Successful Management of Rhinofacial Conidiobolus coronatus Infection with Itraconazole Monotherapy

ABSTRACT.

There are no standard guidelines on the management of Conidiobolus infections, and many antifungals have been used, either alone or in combination. Relapses are common even after successful management. Although localized, they can result in severe facial disfigurement and may rarely cause disseminated entomophthoromycosis, which can have fatal complications. We present a case of biopsy-proven conidiobolomycosis in a young immunocompetent male patient with progressive unilateral rhinofacial swelling who was successfully treated with itraconazole monotherapy and showed no relapse after 1 year of therapy.

INTRODUCTION

Rhinofacial entomophthoromycosis is an uncommon chronic subcutaneous mycoses caused by Conidiobolus species, reported mainly from tropical and subtropical countries. It most frequently manifests as a localized, painless, subcutaneous swelling over rhinofacial areas; however, disseminated forms have been reported in both immunocompetent and immunocompromised patients.¹ A high index of suspicion is required to avoid delay in the diagnosis and management of these cases.

CASE REPORT

A 17-year-old immunocompetent male presented to us with redness and asymmetrical swelling over the nose and left cheek and a pinkish fleshy mass in the left nasal cavity causing nasal blockage for the past 6 months. There were no additional neurological or ophthalmological complaints. There was no history of trauma prior to the onset of these lesions. Clinical examination revealed a nonbleeding polypoidal mass in the left nasal cavity and an ill-defined indurated erythematous plaque over the nose and left cheek (Figure 1A and B). The patient was investigated, keeping the differential diagnoses of subcutaneous mycoses, sarcoidosis, borderline tuberculoid leprosy, lupus vulgaris, and granuloma faciale.

Figure 1.

(A) A 17-year-old male presented with erythematous indurated plaque over the nose and left cheek. (B) Polypoidal mass in the left nasal cavity for 6 months. (C) Complete resolution of cutaneous and nasal mucosal lesions after 5 months of itraconazole monotherapy.

Routine hematological and biochemical investigations were within normal limits. Viral markers (Hepatitis B surface Antigen, Hepatitis C virus antibodies, and Human Immunodeficiency Virus) and a detailed workup for tuberculosis were negative. Computed tomography of the paranasal sinuses showed a soft-tissue mass in the left nose with no bony erosion. Histopathological examination of the mass in the nasal cavity obtained through sublabial approach revealed fibromuscular and fibrocollagenous tissue with a dense mixed inflammatory infiltrate consisting of neutrophils, lymphocytes, eosinophils, histiocytes, giant cells, and ill-formed epithelioid cell granulomas (Figure 2A). Palisading histiocytes surrounding necrosis, adorned with broad-based pauci-septate hyphae, were also distinctly observed (Figure 2B). Periodic acid-Schiff and Gomori methanamine silver stain confirmed the presence of these hyphae embedded in the necrotic tissue (Figure 2C and D). Gram stain for bacteria and Zeihl-Neelsen stain for acid-fast bacilli yielded negative results.

Figure 2.

(A) Biopsy from the mass in the nasal cavity showing fibrocollagenous tissue with a dense mixed inflammatory infiltrate and ill-formed epithelioid cell granulomas (black arrow) (H&E, 200×). (B) Palisading histiocytes surrounding necrosis along with broad-based pauci-septate hyphae (H&E, 400×). Pauci-septate hyphae embedded in necrotic tissue highlighted on (C) Gomori methanamine silver stain (400×) and (D) periodic acid-Schiff stain (400×). H&E = Hematoxylin and Eosin.

Fungal culture from the tissue on Sabourad dextrose agar media with chloramphenicol showed growth of Conidiobolus coronatus species. A final diagnosis of rhinofacial conidiobolomycosis was made, and the patient was started on oral itraconazole 200 mg twice daily, resulting in complete resolution of the cutaneous and nasal lesions within 5 months (Figure 1C). The drug was continued for a total period of 6 months, and no side effects were noted. The patient continues to be under follow-up and has been in remission for the past 1 year after stopping the treatment.

DISCUSSION

Conidiobolomycosis is an extremely rare, invasive, subcutaneous mycosis caused by C. coronatus (order Entomophthorales) and prevails in tropical regions of Asia, Africa, and America.² Young and middle-aged men are more predisposed to the infection, and it is rarely encountered in children.^3,4 The proposed mode of infection is either by inhalation of mold spores or via direct inoculation into the nasal mucosa that subsequently spreads to the adjacent subcutaneous tissue.⁵ It most commonly involves the upper respiratory tract, including the nose and paranasal sinuses of immunocompetent individuals.

Invasive pulmonary infections due to Conidiobolus pachyzygosporus, rhino-orbitocerebral entomophthoromycosis due to Conidiobolus incongruous, and disseminated infections due to Conidiobolus lamprauges have been reported in immunocompromised patients with onco-hematological malignancies.^6–8 Rhinofacial conidiobolomycosis commonly presents as nasal obstruction, followed by rhinofacial swelling, epistaxis, chronic sinusitis, throat pain, and epiphora.⁹ Rarely, it can lead to inferior turbinate granuloma formation^10,11 and extensive involvement of the pharynx or larynx presenting as dysphagia or laryngeal obstruction.¹²

The diagnosis remains a challenge for the clinician because of the rarity of the disease, more so in the Indian subcontinent, alteration of the initial clinical morphology, and involvement of ocular and cerebral tissue. The mainstay of diagnosis is the histopathological examination and a fungal culture of the tissue obtained by incisional biopsy by the sublabial approach.³

Histopathological examination characteristically shows a granulomatous tissue reaction composed of epithelioid cell granulomas, foamy histiocytes, mixed inflammatory infiltrates of lymphocytes, and eosinophils admixed with necrotic tissue, as well as the Splendore Hoeppli phenomenon in some cases. Fungal hyphae can be better visualized using special stains such as Gomori methanamine silver stain, where black fungal hyphae are seen against a green necrotic background, and periodic acid-Schiff stain, where the fungal hyphae are highlighted within the tissue. Fungal culture delineates the species from less invasive C. coronatus to highly invasive C. pachyzygosporus, C. lamprauges, or C. incongruous.

Medical management forms the cornerstone of therapy. Surgical excision is avoided as it may hasten the spread of infection,¹³ but surgical debridement has been reported to be successful in few patients. There is no single antifungal agent with consistent antifungal activity against conidiobolomycosis, and the drugs used include supersaturated solution of potassium iodide (SSKI), itraconazole, terbinafine, cotrimoxazole, and rarely, amphotericin B, ketoconazole, or fluconazole, either as monotherapy or in combination with other medical or surgical modalities for an average of 6 months.¹⁴ In most cases, SSKI and itraconazole have been used as first-line drugs. Treatment should be continued for at least 1 month after the lesions have cleared or until cultures are negative.

There have been rare reports of use of itraconazole as the sole medical management therapy for a period of 9–18 months but all in adjunct to endoscopic surgical wide resection^15,16 and none as monotherapy. Conidiobolus species have shown high minimum inhibitory concentration (MIC) values for azoles (itraconazole, voriconazole, and posaconazole) as well as amphotericin B (≥16 µg/mL), whereas co-trimoxazole showed much lower MIC values (0.19–0.25 µg/mL)^3,17; however, the correlation between the antifungal susceptibility data and clinical outcome has not been established yet. Despite the higher MIC value of itraconazole to Conidiobolus species,³ our patient responded very well to itraconazole monotherapy within 6 months, with no clinical signs of relapse 12 months after treatment completion.

Rhinofacial conidiobolomycosis poses a rare clinicopathological and therapeutic challenge that necessitates a heightened index of suspicion and early diagnostic interventions in adults with a progressive nasal mass and nasal swelling. This case underscores the uncommon presentation of a subcutaneous mycoses in the Indian subcontinent that responded favorably to itraconazole monotherapy, exhibiting no signs of clinical relapse. The successful outcome prompts a reevaluation of therapeutic approaches for conidiobolomycosis, emphasizing the potential effectiveness of itraconazole as a standalone treatment.