self-learning slides

Madurella mycetomatis: Eumycotic mycetoma

A 33-year old male working as a labourer in a farm presents himself with swollen foot with multiple draining sinuses. On questioning him, he revealed that he had a thorn prick on the same foot few years ago. He recollected that there was a small nodule at the site of thorn prick, which had enlarged progressively. The lesion was painless.

What is your diagnosis?
This could be a case of mycetoma (bacterial or fungal). Other conditions to be considered include actinomycosis, nocardiosis, chromoblastomycosis, botryomycosis, thorn granuloma, fibrolipoma, neurofibroma, necrotizing fasciitis and cold abscess.

What is the specimen collected?
The discharge from the sinuses are collected after cleaning the surface. Along with the discharge, presence of granules (grains/sclerotia) must be looked for and collected. Application of sterile gauze piece over the sinus and application of pressure may squeeze out some discharge. Presence of pus may indicate secondary bacterial infection. A biopsy of the lesion may also be taken.

Which are the necessary investigations to be performed?
A smear must be made from sinus discharge and stained by Gram stain. A KOH mount of the same can also be made. The granules (if present) must be washed in sterile saline. Its size and colour must be noted. It must be crushed between two slides and stained by Gram stain. The specimen must be cultured on Blood agar, Sabourauds dextrose agar without cycloheximide and incubated at room temperature as well as at 37oC. The tissue sections must be stained by H&E, Gomori methenamine silver or periodic acid-Schiff stain.

What is your observation?
Black grains were obtained along with the discharge. The gram stained smear did not reveal any pus cells or organisms. The tissue biopsy revealed grains along the sinus tracts. GMS stained sections reveal thick walled hyphae. The crushed grains revealed broad branching filaments. The culture on SDA produced colonies that were white and woolly at first, becoming olivaceous, yellow, or brown, generally producing a brownish, diffusing pigment. M. mycetomatis assimilates lactose but not sucrose, whereas M grisea assimilates sucrose but not lactose. M. mycetomatis grows well at 37°C, while M. grisea does not grow at 37°C. Colonies are usually sterile and are composed of dense mycelium with melanin pigment. Phialides with minute conidia in short chains and collarettes may be seen very rarely. The microscopic appearances of M. mycetomatis and M. grisea are quite similar. The fungus is identified as Madurella mycetomatis.

Which are the etiological agents of eumycotic mycetoma?
Acremonium falciforme, Acremonium kiliense, Acremonium recifei, Cylindrocarpon cyanescens, Cylindrocarpon destructans, Pseudallescheria boydii, Fusarium oxysoprum, Fusarium solani, Fusarium moniliforme, Aspergillus flavus, Aspergillus nidulans, Polycytella hominis, Curvularia geniculata, Curvularia lunata, Leptosphaeria senegalensis, Madurella grisea, Madurella mycetomatis, Pyrenochaeta romeroi, Exophiala jeanselmei, Phialophora verrucosa

What is the pathogenesis of this condition?
Mycetoma can be caused by actinomycetes (actinomycotic mycetoma) or fungi (eumycotic mycetoma). Even though the etiology differ, the pathogenesis of both these forms are similar. Infection occurs by way of traumatic implantation of the actinomycete or fungus living in soil or vegetation into the tissue. The feet are commonly affected followed by hands, legs and knee joints. In highly endemic areas, other parts of the body might become affected as well. A history of thorn prick may be obtained in some cases, while in others patients' may not recall any such incident. Mycetoma is a chronic granulomatous infection characterized by the triad of tumefaction (swelling), draining sinuses and presence of grains. Grains, also known as sclerotia, are aggregates of the fungal hyphae or the bacterial filaments, sometimes embedded in tough, cement-like material. The morphological characteristics and colour of the grains provides clues about the species of the agents. Infection begins in the subcutaneous tissue after being implanted there and takes a slow progressive course. Incubation period can vary from several months to years. Mycetoma initially presents as a slowly progressive and painless subcutaneous swelling, which is usually firm and rounded but it can also be soft and lobular. The subcutaneous nodule increases in size and secondary nodules might evolve as well. The nodules might suppurate and drain through multiple sinus tracts, and these sinuses can close transiently after discharge during the active phase of the disease. Fresh adjacent sinuses might open whereas some of the old ones might heal completely. The nodules are connected to each other through deep sterile abscesses, and to the skin surface. The lesions are painless except in the end stage where bone invasion may cause pain. As the mycetoma granuloma increases in size, the skin may become smooth and shiny, and areas of hypopigmentation or hyperpigmentation can occur.

How do you treat this condition?
Treatment depends on the correct diagnosis; since treatment for actinomycotic and eumycotic mycetoma is different. Early cases with well-encapsulated lesions without bone involvement can be treated efficiently with surgery. In such cases, combination of medical treatment before and after surgery results in the most successful outcome. Currently, itraconazole and ketoconazole are still the best treatment options.

What are the differences between actinomycotic and eumycotic mycetoma?
Eumycotic mycetoma are caused by several fungi. Some of the characteristic features include well-encapsulated lesions with a clear margin, few sinuses, white or black grains, slow progression of disease, and invasion of bone occurs after a long time. Eumycotic mycetoma may need surgical removal of affected tissue along with treatment with antifungal drugs. Recurrence can occur. Actinomycotic mycetoma are caused by actinomycetes bacteria. Characteristic features include diffuse lesions without clear margin, grains in many colours but not black, course of infection is inflammatory and rapid and rapid invasion of bone occurs. Surgery may not be required in many cases and treatment using antibiotics alone can be sufficient.