Mycetoma is a chronic subcutaneous infection characterized by localized swelling and draining sinuses that expel grains. It is caused by fungi or bacteria trapped in the skin after trauma. Diagnosis involves examining grains for morphology and staining characteristics to identify the causative agent. Definitive diagnosis requires demonstrating grains microscopically, visualizing medlar bodies, or isolating the organism in culture. Differential diagnosis includes other granulomatous or neoplastic conditions. Management involves long-term antibiotic or antifungal therapy depending on whether an actinomycete or fungus is identified as the cause.

1. DEPARTMENT OF DEMATOLOGY ,VENEREOLOGY AND
LEPROLOGY
J.J.M MEDICAL COLLEGE ,DAVANGERE-577004
SEMINAR ON
MYCETOMA
CHAIRPERSON: PRESENTED BY:
DR.B. K. VISHWANATH DR. RAVINDER YADAV
PROFESSOR 18.12.2018

3. CONTENTS
• INTRODUCTION
• HISTORY
• EPIDEMIOLOGY
• ETIOLOGY
• PATHOLOGY AND PATHOGENESIS
• CAUSATIVE AGENTS
• RISK FACTORS
• CLINICAL FEATURES
• DIAGNOSIS
• DIFFERENTIAL DIAGNOSIS
• LABORATORY DIAGNOSIS
• TREATMENT
• CONCLUSION
• REFERENCES

4. INTRODUCTION
• SYNONYMS: Madura foot, Maduromycosis and
Podal koma
• DEFINATION:
Mycetoma is a chronic , suppurative, granulomatous
non contagious disease of subcutaneous tissue and
bones, characterized by localized swellings with
multiple sinuses discharging granules that are micro
colonies of causative agent.

5. MADURA FOOT

7. HISTORY
• The oldest known case of mycetoma may date as far
back as the byzantine period (300-600 AD) with
possible evidence from an adult skeleton suggesting
mycetoma based on morphological changes in bone.
• Oldest description of the disease found in ancient
indian sanskit text’ Athrava Veda` in which refence is
made to `Pada Valmikam` meaning `Anthill foot`.

8. • First described by John
gill in 1842 with the
term ‘Madura foot’,it
was first noticed in
district of Madura,
India.
• In 1860, carter
introduce the term
mycetoma to all tumors
produced by
fungi,(fungal tumor)

9. Piroy: introduced the term

10. EPIDEMIOLOGY:
.Mycetoma is more common in individuals who
have more frequent and direct contact with the
field environment, such as farmers, herdsmen,
and other field laborers.
• Adult males most commonly affected
• Maximal incidence seen in 21-40 years age
group
• Male:Female ratio of 3:1 to 5:1.

11. • Micro-organisms are saprophytic in nature (soil and
plants) and derive nutrition from decomposed organic
matter.
• Some species have worldwide distribution while some
are limited to certain regions.
• Ecological environment determines presence and
prevalence of different agents.
• Common in tropical and subtropical areas sp. among
agricultural workers.
• Endemic in India and various countries like sudan,
somalia, yemen, mexico, venezuela and argentina.

13. • In India actinomycotic mycetoma is more
common, while in north part of India
eumycetoma is common.
• Actinomycetoma is more prevalent in drier
areas, whereas eumycetoma is more common
in sites with more rainfall.
• In India, Nocardia species and Madurella
grisea are the most common causes of
mycetoma.

14. ETIOLOGY
Caused by saprophytic fungi and bacteria from soil or
plants,which penetrates skin and subcutaneous tissue by
traumatic implantation.
Mycetoma caused by –
• Fungus(Eumycetoma)
• Aerobic actinomycetes(Actinomycetoma)

15. Eumycoticmycetoma agents
Most frequently isolated are:
• Madurella mycetomatis and
• Madurella grisea.

16. Less frequently –
• Pseudalleschemia boydii.
• Species of Acremonium.
• Exophiala jeansilmei.
• Leptosphaeria senegalensis.

17. COMMON CAUSAL AGENTS OF ACTINOMYCOTIC MYCETOMA AND GRAIN
CHARACTERISTICS
Agent
GRAINS
Color
Approximate
diameter
(mm)
Histology (H&E stain)
M. mycetomatis Black-
to-brown
1.0 Large, dark brown, lobulated
Compact type : With even distribution of
brownish cement intersected by a
network of hyphae
Vesicular type : With peripheral
localization of brown cement around
hyaline hyphae and chalamydospores,
brown pigment particles in hyphal cells.
M. grisea Black-
to-brown
1.0 Small, oval or lobed; hallow center with
loose hyaline hyphae, dark colored
periphery with a network of hyphae and
chlamydospores embedded in brown
cement; brown granules of intracellular
pigment absent.
L. senegalis Black 1.0 Small, irregular, tubular or hollow;
central core of hyaline hyphae,
periphery dense with black hyphae and
large vesicular cells imbedded in black
cement.

18. P. romeroi Black 1.0 Small, tubular, central network
of hyphae with a thick band "of
chlamydospores in the
periphery, dark swollen cells in
the outer edge surrounded by an
eosinophilic zone.
P.
jeanselmei
Brown-to-
back
1.0 Small, vermiform crescent
crescent shaped; hollow center;
hyphae and chlamydospores;
brown cement absent
P. boydii White-, to-
pale yellow
1.0 Large, round or lobulated; broad
septate hyaline hyphae with
numerous swollen hyphal cells
(>20µm)
Acremoniu
m spp.
White-
to-
yellow
or black
1.0 Small; irregular; hyaline
hyphae with numerous
swollen cells (<12µm)
surrounded by an eosinophilic
zone.

19. Actinomycoticmycetoma agents
• Species of Nocardia esp. N. brasiliensis .
• Actinomadura madurae
• Streptomyces somaliensis and
• Actinomadura pelletiera

20. • Infections evolve slowly by contiguity.
• Can invade deeper structures like fascia, muscles,
tendons, bones and adjacent organs.
• Nutritional factors and repeated trauma contribute to
development of mycetoma.

21. COMMON CAUSAL AGENTS OF ACTINOMYCOTIC MYCETOMA AND
GRAIN CHARACTERISTICS
Agent
Grains
Color
Approximate
diameter
(mm)
Histology (H&E stain)
N.asteroides White 0.5
Small, round, oval or vermiform;
homogeneous loose clumps of
filaments, partially stained by
hematoxylin
N.brasiliensis White 0.2 Same as above
N.otitidiscaviarum
(caviae)
White 0.5 Same as above
A.madurae White 2.0
Large, round or lobulated; center
eosinophilic, amorphous; dense
basophilic mantle peripherally
A.pelletieri Red or pink 1.0
Small, round or irregular with
denticulate edge; homogeneous
matrix staining deeply with
hematoxylin; no clubs
S.somaliensis
White-
to-yellow
1.0
Variable size; round or oval with
smooth borders; center amorphous
lightly stained; no clubs

22. PATHOLOGY AND PATHOGENESIS
• Entry of organisms via thorn pricks, wood splinters or pre-
existing abrasions or trauma.
• After inoculation, normally non-pathogenic organisms grow
and survive through production of grains/granules/sclerotia,
structures composed of masses of mycelial fungi or bacterial
filaments and a matrix component.
• In Eumycetoma, hyphal elements have thickened cell-wall
towards periphery of the grains, conferring protection against
host immune system. The grains are seen histopathologically
within abscesses containing polymorphonuclear cells.

23. • Complement dependednt chemotaxis of PMN
leukocyes is induced by both fungal and
actinomycotic antigen in vitro. In diseased state,
failure of cells of innate immune system to engulf
and inactivate the causative organisms occurs.
• Abscesses containing grains are seen in association
with granulomatous inflammation and fibrosis.

24. • 3 types of immune responses observed in response to
grains of mycetoma.
Type I response: Neutrophils degranulate and adhere to
grain surface leading to gradual disintegration of grain.
Type II response: Characterized by disappearance of
neutrophils and presence of macrophages to clear grains
and neutrophilic debris.
Type III response: Formation of epithelial granuloma.
• These host responses do not control infection but
accounts for partial spontaneous healing seen in
mycetoma.

25. ADDITIONAL POINTS:
• It is not clear whether person developing mycetoma have predisposing
immune deficits. Disease doesn't appear to be more common in immune-
compromised host.
• Establishment of mycetoma in animal model is accomplished only in
athymic, nude (CMI deficient) mice, suggesting an important role of CMI
system. Greater prevalence of disease in men is not completely explained
by increased exposure to soil and plant material.
• Progesterone (in vitro) inhibits growth of M.mycetomatis, P.romeroi and
N.brasiliensis. In study of N.brasiliensis, estradiol limited disease produced
in animals.
• If immune dysfunctions play any role in influencing development of
mycetoma in an individual, it is likely a minor deficit in CMI.

26. RISK FACTORS
• Poor hygiene
• Walking barefoot
• Necrotic injured tissue
• Decreased nutrition
• Decrease use of
protective
clothing,chiefly shoes in
warmer and poor
endemic regions.
• Diabetes mellitus

28. CLINICAL FEATURES
• Incubation period - weeks and months.
• Common sites- foot and lower leg (70%), hands
(15%), followed by upper extremities and other
areas of the body exposed to trauma.
• First a single, small, painless subcutaneous nodule
which later increase in size, become fixed to
underlying tissues and ultimately develop sinus
tract beneath the lesions discharging serosanginous
or seropurulent discharge.

29. Note:
Progression to draining sinus tracts take weeks,
months and even years, occurring more rapidly in
actinomycetoma.
• Overlying skin is smooth and shiny, commonly
fixed to underlying tissue.
• Skin may be hypo- or hyper-pigmented with
signs of both healed and active sinuses
displaying a cycle of spontaneous healing of all
sinuses tracts and simultaneous spread of
infection to new areas.

30. • Swelling is often firm and non-tender and
overlying skin is not erythematous.
• Extension to underlying bones and joints give rise
to periositis, osteomyelitis and arthritis.
• In advanced cases, destruction of bone within an
infected area may be almost complete, resulting in
gross deformity.
• The condition becomes very painful with
involvement of bones or with secondary bacterial
infections.
• Degree and extent of bone involvement vary with
species of infecting agent.

33. SITES OF MYCETOMA
Occurrence Site
Common Feet (~70-80%)
Hands (~12%)
Legs
Highly endemic regions
Arm
Head/neck
Thighs
Perineum
Rare
Chest
Abdominal wall
Facial bones
Mandible
Paranasal sinuses
Eyelid
Vulva

34. • In Eumycotic mycetoma ,lesions are usually single or
multiple , punched out lytic area with well defined
walls and little sign of bone reaction .
• In actinomycotic mycetoma, lesions are
inflammatory and suppurative , both osteolytic and
osteosclerotic changes present as same time.
• Destruction of ligaments and articular surface results
in ankylosis of joints, bone destruction and limb
deformities.
• Hematogenous spread to regional lymph nodes has
been reported in Nocardia and streptpomyces where
encapsulation is rare.

35. COMPLICATIONS
• Secondary bacterial infections
• Local abscess formation
• Cellulitis
• Bacterial and tubercular osteomyelitis
• Rarely septic death may occur.
• Lymphodema
• Anaemia,depression,toxicity due to prolonged
medications.

36. PATIENT EVALUATION AND DIAGNOSIS
When mycetoma is suspected, one should
investigate the following:
1.History of trauma.
2.Presence of increased volume of affected area,
formation of nodules, abscess, fistulae and
drainage of grains.
3.Color and size of grains and their microscopic
characterstics (in 10% KOH fresh mount)to
classify agents as either fungus or filamentous
bacteria .

37. 4. Histopathology of lesion
5.Culture for isolation and identification of agent.
6. Imaging study to evaluate degree of extension
of lesion with X-ray and CT SCAN and MRI
studies for bone lesions and alteration in soft
tissues.
7. Clinical diagnosis of mycetoma can made by
the classic triad of painless soft tissue swelling,
draining sinus tracts and extrusions of grains.

38. Classical triad
 Localized swelling
 Underlying sinus tract
 Production of grains within a sinus tract

39. 8.Clinical suspicionis are confirmed by:
 Demonstration of grains in pus or
 Visuallization of Medlor bodies(globular
colonies of infecting organism).
 Isolation of oragnism on culture.

40. CLINICAL DIFFRENTIAL DIAGNOSIS
1) Botryomycosis and actinomycosis .
2) Cutaneous tuberculosis and bacterial osteomyelitis.
3) Neoplasm like SCC,kaposi’s sarcoma,syphilis, yaws,
leprosy, tuberculosis, cutaneous leishmaniasis, and
mycoses may mimic mycetoma.
4) Very early lesions may be mistaken for fibroma, lipoma,
sebaceous cyst, dermoid cyst, foreign body granuloma
and chronic abscess.

41. LABORATORY DIAGNOSIS
• Collection of sample
• Direct examination of grains.
• Serological tests.
• Histopathology.
• Culture.
• Imaging studies.

42. Collection of samples:
 Pus or exudates discharging or obtained by aspiration
of biopsied tissue ideally from the edges and centre
of lesion are required for satisfactory diagnosis.
 Delay in processing will increase the likehood of
bacterial or saprophytic fungi contaminating
samples.
 Biopsy specimens intended for culture must be
placed in sterile saline or wrapped in moistened
sterile gauze.

43. DIRECT EXAMINATION-
• The grains can be collected by saline dressings
applied over the swelling for 24 hours.
• Grains are usually 0.2 to 5 mm in diameter,
and thus may be observed grossly without
magnification.
• The color of the grain should be noted.
• Black grains are almost always Eumycotic,
• Red grains are due to Actinomadura
pelletierii.

44. • White or pale grains may be either eumycotic
or actinomycotic.
• A KOH mount and gram stain should be
performed on grains. It is useful to
differentiate between fungal and bacterial
etiology.

46. Nocardia Madurella.M

47. Serological tests:
ELISA- for detection of antibodies in
mycetoma infections.
PCR- identifies Species based on amplification
of a region of ribosomal gene complex.
Counter immunoelectrophoresis – M/C used.
Immunodiagnosis using stains for
neutrophils(CD15), macrophages (CD68) and
lymphocytes (CD3).

48. Histopathology-
• Histological sections of the biopsy materials are
examined for the presence of characteristic
granules within the abcess cavity.
• H&E stain- Splendore Hoeppli phenomena (
grains are surrounded by an eosinophilic
material), accumulation of PMNs producing
microabscess, chronic inflammatory infiltrates
and granulation tissue containing epitheloid and
giant cells.
• Grains are found at the centre of the
inflammatory response or in the pus discharged
from the sinuses.

49. Splendore Hoeppli phenomenon

51. • Note:
In Eumycotic mycetoma grains are first identified
in H& E stain and the fungal elements are
identified using PAS and Grocott staining for
hyphae.

52. Culture-
• Deep biopsy used for culture.
• Cultured on mycologic and mycobacterial
media and held for 4 weeks.
• Grains after washing in saline are inoculated
on Sabourauds’s dextrose agar, blood agar,
Malt extract agar and brain heart infusion
agar to isolated for fungi and bacteria, with or
without antibiotics and incubated at 26 degree
and 37 degree respectively.

53. M.MYCETOMATIS NOCARDIA

54. IMAGING STUDIES
• X-RAY: early feature:soft tissue granuloma
• Bone expension ,cortical scalloping,periosteal
reaction and punched out cavities appear.
• Eumycetoma:few cavities usually >1cm
• Actinomycotic: smaller cavities but more in
no.

55. normal mycetoma

56. USG: Successfully diffrentiate the mycetoma from
osteomyelitis or tumor
• EUMYCETOMA
Sharp hyperechoic foci
• Actinomycotic mycetoma
Fine hyperechoic foci

57. MRI - For accurate assessment of disease extent
DOT IN CIRCLE SIGN

58. PREVENTION
• No preventive vaccine is available against
mycetoma.
• Prevention is best accomplished by impacting
on the incidence of the traumatic inoculation
of causative agents. Wearing of shoe and
clothing to protect against splinters and thorn
pricks should be stressed.
• Complications can be prevented by early
identification and treatment of lesions usually
with minor surgery and chemotherapy.

59. TREATMENT
Points to remember:
• It is important to characterize etiologic agent to
determine nature of infections whether bacterial or
fungal and to evaluate extent of tissue invasion.
• Specific therapy depends upon the identification of
causative agents and determination of its drug
sensitivity.
• Therapy should be continued for several months after
clinical cure to prevent a relapse.

60.  Exploration and drainage of sinus tract, debridement of diseased
tissue and removal of bone cyst assist greatly in healing.
 Treatment of Eumycetoma is generally less successful than for
Actinomycetoma.
 Drugs of choice- Itraconazole, Ketoconazole and Amphotericin-
B.
 Dosage: In adult weighing upto 60kg.
 Itraconazole 200-300mg/day
 Ketoconazole 400mg/day
 Amphotericin B 50mg/kg body weight IV daily.
 Isolated cases of successful treatment with Voriconazole (200mg
PO bid for several months) and Posaconazole (400mg bid or 200mg
qid) have been reported.
 The duration of treatment depends on severity of disease and
patient’s response

61. • Therapy is suggested for one to two years for
complete eradication unless adverse effects
warrant cessation of medication.
• Surgical treatment in the form of amputation
remains a variable therapy for mycetoma
caused by fungi.

62. TREATMENT OPTION FOR EUMYCOTIC MYCETOMA

63. Actinomycetoma esp. caused by nocardia:
• Sulfamethoxazole 1200mg + trimethoprim
240mg bid
• Dapsone 100-300mg/day for 2-3 years.
• Oxytetracycline 1.5-2 g and Minocycline
200mg/day for 1-2 years is used to treat
N.brasiliensis, N.asteroides and A.madura and
A.pelletieri.
• Amoxycillin 500md and Clavulinic acid 125 mg
tid x 6 months: for N.brasiliensis

64. • Amikacin 15mg/kg/day IM bd or tid for 3
weeks used alone or in combination with
cotrimoxazole.
• Amikacin with sulfamethoxazole is the best
treatment for cases caused by N.brasiliensis
and A.madura unresponsive to conventional
treatment or those with potential
dissemination to underlying organs. Given in
cycles of 5 weeks.

65. • Sulfamethoxazole(80mg) +
trimethoprim(40mg)/kg/day x 5 weeks.
Creatinine clearance and audiometry done
periodically every cycle to detect aminoglycosides
side-effects.
• Corticosteroids with antifungals for a short period
improve inflammatory processes.
• Combination of surgery and drug therapy is the
best option.
Note:
Treatment failure in mycetoma is due to intense
fibrosis and low sensitivity to etiologic agents to the
current antifungals.

66. CONCLUSION
• Myecetoma is a rare form of infection caused
by saprophytic organisms commonly seen in
tropical and sub tropical regions.
• Initial lesions are usually asymptomatic and
definite diagnosis is difficult as it can resemble
other conditions.
• Thus early diagnosis is of utmost importance.

67. SUMMARY

69. REFERENCES
1. Dermatology in general medicine-Fitzpatick
2. Textbook of dermatology-Rooks
3. Textbook of dermatology-IADVL
4. Textbook of dermatology-Moshella
5. Handbook of dermatology and color atlas
6. Bolognia text book of dermatology.
7. Tropical dermatology-Stephen K.Tyring et al.
8. Vineet Relhan,khusboo Mahajan,pooja agarwal vijay kumar
Garg Mycetoma :An update ,IJD 2017,62(4):332-340