Clinical Services

 

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Outreach Villages Based Clinical Services

Many patients tend to present late with advanced disease where amputation of the affected part may be the only possible treatment. Most of these patients are from under-developed communities, and hence one of the important functions of the MRC is to reach these patients in their own villages and to provide them with free medical and surgical treatment as well as health educations

To execute this, the centre had conducted many field trips to endemic areas where health education sessions were organised, out-patient clinics were conducted, patients were treated using mobile surgical units and team free of charge. Some patients were referred to MRC or specialisedcentres for further management.

 

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The MRC has an out-patient clinic, conducted every Monday morning where patients are seen regularly for treatment and follow up. Health education sessions organized by health workers are conducted regularly. Patients’ counseling is done by the MRC Social workers. The clinic accepts patients from different part of the country and the region as well.

 

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Mycetoma Pathology

Prof. A.M. EL Hassan. MRCP, MRCPath, PhD, DCP
Emeritus Professor of Pathology.
Mycetoma Research Group.
Institute of Endemic Diseases.
University of Khartoum.
E.mail:

 

Mycetoma (maduromycosis) is a chronic granulomatous subcutaneous infection caused by actinomycetes (actinomycetoma) or by true fungi (eumycetoma). Clinically the disease is characterized by swelling, deformity and sinuses in the affected part (Fig.1). Another characteristic feature of mycetoma is the formation of aggregates of the organism (grains) in the tissues, which are visible to the naked eye and are discharged through sinuses in the skin (Fig. 2). The grains vary in colour, size and consistency depending on the causative agent. These features are helpful in making a tentative diagnosis of the causative organism. A definitive identification of the agent is established by the histological examination of the grains, by culture or by serologic techniques.  Both actinomycetoma and eumycetoma prevail in the Sudan. Eumycetoma due to Madurella mycetomatis is the commonest type. The actinomycetoma is commonly caused by Streptomyces somaliensis, Actinomadura madurae and Actinomadura pelletierii.

This, article describes the pathology of the commonest types of mycetomata in the Sudan in surgical material referred to the Pathology Department, Faculty of Medicine, University of Khartoum.

1.  M.  mycotomatis

It is the most common cause of eumycetoma in the Sudan. In clinical material, the grains in the tissue are black and numerous (Fig.3). In stained sections the grain is rounded, oval or trilobed. It has a more compact cortex, which is dark brown in colour due to pigment produced by the organism and has a lighter medulla. In some grains the division into cortex and medulla is not evident. The grain filaments are usually embedded in a hard brown cement matrix.

Two main morphological types of grains are identified. The filamentous, which is the commonest type, consists of brown septate and branched hyphae that may be slightly more swollen towards the periphery (Fig. 4). In the cortex, the filaments are arranged radially while in the medulla they tend to run multi-directionally. Round or oval cells, 7-15 um in diameter, are seen, particularly in the periphery.

The second type of grain is the vesicular one (Fig. 5). It is less common than the filamentous and is composed of unusually large cells that look like vesicles. Both types of the grain can be found in the same lesion. Grains that are partially vesicular and partially filamentous are not uncommonly seen.

The surface of the grain may be scalloped giving the periphery a hob-nail appearance and a brightly eosinophilic layer of fibrin–like material sometimes covers the grain (Fig. 6). This layer is of host origin, contains fibrin, immunoglobulins and complement. A similar material is seen around parasites as Hoepple phenomenon. Occasionally a thin layer of a haematoxophilic granular material is found on the surface of the grain. This material is Feulgen positive and is derived from the nuclei of disintegrating inflammatory cells surrounding the grains. The inflammatory cellular reaction around the grain is variable. There are three types of tissue reaction. In type I, there is a zone of neutrophils in the vicinity of the grain (Figs. 7,8). These are sometimes found within the grain substance causing its disintegration. Some histocytes may also be seen among the neutrophils but they are more numerous outside the neutrophil zone. Some of the histocytes have a foamy cytoplasm and give a positive reaction for fat and stain positive for CD 68 antigen (Figs.9,10). Capillaries, which are sometimes abundant, surround the neutrophil/ histiocyte zone and they are occasionally, surrounded by a layer of fibrin. Lymphocytes, plasma cells, fibroblasts and some macrophages are usually seen in this vascular zone. The lymphocytes and plasma cells increase in number towards the investing fibrous tissue in the periphery of the lesion.

In type II reaction, the neutrophils largely disappear and are replaced by histocytes and multinucleated giant cells (Fig 11). Some of the latter contain fragments of grain or pigmented cement substance without any hyphae. The macrophages may contain a black pigment derived from the grain (Fig. 12). At this stage the grain itself is usually small and fragmented. This type of histocytes/giant cell reaction follows on the earlier neutrophil response, which causes fragmentation of the grain.

In the third type of reaction (Type III), the grain material has largely or completely disappeared leaving a compact epithelioid granuloma with or without langerhans giant cells (Figs.13, 14). This however, is an uncommon reaction but represents spontaneous regression in some grains.

The three types of tissue reaction may be found in the same lesion. Viable grains are nearly always present in biopsy material. It is not known if spontaneous regression of all the grain ever occurs in mycetoma. The unique feature of M. mycetomatis is the formation of a capsule around the lesion. The lesion grows by expansile growth in the tissue plains. In the bones there is usually no capsule formation, the organism usually forming cavities that are filled with the grains. This gives the bone support and may explain the rarity of pathological fractures in mycetoma.

Ultrastructurally the hyphal elements are spherical to elongated and are embedded in grain matrix (Fig. 15). The hyphae are septate, the cytoplasm may be densely ribosomal or disorganized. Some hyphae appear empty, being devoid of cytoplasm. Cytoplasmic organelles such as nuclei and mitochondria are not usually seen. Intra–hyphal re-growth is sometimes seen. The hyphal wall is often markedly thickened. This feature may be involved in the transformation of the fungus to the pathogenic state.

The pigmented substance surrounding the hyphae consists of amorphous electron-dense material and vesicles. The nature of the pigment is not known with certainty. Histologically it resembles melanin and it may be a fungus product. Sclerosis and melanization of the host tissue is, in some manner, responsible for the formation of the cement substance.

Ultrastructural studies of the host reaction show neutrophils adherent to the grain (Figs.16,17,18). The cytoplasm of the neutrophil is stretched over the grain and the neutrophils granules are concentrated in the part of the cytoplasm adjacent to the grain. This is an immune adherence, which is mediated by immunoglobulins and is an example of antibody dependent cell mediated cytotoxicity. Immunoglobulin and complement can be demonstrated in the grain (Figs.19, 20).

Bones are frequently involved in advanced mycetoma of the soft tissue (Figs. 21,22,23). Occasionally primary bone mycetoma in the absence of soft tissue involvement is seen. M. mycetomatis produces lytic lesions which are  large in size, few in number and have well defined margins; this is well seen radiologically.

   

2. Streptomyces somaliensis:

The grains are yellow in colour and hard in consistency. During surgery it may be difficult to distinguish the grains from fat which makes radical excision of the lesion difficult. This is especially so since the lesion is not encapsulated. In sections the grain is rounded to oval, dense and homogenous. Characteristically marks of the microtome knife are seen in the grain in the form of parallel cracks. The grain stains a light purple or pink colour in haematoxylin and eosin stained sections (Fig 7). The grain varies in size from 30 to 200 um. Hyphal elements embedded in cement can be visualized by Gram stain.

The grain is surrounded by an intense neutrophil polymorphonuclear leucocyte infiltrate (Type 1). Outside this zone, there is a vascular layer containing macrophage, lymphocytes, plasma cells and giant cells. The giant cells usually contain fragments of the grain. Some macrophages have a foamy cytoplasm. It looks as though the fragmentation of the grain induced by neutrophils is less severe than in M. mycetomatis. This may be due to the more compact and hard grains of S. somaliensis. Small grains surrounded by macrophages and giant cells (Type 11) are occasionally seen but pure epithelioid granuloma (Type 111) apparently does not occur. Giant cells containing viable actinomycetes are believed to aid the spread of the organism in the tissue and to the regional lymph nodes. Despite the invasive nature of S. somaliensis and other actinomycetes, tendons and nerves are resistant to invasion.

Ultrastrcturally the grain consists of heterogenous and amorphous matrix arranged in an irregular and reticulate structure surrounding electron lucent areas between 1 and 5 um. In some of these spaces bacterial filament are found. The organisms are usually unicellular and coccoid and the cell wall is electron dense.

   

3. Actinomadura pelletierii:

The grains in clinical material are tiny and red in colour (Fig. 24). In section the grain is rounded, oval or semilunar. It stains a purple colour and compact hyphae give it the appearance of “Iron filings”. The periphery of the grain has a narrow deeply eosinophilic band. The grain is usually surrounded by a zone of neutrophils which causes fragmentation of the grain. The other layers are similar to those seen in S. somaliensis but the giant cells are less conspicuous.

The ultrastructure of the grain is quite distinctive. The hyphae are septate, compact without cement substance and under low magnification the hyphae have a starry sky appearance because of the vacuoles in the hyphae. These are probably fixation artifacts. Neutrophils usually adhere to the grain and degranulate. Grain material is phagocytosed by the neutrophils and destroyed.

4. Actinomadura madurae:

Macroscopically the grains are yellow or white. They are difficult to distinguish from the surrounding fat. Histologically the large grains have a characteristic variegated pattern (Fig. 25). The periphery of the grain is dense, homogenous and deep purple while the centre is less dense or even appears hollow. Not infrequently the grain fragments into geometric fragments. The periphery shows a brightly eosinophilic material forming clubs. This, material contains immunoglobulins. Smaller grains are more homogeneous and are difficult to distinguish from A. pelletierii.

However, even the small grains of A. madurae have a more deeply stained purple fringe, which is not seen in A. pelletierii. The inflammatory reaction is similar to that of A. pelletierii.

5.  Vascular changes in mycetoma

The arteries and veins in the mycetoma lesion show hypertrophy of the muscles (Fig. 26). The lumen is narrowed but is not occluded completely. Grain fragments are occasionally seen within the blood vessels. These may explain the rare haematogenous spread to distant sites.

6. Cytopathology of mycetoma

Fine needle aspiration cytology of mycetoma was described. Mycetoma has  distinct cytological features characterized by the presence of polymorphous inflammatory cells consisting of neutrophils, lymphocytes, plasma cells, histocytes and foreign body giant cells. The causative organism is identified in most of the cases, surrounded or/ and infiltrated by neutrophils. M. mycetomatis grains are rounded or oval in shape. In Giemsa stained smears, they appear black with green tinge of colour and brownish in H&E.  Two types of M. mycetomatis grains could be identified in cytological smears, the solid granular one, which is the commonest and the vesicular. The septate hyphae are not identified in the first type as they are embedded in a hard brown cement matrix. The vesicular type consists of swollen fungal cells, seen as vesicles.

Actinomycetes grains are homogeneously eosinophilic in H&E (Fig. 27). In Geimsa stained smears the grain appears homogeneously blue in the center while in the periphery it consists of fine granules and radiating pink filaments.

The A. pelletieri grain is more eosinophilic in H&E as compared to S. somaliensis and it is semilunar in shape as seen in histology. To distinguish between actinomycetoma and eumycetoma, fine needle aspiration cytology was found to be as accurate as histopathology when grains are present. The cytological features of mycetoma correlates well with the histologic one.

The technique is simple, quick and cheap. It can be introduced for routine diagnosis of mycetoma and for epidemioloical surveys and for sample collection for culture.

7.  Bony changes in mycetoma:

 Bones are frequently involved in advanced mycetoma of the soft tissue. Occasionally primary bone mycetoma in the absence of soft tissue involvement is seen. M. mycetomatis produces lytic lesions which are  large in size, few in number and have well defined margins.

Actinomycetoma destroys bone and also evokes new bone formation. The cavities produced are usually smaller in size, numerous and have no definite margins.  A periosteal reaction with new bone formation and sun-ray appearance may be seen in radiographs. This features along with Codaman’s triangle simulates the radiographic changes in osteogenic sarcoma.

8.  Lymph nodes in mycetoma:

Lymph nodes draining a mycetoma focus are frequently enlarged. Most of the node shows only reactive hyperplasia with an intense plasma cell infiltration. The plasma cells often contain Russell bodies. These changes may be due to antigens reaching the node from grains at the primary site. Secondary bacterial infection of the mycetoma lesion may also be a factor. Occasionally the organism metastasizes to the nodes causing lymphadenitis with sinuses discharging grains (Fig. 28). This is more frequent with actinomycetoma than with eumycetoma. Not infrequently haemosiderin deposits are found in the nodes even in the absence of grains. The haemosiderin is derived from the granulation tissue in the peripheral lesion draining into the lymph nodes. Melanin is also found in the node and may be confused with the pigment of M. mycetomatis.

Further reading:

1.      EL Hassan AM, Fahal AH, EL Hag IA, Khalil EAG, The pathology of mycetoma: Light microscopic and ultrastructural features. Sudan Medical Jorunal. 1994; 32: 23-45.  

2.      Fahal AH, EL Toum EA, EL Hassan AM, Gumaa SA, Mahgoub ES, A preliminary study on the ultrastructure of Actinomadura pelletierii and its host tissue reaction. Journal of Medical and veterinary Mycology 1994; 32: 343-348.

3.      Mahgoub ES and Murray TG.  Mycetoma William Heineman, Medical Books, London.

4.      Fahal AH, EL Toum EA, EL Hassan AM, Gumaa SA, Mahgoub ES, Host tissue reaction to Madurella mycetomatis: New classification. Journal of Medical and veterinary Mycology. 1995; 33: 15-17.  

5.      EL Hag IA, Fahal AH, Khalil EAG, Fine needle aspiration cytology of mycetoma.   Acta Cytologica. 1996; 40(3): 461-464.  

6.      Fahal AH, EL Hag IA, Gadir AFA, EL Lider AR, EL Hassan AM, The blood supply and vasculature in mycetoma. Journal of Medical and veterinary Mycology. 1997;  35:101-106.

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Interesting Cases

Rare presentation of actinomycetoma

Case Report
A.H. Fahal and H. E. Sheik
Mycetoma Research Centre,
University of Khartoum,
Khartoum-Sudan

The patients; is a 36 year-old gentleman, farmer from Western Sudan. He presented to the Mycetoma Clinic at Soba University Hospital, Khartoum, Sudan with massive swelling of the left side of the back extending down to the gluteal region. The condition stared 18 years with a small painless swelling in the left lower part of his back at a site of trauma following a fall from a tree. It then gradually regressed in size. Two year later the swelling gradually stared to increase in size, sinuses discharging yellow grains then developed. He had no past history of bilharziasis or haematemesis. His social, family or drug history is not contributory to his condition.

On examination he looks unwell and slightly pale. Head and neck, chest and cardio-vascular, central nervous system examination are within normal. He has gynaecomastia of the left breast, which is tender and firm in consistency. Abdominal examination revealed multiple distended veins extending from the left hypochondrial region to the left iliac fossa. The spleen is grossly enlarged otherwise normal clinical findings.

Local examination of the back revealed huge mass involving the whole left side of back extending to the chest wall and down to the gluteal region. The mass was painless, firm in consistency with areas of hypopigmentation. The skin was tethered to the deep structures with multiple healed sinuses.

His full blood count and ESR are within normal. Abdominal ultrasound showed an enlarged spleen with normal texture, normal splenic vein and evidence of bilharzial periportal fibrosis. Intravenous urography showed normal function of both kidneys, the left ureter was deviated medically and erosion of the left 12 rib and the first five lumber vertebrae.  Abdominal CT scan showed a huge mass at the back pushing the left kidney and ureter medical with erosion of the first five lumber vertebrae. An incisional biopsy was taken under local anesthesia and it confirmed the diagnosis of actinomycetoma due to Streptomyces somaliensis. MRI examination showed huge soft tissue mass.

The patient was stared on streptomycin sulphate in a dose of 14 mg/kg daily for one month then on alternate days and diaminodiphenyl sulphone (dapsone) in a dose of 1.5 mg/kg twice daily and Co-trimoxazole in a dose of 14 mg/kg twice daily. His portal hypertension was treated conservatively.  At two months follow up he showed dramatic clinical improvement the mass had regressed in size, sinuses had healed and the skin became less tethered to the underline tissue.

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Review Article

Professor A. H. Fahal, MBBS, FRCS,FRCSI,FRCSG, MD, MS, FRCP(London)
Professor of Surgery
Mycetoma Research Centre
University of Khartoum
E.mail:           

                                       
Introduction
Epidemiology and Aetiology
The causative organisms
Clinical presentation
Site of mycetoma
Differential diagnosis
Diagnosis of mycetoma
Radiology
Management
Eumycetoma Medical Treatment
Treatment of actinomycetoma
Surgery for mycetoma
References
 

Introduction:

Mycetoma is a chronic, specific, granulomatous, progressive inflammatory disease; it usually involves the subcutaneous tissue after a traumatic inoculation of the causative organism. Mycetoma may be caused by true fungi or by higher bacteria and hence it is usually classified into eumycetoma and actinomycetoma respectively (1).  Tumefaction and formation of sinus tracts characterize mycetoma. The sinuses usually discharge purulent and seropurulent exudate containing grains. It may spread to involve the skin and the deep structures resulting in destruction, deformity and loss of function, very occasionally it could be fatal (2,3).
         

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Epidemiology :

The true incidence and the geographical distribution of mycetoma throughout the world is not exactly known due to the nature of the disease which is usually painless, slowly progressive which may lead to the late presentation of the majority of patients. Mycetoma has a worldwide distribution but this is extremely uneven. It is endemic in tropical and subtropical regions. The African continent seems to have the highest prevalence (4).  It prevails in what is known as the mycetoma belt stretching between the latitudes of 15 south and 30 north (5). The belt includes Sudan, Somalia, Senegal, India, Yemen, Mexico, Venezuela, Columbia, Argentina and others.

The geographical distribution of the individual mycetoma organism shows considerable variations, which can be convincingly explained on an environmental basis. Areas where mycetoma prevails are relatively arid zones with a short rainy season with a relative humidity.

The organisms are usually present in the soil in the form of grains. The infecting agent is implanted into the host tissue through a breach in the skin produced by trauma caused by sharp objects such as thorn pricks, stone or splinters.
 

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The Causative Organisms:

A variety of eumycetes and actinomycetes are incriminated in the causation of mycetoma. Not less than 18 organisms have were reported from different parts of the world  (Table)

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Clinical Presentation:

Male predominance is a constant finding in mycetoma with a sex ratio of 3.7:1. This is commonly attributed to the greater risk of exposure to organisms in the soil during the outdoor activities. No age is exempted but mycetoma commonly affects adults between 20-40 years of age and these are the earning members of the society especially in under developed countries.  However, in endemic regions children and elderly people may also be affected (3,5). Mycetoma is seen more conventionally in cultivators, field laborers and in herdsmen who come in contact with the land in endemic areas people of other occupations are affected.

The clinical presentation of mycetoma is almost identical irrespective of the causal organism. However, the rate of progress is more rapid with actinomycetoma than with eumycetoma. In eumycetoma, the lesion grows slowly with clear defined margins and remains encapsulated for a long period, whereas, in actinomycetoma the lesion is more inflammatory, more destructive and invades the bone at an earlier period (1,5). The characteristic triad, of a subcutaneous mass, sinus and the presence of discharge containing grains are pathognomic of mycetoma. It presents as a slowly progressive painless subcutaneous swelling at the site of previous trauma. The swelling is usually firm and rounded but it may be soft, lobulated, rarely cystic and it is often mobile. Multiple secondary nodules then evolve as well, the nodules may suppurate and drain through multiple sinus tracts and these sinuses may close transiently after discharge during the active phase of the disease. Fresh adjacent sinuses may open while some of the old ones may heal completely. They are connected with each other, with deep sterile abscesses and with the skin surface. The discharge is usually serous, serosanguinous or purulent. During the active phase of the disease the sinuses discharge grains (fungal colonies) the colour of which depends on the causative organism. The grains can be black, yellow, white or red and they are of variable size and consistency. The black grains are usually due to M. mycetomatis, the red ones are due to A. pelletierii and the white grains can be due to A. madurae. Pus, exudate, the dressing gauze and biopsy material should be examined for the presence of the grains (Fig 1,2).

Mycetoma is usually painless in nature, it was suggested that the mycetoma produces substances that have an anaesthetic action (3). At a late stage of the disease the pain may become negligible due to nerve damage by the tense fibrous tissue reaction, endarteritis obliterans or poor vascularisation of the nerve (3). Pain may be produced by the expansion of the bone with the mycetoma granuloma and grains or it may be due to secondary bacterial infection (6).

As the mycetoma granuloma increases in size the skin over it becomes attached and stretched. The skin may become smooth, shiny and areas of hypo or hyper-pigmentation may develop. In some of the mycetoma patients there may be areas of local hyperhidrosis confined only to the mycetoma lesion and the skin around it. Mycetoma eventually invades the subcutaneous tissue, fat, muscles and bone. This is usually gradual and delayed in eumycetoma while in actinomycetoma, it is earlier and extensive especially in infections induced by A. pelletierii (3). For unknown reasons, the tendons and the nerves are curiously spared until very late in the disease process, this may explain the rarity of neurological and trophic changes even in patients with long standing mycetoma. The absence of trophic changes may also be explained by the adequate blood supply in the mycetoma area.

In the majority of patients the regional lymph nodes are small and shotty. An enlarged regional lymph node is not uncommon and this may be due to secondary bacterial infection, genuine lymphatic spread of mycetoma or it may be due to immune complex deposition as part of a local immune response to mycetoma infection (7)(Fig3).

The infection remains localised and the constitutional disturbances are rare but when they do occur they are generally due to secondary bacterial infection of the open sinus tracts, fistula formation in some patients or generalised immuno-suppression. Cachexia and anaemia may be seen in late mycetoma. This is often due to malnutrition, sepsis and mental depression. Mycetoma can produce many disabilities, distortion and deformity. It can be fatal especially with cranial mycetoma (8,9,10,11).

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Site of Mycetoma:

The commonest site for mycetoma is the foot (79.2%), most of the lesions are seen on the dorsal aspect of the forefoot and for unexplainable reasons the left foot is affected more. The hand ranks as the second commonest site (6.6%), the right hand is more affected. This may imply a traumatic basis of the infection in this site. In endemic areas other parts of the body may be involved but less frequently and these include the knee, arm, leg, head and neck, thigh and the perineum. Rare sites such as the chest and abdominal walls, fascial bones, mandible, paranasal sinuses, eyelid, vulva, orbit, scrotum and surgical incisions may be affected (Fig 4).
 

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Differential Diagnosis:

The differential diagnosis of mycetoma includes many of the soft tissue tumours such as Kaposi's sarcoma, fibroma, malignant melanoma or fibrolipoma as well as thorn granuloma. The radiological features of advanced mycetoma may be comparable to osteogenic sarcoma and bone tuberculosis (1,3) Primary osseous mycetoma is to be differentiated from chronic osteomyelitis, osteoclastoma, bone cysts and from syphilitic osteitis.
 

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Diagnosis of Mycetoma:

Radiology:
 

A series of radiological changes are seen in mycetoma. This is due to the fact that all mycetoma agents are osteophilic and it may be due to the effect of the granuloma on both the affected bone and its blood supply. In the early stage, there is a soft tissue granuloma, which is shown as a dense shadow or as scattered multiple soft tissue shadows. Calcification and obliteration of the fascial planes may sometimes be seen As the disease progresses, the cortex may be compressed from outside by the granuloma leading to bone scalloping, this is followed by a variable amount of periosteal reaction. Periosteal new bone spicules are laid down at right angle to the cortex to create a sun-ray appearance and Codman triangle, an appearance that may be undistinguishable from that due to osteogenic sarcoma.  Late in the disease, there may be multiple punched out cavities through the normal density of the bone. These cavities are large in size, few in number with well-defined margins in eumycetoma. Whereas, the bone cavities in actinomycetoma are usually smaller in size, numerous and have no definite margins (1,3). The cavities are produced by the replacement of the osseous tissue by the grains. Their size is due to the size of the grains of the causative organism (Fig 5). The cavities are usually filled with solid masses of grains and fibrous tissue, which provides bone support. This may explain the rarity of pathological fractures in mycetoma.  The bony changes in the skull are unique: they are purely sclerotic with dense bone formation and loss of trabeculation.

Osteoporosis at and distal to the affected part is well observed in mycetoma and this may be due to disuse atrophy or due to the compression of the bone and its blood supply by the mycetoma granuloma. Chemotherapy causes radiological improvement consisting of remoulding, absorption of the sclerotic bone and reappearance of the normal trabecular pattern (1,3).

Ultrasonic imaging of mycetoma:

The mycetoma grains, its capsule and the accompanying inflammatory granuloma have characteristic ultrasonic appearances. Ultrasound imaging can differentiate between eumycetoma and actinomycetoma and between mycetoma and other non-mycetoma lesions. In eumycetoma lesions, the grains produce numerous sharp bright hyperreflective echoes, which are consistent with the black grains. The grain cement substance is most probably the origin of these sharp echoes. Also there are multiple thick walled cavities with absent acoustic enhancement. In actinomycetoma lesion the findings are similar but the grains are less distinct. This may due to their smaller size and consistency, individual embedding of the grains or the absence of the cement substances in few of them (Fig 6).

The ultrasonic diagnosis of mycetoma is more precise and accurate in lesions with no sinuses. The size and extent of the lesion can be accurately determined ultrasonically and this is useful in planning surgical incisions and procedures  (13).

Fine needle Aspiration Cytology of Mycetoma:

Mycetoma can be accurately diagnosed by Fine Needle Aspiration (FNA) cytology. Mycetoma lesion has a distinct appearance in a cytology smear characterised by the presence of polymorphous inflammatory cells consisting of an admixture of neutrophils, lymphocytes, plasma cells, histiocytes, macrophages and foreign body giant cells and grains. In sections, the grain is closely surrounded by and occasionally infiltrated by neutrophils causing its fragmentation. Outside the neutrophil zone, monocytic cells and giant cells are seen. This is surrounded by granulation tissue rich in fibroblasts and blood vessels. FNA allows morphological identification of mycetoma and its classification into eumycetoma and actinomycetoma, this is important as the treatment depends mainly on the aetiological agents.

The technique is simple, cheap, rapid, sensitive and can be tolerated by patients. It can be used not only in routine diagnosis but can be used as an effective mean in collection of material for culture and immunological studies. Due to the simplicity of the technique it can be used in epidemiological survey of mycetoma and for detection of early cases in which the radiological and serological techniques may not be helpful (14).

Culture:

A large variety of microorganisms are capable of producing mycetoma. They can be identified by their textural description, morphological and biological activities in pure culture. The biological activity may include, acid fastness, optimal temperature, proteolytic activity, utilization of sugars and nitrogenous compounds (15). The grains are the source of the culture and they should be alive and free of contaminants. Many culture media are in use e.g. Sabouraud, blood agar and Malt extract agar.  The culture technique is cumbersome, time consuming and chance contamination may give a false positive result. It also requires experience to identify the causative organisms.

The histological technique:

Stained sections usually show the grain morphology and the tissue reaction to the organisms (16). The technique is attractive in that it requires neither aseptic procedure nor the rigid time schedule required for culture, however it lacks the precision of culture.

Serodiagnosis in mycetoma:

In the absence of the classical triad of mycetoma, the demonstration of significant antibodies titers against the causative organism may be of diagnostic value. Serodiagnosis is of a great help in identification and classification of the various organisms, which is an essential prerequisite for medical treatment, and is mandatory for the follow-up of these patients. It has many advantages over the culture and histopathological techniques, as both require surgical biopsy, which may enhance the spread of the organism. The common serodiagnostic tests for mycetoma are the immunodiffusion (ID) and counter-immuno-electrophoresis (CIE) (17,18). The (ID) test is not sensitive enough and unless antigens are quite pure, it can be negative in early cases. (CIE) test remains reliable, simple, economical, rapid and a sensitive test. It is useful for routine diagnosis of early cases of mycetoma and for checking the sera that are weakly positive by (ID) test. It distinguishes between eumycetoma and actinomycetoma and between Actinomycetes themselves, but cross reactivity between A. madurae and A. pelletierii is quite common. However it is time consuming and the preparation of the antigens take a considerable time. Recently the indirect fluorescent antibody test was used in diagnosing mycetoma and was found to be specific and sensitive (19).

Enzyme linked immunosorbent assay (ELISA) was used in the diagnosis of mycetoma (20). It appeared to be a sensitive test for the detection of antibodies, however the high sensitivity of the test makes the cross reactivity unavoidable. ELISA may be a useful tool in community studies as sero-epidemiological survey could give valuable information on the distribution and prevalence of exposure to mycetoma (20).

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Management:

The treatment of mycetoma depends mainly on its aetiological agent and the extent of the disease. Until recently the only available treatment for mycetoma was amputation or mutilating surgical excision of the affected part. Local excision for localised lesion is not commonly performed as most of the patients present late with advanced disease. No case of self-cure has ever been reported in the medical literature.

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Eumycetoma Medical Treatment:

In many centres, surgery is the most acceptable line of treatment for eumycetoma cases. Usually it is in the form of aggressive surgical excision, debulking surgery or amputation in advanced disease  (25).

Reports of medical treatment in eumycetoma are few. A number of studies showed that ketoconazole could cure eumycetoma patients.  The dose is 300-400 mg daily.  The cure rate seemed to be dose dependent. Treatment of these patients may continue for periods ranging from few to many years (26).        

Recently Itraconazole was tried in the treatment of patients with eumycetoma, it had a high success and low recurrence rate. Patients showed good clinical response to 400 mg itraconazole daily. Surgical exploration revealed that, in all patients the lesions became well localized, encapsulated with thick capsule and were then easily removed surgically. There seems, no longer any justification for mutilating surgery or amputation prior to giving medical treatment. One disadvantage of these drugs is however, their current high cost, which may limit their availability to patients in poor countries.

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Treatment of Actinomycetoma:

Actinomycetoma is amenable to medical treatment with antibiotics and other chemotherapeutic agents. Combined drug therapy is always preferred to a single drug to avoid drug resistance and to eradicate residual infection. The common drugs in use include combination of streptomycin sulphate (14 mg/kg daily), diaminodiphenyl sulphone (dapsone) (1.5 mg/kg twice daily). If there is no response for few months or if there is persistent side effect then dapsone is replaced by Co-trimoxazole (14 mg/kg twice daily). An excellent therapeutic response to amikacin sulphate alone or in combination with Co-trimoxazole has been reported in the treatment of actinomycetoma (21,22,23,24).

In resistant cases other drugs such as rifampicin, sulfadoxine-pyrimethamine (fansidar) and sulphonamides had been tried, these proved to be effective in some cases and they remain a good second line therapy. Treatment must be continued until the patient is cured.

Many authors advocate giving mycetoma patients treatment for long periods and in higher doses as the microorganisms are locked in fibrous tissue with poor vasculature (21). The mean duration of treatment is usually more than one year. Medical treatment should be given pre and post operatively as it facilitates surgery, accelerates healing and reduces the chance of relapse. Medical treatment is useful in all stages of actinomycetoma even in large lesions with lymphatic spread, as well as in cases with a great deal of bone damage.  The cure rate varies between 60% and 90%. Recurrence is more common after an incomplete course of medical treatment and there is a good chance for the organism to develop drug resistance. Local administration of mycetoma chemotherapeutic agents was used but the results were not impressive.

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Surgery for Mycetoma:

Surgery in mycetoma is indicated when the disease process is limited and localised and for cases resistant to medical treatment or patients with bony involvement not responding to repeated long term conservative therapy.

The goal of surgery is the complete removal of the lesion or the reduction of size followed by medical treatment. Eumycetoma is well encapsulated and great care must be exercised not to rupture the capsule, which may lead to recurrence by transferring the fungal element into other parts of the operative field. Actinomycetoma has an ill-defined border; therefore a margin of healthy tissue should always be excised with the lesion. Simple bone curettage and soft tissue excision is recommended for localised bony lesions. A bloodless operative field using a tourniquet is mandatory to identify margins of the lesion. It is advisable to flood the wound at the end of surgery with tincture of iodine especially if there is doubt about the completeness of the excision or contamination of the surgical field (22). The wound can be closed primarily or by delayed primary sutures and in many cases skin grafts may be required. The open postoperative wounds are usually dressed with 2% iodine in glycerin. Glycerin is commonly used as it facilities the diffusion of the iodine into the tissue. Many dressing solutions are in use such as normal saline, Eusol solution but no one has advantage over the others.

 In advanced cases of mycetoma not responding to medical treatment for a prolonged period nothing short of amputation is likely to succeed. The amputation rate ranges from 25% to 50%. Extensive repeated excisions of the diseased tissue, including bone may be carried out several times to avoid the social consequences of amputation, This debulking procedure must be coupled with chemotherapy. In less advanced cases less mutilating surgery is advised for example, toe, mid tarsal or Syme's amputation. However, in many cases of inadequate surgery recurrence is inevitable.

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References:

1-Fahal AH, Hassan MA, Mycetoma. British Journal of Surgery.
1992; 79: 1138-1141

2-Abbott PH, Mycetoma in the Sudan. Transactions of the Royal Society of  Tropical Medicine and Hygiene. 1956; 50: 11-24.    

3-Mahgoub ES, Murray IG, Mycetoma. London, William Heinemann, Medical Books Ltd.  1973,  pp. 1-50.

4-Gonzalez-Ochoa A. Mycetoma in: Clinical Tropical Dermatology. Edited by Canizares O. Oxford, Blackwell Scientific. 1975; pp 24-29.

5-Magana M. Mycetoma. International Journal of Dermatology.
1984; 23(4): 221-236.

6-Gumaa SA. Mycetoma. Post-Graduate Doctor. 1983; 6: 15-20.

7-Fahal AH, Suliman SH. The clinical presentation of mycetoma.  Sudan Medical Journal.  1994; 32: 46-65.

8-Fahal AH, EL Sheik H, EL Hassan AM.      Pathological  fracture in mycetoma.   Transactions of Tropical Medicine and Hygiene - 1996; 90:  675-676.

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14-EL Hag IA, Fahal AH, Khalil EAG, Fine needle aspiration cytology of mycetoma. Acta Cytologica.  1996; 40(3):461-464.

15-Mahgoub ES. Mycetoma. Seminars of Dermatology. 1985; 4: 230-239.

16-EL Hassan AM, Fahal AH, EL Hag IA, Khalil EAG.          The pathology of mycetoma: Light microscopic and ultrastructural features. Sudan Medial Journal.  1994; 32: 23-54.

17-Gumaa SA, Mahgoub ES. Evaluation of the complement fixation test in the diagnosis of Actinomycetoma. Journal of Tropical Medicine and Hygiene. 1973; 76: 140-142.

18-     Gumaa SA, Mahgoub ES. Counter-immuno-electrophoresis in the diagnosis of mycetoma and its sensitivity as compared to immuno-diffusion. Sabouraudia. 1975; 13: 309-315.

19-Joshi KR, Singhvi S. Serodiagnosis of mycetoma.Transaction of the Royal Society of Tropical Medicine  and Hygiene.   1988; 82: 334.

20-Taha A.  A serological survey of antibodies to Streptomyces somaliensis and  Actinomadura madurae in the Sudan using enzyme linked immunosorbent (ELISA). Transaction of the Royal Society of Tropical Medicine  and Hygiene.. 1983; 77(1): 49-50.

21-Mahgoub ES.       Medical management of mycetoma. Bulletin of World Health Organization. 1976; 54: 303-310.   

22-Mahgoub ES .Medical treatment of mycetoma in the Sudan. Sudan. Medical Journal. 1994;32 (supp): 88-97.  

23-Mahgoub ES Treatment of actinomycetoma with sulphamethoxazole plus trimethoprim. American Journal of Tropical Medicine and Hygiene. 1972; 21(3): 332-335.

24-Welsh O, Saucceda E, Gonzalez J, Ocampo J. Amikacin alone and in combination with trimethoprim and sulfamethoxazole in the treatment of actinomycotic mycetoma. Journal of American Academy of Dermatology 1987; 17(3): 444-448.   

25-Fahal AH, Hassan MA, Sanhouri M. Surgical treatment of mycetoma.  Sudan Medical Journal.   1994; 32: 98-104.  

26-Mahgoub, ES, Gumaa SA. ketoconazole in the treatment of eumycetoma due to Madurella mycetomi. Transaction of the Royal Society of Tropical Medicine and Hygiene.   1984; 78: 376-379