense inflammatory granulation tissue, necrotic bone and narrow branching septate fungal hyphae

Figure 2

PAS (Periodic acid-Schiff) stain of the necrotic bone showing branching septate fungal hyphae diagnostic of Aspergillus fumigatus

She underwent surgical debridement, and was initiated on Voriconazole. She showed clinical improvement after the same

DISCUSSION

Aspergillus is a fungus found universally in nature. It commonly causes disease in immunocompromised patients. This disease is well documented in solid organ recipients, involving over 30% patients with lung transplants, followed by chronic granulomatous disease and acute leukemias.[2]

The epidemiology of aspergillosis differs slightly in developing countries. In addition to the similar risk factors as in the western population, old tuberculous cavities, uncontrolled diabetes, intracranial surgery and cardiac device implantation are also found to increase the risk of Aspergillus infections.[3]

The spores of Aspergillus are unusually small compared to other fungi, which allows for easy inhalation.[1] Within 4-5 h of inhalation, the spores swell up, and within 12-14 h, germinate to form invasive hyphae. Cell mediated immunity plays a vital role in defense against aspergillosis, with macrophages and NK cells being the first line of defense, followed by activation of NAPDH oxidase and recruitment of T cells. The importance of NADPH is highlighted by the fact that patients with chronic granulomatous disease, who are unable to produce NADPH, have one of the highest incidences of Aspergillus infections. Pulmonary involvement is the commonest manifestation of aspergillosis, seen in 80-90% of patients.[4]

Aspergillosis of the bone

The most common cause of fungal osteomyelitis is Candida.[5] Aspergillosis of the bone is extremely rare and among cases of reported invasive aspergillosis the incidence of osteomyelitis is found to be lesser than three percent.[5] The osteomyelitis commonly involves the vertebral bodies and has been seen to mimic tuberculous osteomyelitis.[6]

Also more than 50% of the patients do not have fever. Osteomyelitis can occur by direct implantation (either traumatic or iatrogenic), hematogenous spread or by contiguity. There are very few case reports of Aspergillus osteomyelitis in an immunocompetent patient,[7] with most of the case reports showing involvement of the spine.

We came across only one case described in literature, where Aspergillus osteomyelitis of the rib and vertebral bodies was diagnosed in an immunocompetent IV drug user.[8] The presentation was remarkably similar to our patient's, with hypochondrial pain for more than four months and a localized swelling over the lower ribs. Diagnosis was proven by aspiration and culture of the localized collection. Treatment was with debridement and a prolonged course of antifungal therapy.[8]

The natural history of such infections is to have a protracted course, with late diagnosis being the rule rather than the exception.[1] In a recent review of 106 patients with rib osteomyelitis, the mean duration to diagnosis of fungal osteomyelitis was 32 weeks.[1]

Our case highlights the increasing incidence of this previously rare disease, which is a reflection of an increase in the number of people living with immunosuppression. Thus, in a patient with osteomyelitis or soft tissue infections, culture and histopathological examination is very essential to avoid missing fungal infections. This is especially true in patients who are elderly, diabetics or otherwise debilitated.

To our knowledge this is the second case report of such a manifestation of Aspergillus osteomyelitis involving the ribs without pulmonary involvement, and the first such case in an immunocompetent host.

CONCLUSION

It is important to consider the very rare possibility of a fungal osteomyelitis even in an immunocompetent patient. This is important in view of an ever increasing number of diabetic and elderly population. However, it is a diagnosis which can only be made with histopathology and culture reports.