An unusual recurrent case of Cryptococcal sacroiliitis in an immunocompetent elderly female in Rajasthan, India

Abstract

A 70-year-old female presented with left sided low back pain. There was no history of any co-morbidities or immunocompromised state. Skeletal cryptococcosis was confirmed bsaed on culture and histopathology, along with pulmonary involvement. After a month of oral antifungal therapy, the patient's symptoms resolved, but an abscess relapsed at the same site, which was treated with a combination of IV Amphotericin B and 5-flucytosine followed by oral fluconazole, with no recurrence or complaints reported in subsequent follow-up.

1. Introduction

Cryptococcus lives in environments all over the globe. Cryptococcal osteomyelitis is an unusual infection that is usually associated with an underlying immunocompromised state, trauma, contiguous neural infection, or hematogenous spread from pulmonary foci. Despite the fact that pulmonary involvement occurs through inhalation from the environment, the majority of exposed individuals never become ill. The literature suggests that skeletal cryptococcosis is manifested in only 5%–10% of recognised cases of disseminated cryptococcosis, and that isolated skeletal disease without evidence of other tissue involvement is even less common [1]. The objective of this clinical case report is to highlight the rare fungal aetiology associated with iliac bone abscess to avoid incorrect diagnosis and prompt management of the case, leading to better patient recovery, an improved prognosis, and preventing relapse.

2. Case presentation

A 70-year-old female from Jaipur, India, presented to a private practitioner [day 0] with hip pain that had been going on for almost a month, was dull and sharp at times, and was not relieved by local analgesics. She was prescribed oral analgesics and advised to undergo physiotherapy. Pain worsened after physiotherapy, necessitating additional testing. A less than a cm sized bulge was noticed at the left sacroiliac joint on general physical examination. An MRI was performed on day +5 that revealed a well-defined, irregularly marginated osteolytic focal lesion in the left iliac bone, as well as joint effusion, surrounding oedema, and marrow infiltration suggestive of an infectious aetiology, tuberculosis, or, less likely, metastasis. [Fig. 1A, Fig. 1B, Fig. 1CA and B,C.

Fig. 1A.

Coronal T1 WI shows hypo intense lesion in the left iliac bone.

Fig. 1B.

T1 weighted image of the pelvis shows involvement of the left iliac bone with T1 hypointense collection in the surrounding soft tissue.

Fig. 1C.

T2 weighted images showing bone involvement and collection.

A CT-guided biopsy [Day +6] was performed and the abscess was drained (20 mL) [Fig. 2]. A sample was sent for further laboratory examinations to rule out possible underlying etiologies, namely 1) infectious, 2) tubercular, and 3) metastasis. On microscopy, fragments of necrotic bone and occasional multinucleate giant cells were seen, but no caseous necrosis. Occasional hyphae like fragments were noted, which gave the impression of acute on chronic osteomyelitis with a suspicion of fungal infection. No aerobic and anaerobic bacterial growth was observed. Cryptococcus spp. were isolated on Sabouraud dextrose agar plates, and further speciation was done by Vitek MS, which reported Cryptococcus neoformans. Cryptococcal antigen testing in serum was not performed.

Fig. 2.

Image of CT guided biopsy of the left iliac bone , note erosion involving the left sacral ala and the right ilium.

Extra-pulmonary TB was ruled out by a negative Mantoux test, no acid-fast bacilli seen on Ziehl-Neelsen staining, no growth on MGIT culture, and a negative result on GeneXpert MTB. To detect pulmonary involvement, an HRCT thorax was done, which gives an impression of bronchitis and bilateral interstitial pneumonitis along with enlarged lymph nodes in pre & paratracheal region, pre subcarinal, aorto pulmonary window, bilateral hilar region, with the largest one measuring 24 × 20 mm.

The bone scan revealed no evidence of metastasis. Tumor markers, namely alpha-fetoprotein (2.45; normal: 0–40 ng/ml), carcinoembryonic antigen (0.78; normal: 0–2.5 ng/ml), cancer antigen-125 (10.90; normal: 0–35 units/ml), and adenosine deaminase (35; normal: <40 U/L), were within the normal range, and serum protein electrophoresis reported a normal study. On PET-CT, a hyper metabolic lytic lesion was reported in the left iliac bone with fluid collection [Fig. 3A]. Along with that, the PET scan revealed multiple hyper metabolic enlargements and centimetre-sized right supra and infraclavicular, mediastinal, bilateral cardio-phrenic, abdominal, and retroperitoneal lymphadenopathy [Fig. 3B] and bilateral ground glass haziness suggestive of an infectious aetiology, but no evidence of malignant foci, which ruled out osteolytic lesions secondary to metastasis.

Fig. 3A.

PET CT showing FDG avid lesion in left ilium and surrounding soft tissue.

Fig. 3B.

PET CT showing abnormal FDG uptake in the region of left ilium and mediastinum.

Considering unexplained multiple pulmonary lymph node involvement, an angiotensin converting enzyme (ACE) level was done, which reported a normal parameter ruling out sarcoidosis. Patient serum was found negative for HBsAg and non-reactive for HIV–I, HIV-II, and HCV anti-bodies. CD4 cell counts were within the normal range, and HLA-B-27 was found negative. A white blood cell count was 8.03 × 106 cells/L with 70.7% neutrophils, 21.8% lymphocytes, 2.9% monocytes, and 3.6% eosinophils. Liver and renal function tests were within normal range. ESR was raised (50; normal range: 0–20). The patient was non hypertensive with an HbA1c of 6.5. The patient had a history of falling 5 months (−150 days) prior to the presenting complaints, which was treated with topical analgesics. There was no history of fever, diabetes, an immunocompromised state, or weight loss.

As cases of invasive aspergillosis are more commonly seen in India than other invasive pulmonary infections, the patient was started empirically on oral Voriconazole 200 mg BD for 4 weeks and considering generalised lymphadenopathy in a nation with a TB epidemic, a 4-week therapeutic trial of anti-tubercular therapy was started [Day +7], which was stopped within a week due to patient non compliance and the anti-tubercular drug's side effects. Abscess resolved with Voriconazole and the patient was discharged at her request.

The patient presented with pain and the reappearance of a bulge at the same site nearly 4 months after the first episode [Day +120]. A CT scan of this fluctuant nodule depicted a hypoechoic lesion with no increased vascularity, and the nodule was ultrasound guided drained (a 25-ml abscess) and sent for laboratory examination.

On day 121, many budding yeast cells were reported on the KOH mount. Similarly, capsule and budding yeast cells were found in the India ink preparation [Fig. 4 A,B] which was confirmed by a positive serum Cryptococcal antigen test (1:80 titre) [FungiXpert Cryptococcal Capsular Polysaccharide Detection K Set (Lateral Flow Assay)], giving an overall impression favouring Cryptococcal Sacroiliitis. At day 122, histopathology reported inflammatory infiltrates with occasional giant cells and neutrophils. Sections show many round to oval fungal organisms that were found PAS positive with mucicarmine and alcian blue positive capsules, giving an overall histo-morphology impression in favour of cryptococcosis. Occasional pus cells were seen on Gram staining, but no microorganisms were seen in the submitted sample. There was no growth on the aerobic plate or broth culture on day 123.

Fig:4.

India ink staining demonstrating Capsule (Fig. 4A) and budding yeast cells (Fig. 4B)

To rule out invasive Aspergillosis, the patient's serum was tested for fungal markers, with beta-d glucan being indeterminate (76.24; positive >80 pg/ml) and galactomannan being negative (0.44; positive >0.50 pg/ml). Cryptococcus species were isolated on sabouraud dextrose agar plates on second episode as well [Day +125], and further speciation was done by Vitek MS as well as MALDI TOF, confirming that the isolate was Cryptococcus neoformans. The patient was started on a 14-day course of liposomal amphotericin B 250 mg and IV 5-flucytosine 200 mg qid, followed by oral fluconazole 200 mg BD for 4 weeks, which resulted in the resolution of abscess as well as symptoms. In both episodes, No surgical debridement of the lesion was performed. Since then, the patient is asymptomatic, and no relapses were reported on a subsequent examination.

3. Discussion

This is the first case of skeletal cryptococcoal infection at our institution that was managed with combination anti-fungal therapy without surgical debridement. Cryptococcus neoformans is a fungus that lives in the environment around the globe. People can become infected with C. neoformans after breathing in the microscopic yeast, although most people who are exposed to the fungus never develop disease. C. neoformans infections are rare in people who are otherwise healthy; most cases occur in people who have weakened immune systems, particularly those who have advanced HIV/AIDS [2].

Skeletal cryptococcal infections are a very uncommon manifestation of disseminated cryptococcal disease, occurring in only 5%–10% of patients with disseminated disease [1], with isolated skeletal cryptococcal infections occurring even less commonly. It is felt that most skeletal cryptococcal infections arise secondary to hematogenous spread from a primary pulmonary infection. Other potential sources are trauma, embolic phenomena, contiguous skin infection, or contiguous neural infection [3]. Isolated focal iliac bone cryptococcosis is unusual but may occur in healthy individuals after everyday exposure to the organism [4]. Herein, the patient had bilateral pulmonary pneumonitis & bronchitis on HRCT along with multiple lymphadenopathy with no evidence of TB bacilli implying that the isolate most likely originated from environmental bird droppings and has disseminated from the pulmonary lesion to the iliac bone.

The radiological findings of an iliac cryptococcal abscess were nonspecific. A definitive diagnosis was made on the basis of histopathological and fungal examinations of the gluteal abscess. Clinicians must be alert to this disease and be able to identify the particular fungal strain.

No standard treatment protocol exists for skeletal cryptococcosis [5,6]. The Infectious Disease Society of America recommends oral fluconazole (400 mg per day for 6–12 months) as the treatment of choice for immunocompetent patients with non meningeal, non-pulmonary cryptococcosis [7]. But in most cases, a combination of anti-fungal therapy along with surgical debridement has been used to treat many patients with skeletal cryptococcosis [8]. As the patient refused surgical intervention, we were compelled to resort to anti-fungal drug therapy. Although combination therapy with AMB and 5-FC did not outperform AMB alone in terms of improving the mortality rate, combined therapy is still recommended [[8], [9], [10]].

In this case, after ultrasound guided drainage of the abscess, combination therapy of Amphotericin B and 5-flucytosine for 14 days followed by oral fluconazole for the next 4 weeks was found quite effective for resolving bone cryptococcosis. The patient was monitored for relapses or other medical issues related to the case at the time, but no such event has been documented till date.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Handling Editor: Dr Adilia Warris