Eumycetoma
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Eumycetoma, also known as Madura foot, is a persistent
fungal infection Fungal infection, also known as mycosis, is disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common ti ...
of the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
and the tissues just under the skin, affecting most commonly the feet, although it can occur in hands and other body parts. It starts as a painless wet nodule, which may be present for years before ulceration, swelling, grainy discharge and weeping from
sinuses Paranasal sinuses are a group of four paired air-filled spaces that surround the nasal cavity. The maxillary sinuses are located under the eyes; the frontal sinuses are above the eyes; the ethmoidal sinuses are between the eyes and the spheno ...
and
fistula A fistula (plural: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow or ...
e, followed by bone deformity. Several fungi can cause eumycetoma, including: ''
Madurella mycetomatis ''Madurella mycetomatis'' is a fungus primarily reported in Central Africa as a cause of mycetoma in humans. It has been misclassified for many years, but with improvement of molecular techniques, its phylogenetic classification has been establ ...
'', ''
Madurella grisea ''Madurella grisea'' is a fungal species of the genus ''Madurella''. Along with '' Exophiala jeanselmei'', ''Madurella grisea'' is one of the most common pathogenic agents associated with eumycetoma Eumycetoma, also known as Madura foot, is ...
'', '' Leptosphaeria senegalensis'', ''
Curvularia lunata ''Cochliobolus lunatus'' is a fungal plant pathogen that can cause disease in humans and other animals. The anamorph of this fungus is known as ''Curvularia lunata'', while ''Cochliobolus lunatus'' denotes the teleomorph or sexual state. They ar ...
'', ''
Scedosporium apiospermum ''Pseudallescheria boydii'' is a species of fungus classified in the Ascomycota. It is associated with some forms of eumycetoma/ maduromycosis and is the causative agent of pseudallescheriasis. Typically found in stagnant and polluted water, it ...
'', '' Neotestudina rosatii'', and ''
Acremonium ''Acremonium'' is a genus of fungi in the family Hypocreaceae. It used to be known as ''Cephalosporium''. Description ''Acremonium'' species are usually slow-growing and are initially compact and moist. Their hyphae are fine and hyaline, and pro ...
'' and ''
Fusarium ''Fusarium'' is a large genus of filamentous fungi, part of a group often referred to as hyphomycetes, widely distributed in soil and associated with plants. Most species are harmless saprobes, and are relatively abundant members of the soil mi ...
'' species. Diagnosis is by
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
, visualising the fungi under the microscope and
culture Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups ...
.
Medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to re ...
may reveal extent of bone involvement. Other tests include
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
,
immunodiffusion Immunodiffusion is a diagnostic test which involves diffusion through a substance such as agar Agar ( or ), or agar-agar, is a jelly-like substance consisting of polysaccharides obtained from the cell walls of some species of red algae, prim ...
, and
DNA Barcoding DNA barcoding is a method of species identification using a short section of DNA from a specific gene or genes. The premise of DNA barcoding is that by comparison with a reference library of such DNA sections (also called " sequences"), an indi ...
. Treatment includes surgical removal of affected tissue and antifungal medicines. After treatment, recurrence is common. Sometimes, amputation is required. The infection occurs generally in the tropics, and is endemic in Sub-Saharan Africa, especially Sudan, India, parts of South America and Mexico. Few cases have been reported across North African. Mycetoma is probably low-endemic to Egypt with predilection for eumycetoma. In 2016, the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
recognised eumycetoma as a
neglected tropical disease Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bac ...
.


Signs and symptoms

The initial lesion is a small swelling under the skin following minor trauma. It appears as a painless wet nodule, which may be present for years before ulceration, swelling and weeping from
sinuses Paranasal sinuses are a group of four paired air-filled spaces that surround the nasal cavity. The maxillary sinuses are located under the eyes; the frontal sinuses are above the eyes; the ethmoidal sinuses are between the eyes and the spheno ...
, followed by bone deformity. The sinuses discharge a grainy liquid of fungal colonies. These grains are usually black or white. Destruction of deeper tissues, and deformity and loss of function in the affected limbs may occur in later stages. It tends to occur in one foot. Mycetoma due to bacteria has similar clinical features.


Causes

Eumycetoma is a type of
mycetoma Mycetoma is a chronic infection in the skin caused by either bacteria (actinomycetoma) or fungi (eumycetoma), typically resulting in a triad of painless firm skin lumps, the formation of weeping sinuses, and a discharge that contains grains. 80% ...
caused by fungi. Mycetoma caused by bacteria from the phylum
Actinomycetes The Actinomycetales is an order of Actinomycetota. A member of the order is often called an actinomycete. Actinomycetales are generally gram-positive and anaerobic and have mycelia in a filamentous and branching growth pattern. Some actinomycete ...
is different. Both have similar clinical features. The most common fungi causing white discharge is ''
Pseudallescheria boydii ''Pseudallescheria boydii'' is a species of fungus classified in the Ascomycota. It is associated with some forms of eumycetoma/ maduromycosis and is the causative agent of pseudallescheriasis. Typically found in stagnant and polluted water, it ...
''. Other causative agents of non-black grain eumycetoma include ''
Acremonium ''Acremonium'' is a genus of fungi in the family Hypocreaceae. It used to be known as ''Cephalosporium''. Description ''Acremonium'' species are usually slow-growing and are initially compact and moist. Their hyphae are fine and hyaline, and pro ...
'' and ''
Fusarium ''Fusarium'' is a large genus of filamentous fungi, part of a group often referred to as hyphomycetes, widely distributed in soil and associated with plants. Most species are harmless saprobes, and are relatively abundant members of the soil mi ...
'' species. Black discharge tends to be caused by species from the genera ''
Madurella ''Madurella'' is a fungal genus of Hyphomycetes, of uncertain position in the Sordariales, and sometimes classified as Mitosporic Ascomycota. It includes: * '' Madurella grisea'' * ''Madurella mycetomatis'' ''Madurella mycetomatis'' is a mai ...
'', ''
Pyrenochaeta Pyrenochaeta is a genus of fungus. It includes the species '' Pyrenochaeta romeroi''. Can cause a disease called eumycetoma Eumycetoma, also known as Madura foot, is a persistent fungal infection of the skin and the tissues just under the ...
'', '' Exophiala'', '' Leptosphaeria'' and ''
Curvularia ''Curvularia'' is a genus of hyphomycete (mold) fungi which can be pathogens but also act as beneficial partners of many plant species. They are common in soil. Most ''Curvularia'' species are found in tropical regions, though a few are found in ...
''. The most common species are ''
Madurella mycetomatis ''Madurella mycetomatis'' is a fungus primarily reported in Central Africa as a cause of mycetoma in humans. It has been misclassified for many years, but with improvement of molecular techniques, its phylogenetic classification has been establ ...
'' and '' Trematospheria grisea'' (previously called ''
Madurella grisea ''Madurella grisea'' is a fungal species of the genus ''Madurella''. Along with '' Exophiala jeanselmei'', ''Madurella grisea'' is one of the most common pathogenic agents associated with eumycetoma Eumycetoma, also known as Madura foot, is ...
'').


Mechanism

The disease is acquired by entry of the fungal
spore In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, ...
s from the soil through a breach in the skin produced by minor trauma like a thorn prick. The disease then spreads to deeper tissues and also forms sinus tracts leading to skin surface. Mature lesions are characterised by a grainy discharge from these sinuses. These discharges contain fungal colonies and are infective. Spread of infection internally through blood or
lymph Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues ...
is uncommon. Infections that produce a black discharge mainly spread subcutaneously. In the red and yellow varieties deep spread occurs early, infiltrating muscles and bones but sparing nerves and tendons, which are highly resistant to the invasion.Hamilton Bailey's ''Demonstrations of Physical Signs in Clinical Surgery''
Botryomycosis Botryomycosis is a bacterial skin infection that typically presents with crusted, purulent large bumps. Sulphur granules generally discharge via sinuses, which heal leaving thin skinned scars. Presentation Associated conditions There are only a ...
, also known as bacterial pseudomycosis, produces a similar clinical picture and is caused usually by ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posit ...
''. Other bacteria may also cause botryomycosis.


Diagnosis

Diagnosis is by
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
, visualising the fungi under the microscope and
culture Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups ...
, which show characteristic fungal filaments and vesicles characteristic of the fungi. Other tests include
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
,
immunodiffusion Immunodiffusion is a diagnostic test which involves diffusion through a substance such as agar Agar ( or ), or agar-agar, is a jelly-like substance consisting of polysaccharides obtained from the cell walls of some species of red algae, prim ...
, and PCR with
DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. T ...
(so-called
DNA barcoding DNA barcoding is a method of species identification using a short section of DNA from a specific gene or genes. The premise of DNA barcoding is that by comparison with a reference library of such DNA sections (also called " sequences"), an indi ...
).
X rays An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10  picometers to 10 nanometers, corresponding to frequencies in the range 30  ...
and ultrasonography may be carried out to assess the extent of the disease. X rays findings are extremely variable. The disease is most often observed at an advanced stage that exhibits extensive destruction of all bones of the foot. Rarely, a single lesion may be seen in the tibia where the picture is identical with chronic osteomyelitis.
Cytology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...
of fine needle aspirate or pus from the lesion, and tissue
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
may be undertaken sometimes. Some publications have claimed a "dot in a circle sign" as a characteristic MRI feature for this condition (this feature has also been described on ultrasound).


Differential diagnosis

The following clinical conditions may be considered before diagnosing a patient with mycetoma: #
Tuberculous ulcer Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, i ...
# Kaposi's sarcoma, a vascular tumour of skin usually seen in AIDS. # Leprosy # Syphilis # Malignant neoplasm #
Tropical ulcer Tropical ulcer, more commonly known as jungle rot, is a chronic ulcerative skin lesion thought to be caused by polymicrobial infection with a variety of microorganisms, including mycobacteria. It is common in tropical climates. Ulcers occur on ...
#
Botryomycosis Botryomycosis is a bacterial skin infection that typically presents with crusted, purulent large bumps. Sulphur granules generally discharge via sinuses, which heal leaving thin skinned scars. Presentation Associated conditions There are only a ...
, a skin infection usually caused by the bacteria
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posit ...
.


Prevention

No vaccine is available. Simple hygienic precautions like wearing shoes or sandals while working in fields, and washing hands and feet at regular intervals may help prevent the disease.


Treatment

Surgery combined with
itraconazole Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mo ...
may be given for up to year when the grains are black.
Posaconazole Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication. It was approved for medical use in the United States in September 2006, and is available as a generic medication. Medical uses Posaconazole is u ...
is another option.
Voriconazole Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by ' ...
can be used for infections caused by ''Fusarium'' species.
Ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...
has been used to treat eumycetoma but has many side effects.
Actinomycetes The Actinomycetales is an order of Actinomycetota. A member of the order is often called an actinomycete. Actinomycetales are generally gram-positive and anaerobic and have mycelia in a filamentous and branching growth pattern. Some actinomycete ...
usually respond well to medical treatment, but eukaryotic infections are generally resistant and may require surgical interventions including salvage procedures as bone resection or even the more radical amputation.


Epidemiology

The disease is more common in males aged 20–40 years who work as labourers, farmers and herders, and in travellers to tropical regions, where the condition is endemic.


History

Madura foot or maduromycosis or maduramycosis is described in ancient writings of India as ''Padavalmika'', which, translated means ''Foot anthill''. The first modern description of Madura foot was made in 1842 from
Madurai Madurai ( , also , ) is a major city in the Indian state of Tamil Nadu. It is the cultural capital of Tamil Nadu and the administrative headquarters of Madurai District. As of the 2011 census, it was the third largest Urban agglomeration i ...
(the city after which the disease was named ''Madura''-mycosis) in India, by Gill. The fungal cause of the disease was established in 1860 by Carter.


Society and culture

In 2016, the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
recognised eumycetoma as a
neglected tropical disease Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bac ...
. Traditionally occurring in regions where resources are scarce, medicines may be expensive and diagnosis is frequently made late, when more invasive treatment may be required.


References


External links

{{Mycoses Tropical diseases Mycosis-related cutaneous conditions Fungal diseases Neglected American diseases