• Mycetoma Research Center

    The Mycetoma Research Centre (MRC), University of Khartoum

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  • MRC Staff

    The staff members are of medical, health and science backgrounds who are interested in all facets related to mycetoma.

    MRC Staff:

    The staff members are of medical, health and science backgrounds who are interested in all facets related to mycetoma. They have rich track records in patients’ management, teaching, research and community development. The centre staff has continually explored new patients’ management approaches through clinical and basic research.

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  • Mycetoma at the WHO

     

    Mycetoma had landed safely at the Neglected Tropical Diseases of the WHO, Geneva after a long and challenging journey.

    The journal was planned, orchestrated and executed by devoted great and giants figures from The Sudan, The Netherland, United Kingdom, Mexico and Switzerland as well as prestigious organisations to mention but a few WHO-Sudan,           DNDi, Erasmus Medical Centre, University of Newcastle, Monterrey University, Swiss Tropical and Public Health Institute, Swiss Embassy -Sudan and last and not least           The Mycetoma Research Centre, Khartoum and University of Khartoum.

     

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Mycetoma Management Guidelines (pdf)

Evidence Based Guidelines
for Mycetoma patients’ management

Professor A. H. Fahal, MBBS, FRCS, MD, MS
Professor of Surgery
Mycetoma Research Centre
University of Khartoum
E.mail:
 

Introduction

Mycetoma is a chronic granulomatous, progressive inflammatory disease that involves the subcutanous tissue after a traumatic inoculation of the causative organism. It may be caused by true fungi (eumycetes) or by higher bacteria (actinomycetes) and therefore it is classified into eumycetoma and actinomycetoma respectively. The characteristic triad of a painless subcutaneous mass, sinuses and the discharge of grains is pathognomic of mycetoma. The lesion usually presents as a slowly progressive painless swelling at the site of previous trauma and gradually increases in size. It may spread to involve the skin and deep structures resulting in destruction of bone, deformity and loss of function with serious social and economic implications.  As mycetoma has a progressive course, it needs a long time to be cured, with a high recurrence rate, mycetoma patients preferably should be treated in a specialized clinic, the mycetoma clinic.

The mission of the Mycetoma Clinic

•      Maintenance of the highest standards of patient management.

•      Standardization of the diagnostic tools.

•      Standardization of the treatment of patients.

•      Maintenance of patients follow-up.

•      Establishment of the teamwork approach for the management   of

        patients.

The clinic members:

The members of the clinic include, general and orthopedics surgeons, pathologist, radiologist, mycologist, psychiatrist, pharmacist, physiotherapist, counseling nurse, secretary, social worker and paramedical staff.  The clinic team usually hold weekly meeting for fast and reliable means of communication and information exchange about the individual patients and to plan management.

The following are recommended diagnostic investigations for mycetoma

Radiology:

Many radiological changes are seen in mycetoma. These include:

1- Soft tissue granuloma, which appears as a dense shadow or as scattered multiple soft tissue shadows with calcification and obliteration of the fascial planes. The cortex may be compressed from outside by the granuloma leading to bone scalloping.

2- When the bone is involved there may be a periosteal reaction. This will lead to the formation of sun-ray appearance and Codman triangle, an appearance that may be indistinguishable from that of osteogenic sarcoma.

3- Formation of cavities that may be multiple punched out through out an otherwise bone of normal density. These cavities are large in size, few in number with well-defined margins in eumycetoma. The cavities in actinomycetoma are usually smaller in size, numerous and have no definite margins.

In the skull, the bone changes are purely sclerotic with dense bone formation and loss of trabeculation. Osteoporosis at and distal to the affected part is sometime observed in mycetoma and this may be due to disuse atrophy or to  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.

Ultrasonic imaging of mycetoma:

Mycetoma has a characteristic ultrasonic appearance. Ultrasound imaging can differentiate between eumycetoma and actinomycetoma and between mycetoma and other non-mycetoma lesions. In eumycetoma lesions, usually there are numerous, isolated sharp bright hypereflective echoes corresponding to the grains in the lesion. Single or multiple thick walled cavities with no acoustic enhancement are commonly identified and the cavities may contain debris and filaments.

In actinomycetoma lesions the findings are similar but the grains are less distinct. This may be due to their smaller size and consistency, individual embedding of the grains or the absence of the cement substances in some species. The echoes are commonly settled at the bottom of the cavities.

The technique is safe, simple, accurate and useful in planning surgical treatment.  

Fine needle Aspiration Cytology of Mycetoma:

Mycetoma can be accurately diagnosed by Fine Needle Aspiration cytology (FNA). 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, and sensitive and can be tolerated by patients. It can be used for diagnosis, collection of material for culture and immunological studies and for mycetoma epidemiological surveys.

Culture:

The mycetoma causative organisms 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. The grains are the source of the culture and they should be alive and free of contaminants and they are usually obtained by deep surgical biopsy. Grains should be sent immediately in sterile containers to the laboratory for culture. Many culture media are in use; they include Sabouraud, blood agar and Malt extract agar.  Although culture is a the gold standard in the diagnosis of mycetoma, the  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 diagnosis:

Stained sections usually show the grain morphology and the tissue reaction to the organisms. There are three types of tissue reactions:

Type I:  The grain is surrounded and sometime invaded by an intense neutrophil polymorphonuclear leucocyte infiltrate.

Type II:  There is a vascular layer containing macrophages, lymphocytes, plasma cells and giant cells. The giant cells usually contain fragments of the grain. Some macrophages may have a foamy cytoplasm.

Type III: Formation of pure epithelioid granuloma.

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 and it needs deep surgical biopsy which may enhance the spread of the organism. Biopsies are usually fixed in 10% formal-saline.

Serodiagnosis in mycetoma:

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. The common serodiagnostic tests for mycetoma are:

1-     Counter-immuno-electrophoresis (CIE)

2-     Enzyme linked immunosorbent assay (ELISA)

These tests are not sensitive enough and unless antigens are quite pure, it can be negative in early cases. They are simple, economical but are time consuming and there is cross-reactivity between the individual organisms. (ELISA) appears 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 sero-epidemiological surveys.

The treatment of mycetoma

The treatment of mycetoma depends mainly on its aetiological agent and the extent of the disease. Until recently, in many centres, the only available treatment for mycetoma was amputation or mutilating surgical excision of the affected part.

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 regimes are:

1- Amikacin sulphate (15 mg/kg) in combination with Co-trimoxazole

(14 mg/kg twice daily) is the first line for actinomycetoma treatment.

In resistant cases other drugs can be used and this includes:

2- Streptomycin sulphate (14 mg/kg daily) combined with Co-trimoxazole (14 mg/kg twice daily)

 3- Streptomycin sulphate (14 mg/kg daily) combined with Rifampicin (15-20 mg/kg daily).

Treatment must be continued until the patient is cured. 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 with advanced disease.  The cure rate varies between 60% and 90%. Drug resistance and recurrence are commonly seen with incomplete and interrupted treatment.

Treatment of Eumycetoma :
The common drugs regimes are:

 1- Ketoconazole: the dose is 400-800 mg daily.  The cure rate seemed to be dose dependent.

2- Itraconazole, has a good success and low recurrence rate. Patients showed good clinical response to 400 mg itraconazole daily.

Treatment of these patients may continue for periods ranging from few to many years. The liver function of the patients should be checked before and during treatment as these drugs may affect the liver.

The treatment is usually stopped with clinical, serological, radiological and ultrasonic cure.  The criteria for cure are:

1: Disappearance of the subcutaneous mass, healing of the sinuses and the skin return to normal.

2: Three consecutive negative CIE test one month apart.

3: The bone regains its normal radiological appearance with remodeling.

4: The absence of hyperreflective echoes and cavities on ultrasonic examination.

5: No grains are seen in FNA.

Surgery for mycetoma:

The goal of surgery in mycetoma is complete removal of the lesion or the reduction of size followed by medical treatment. Local anaesthesia is contra-indicated as the extent of the disease is always difficult to ascertain preoperative. 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 to destroy any missed grains. The wound can be closed primarily and in many cases, skin grafts may be required. The open postoperative wounds are usually dressed with 2% iodine in glycerin to destroy any fungal elements. In post-operative dressing normal saline and Eusol solution can be used but they have no 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. 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.

Evidence based recommendations for the work up for patients with mycetoma:

 Diagnosis can be established by the following:

·         Good clinical interview

·         Through loco-regional and general clinical examination

·         X-Ray of the affected part in anterio-posterial and lateral views

·         Ultrasonic examination of the affected part

·         FNA from the lesion

·         Surgical biopsy is done under General or spinal anaesthesia with a tourniquet. Surgical biopsy is divided in to two parts, one part is sent in sterile container for culture and one fixed in 10% formal saline for histopathological examination.

Medical treatment

For actinomycetoma it is recommended to star with the following regime:

Streptomycin sulphate (14 mg/kg daily) intramuscular daily for four weeks then it is given on alterative days and Diaminodiphenyl sulphone (dapsone) (1.5 mg/kg twice daily).

If there is no response for few months or if there is persistent side effects then dapsone is replaced by Co-trimoxazole (14 mg/kg twice daily) or Rifampicin (15-20 mg/kg daily). For massive lesions Co-trimoxazole, rifampicin and Streptomycin sulphate can be combined together.

 For eumycetoma the following is recommended:

1- Ketoconazole: the dose is 400-800 mg daily.

2- Itraconazole: the dose is 400 mg daily.

Treatment of mycetoma patients may continue for periods ranging from few to many years. The liver function of the patients should be checked before and during treatment as some of these drugs are hepato-toxic.  The treatment is usually stopped with clinical, serological, radiological and ultrasonic cure.   

In all patients the medical is stated before surgery and continued postoperatively to avoid recurrence.

Surgical treatment:

Surgical excision is recommended for small localized lesions, debulking of massive lesions; for better response to medical treatment and for lesions became well encapsulated by medical treatment.

Amputation rarely done nowadays. It is done for very advanced lesions with bad general condition and as a life saving procedure.

Follow up

Every eight week if possible for assessment of treatment and cure and for early detection of recurrence. Frequent check x-ray, full blood count and liver functions are recommended for patients on medical treatment.