01Approach to the Critical Patient/attcp33

Immediate priorities

›Airway and systemic threats

›Secondary bacterial sepsis from mycetoma

›Fever with systemic signs and spreading cellulitis

›Hypotension SBP < 90 mmHg or MAP < 65 mmHg

›Tachycardia and altered mental status

›If septic shock present, broad-spectrum antibiotics within 1 hour

›Class I recommendation for sepsis bundle initiation

›Source control planning for infected mycetoma mass

›Limb-threatening complications

›Advanced bone destruction with structural failure

›Uncontrolled secondary infection with necrotizing features

›Impending or planned amputation

Monitoring and targets

›Monitoring priorities

›Vital signs trend for secondary infection

›Temperature normalization target

›Heart rate and blood pressure stability

›Wound and lesion status

›Sinus tract output volume and character

›Signs of local spread or satellite lesion formation

›Drug toxicity surveillance

›LFTs during itraconazole therapy every 1 to 3 months

›Renal function and audiometry during amikacin cycles

Consultation triggers

›Specialty referral indications

›Infectious disease

›Organism identification and antimicrobial guidance

02History/hx64

Presentation pattern

›Classical triad

›Painless or minimally tender subcutaneous mass

›Typical "woody" induration

›Slowly enlarging over months to years

›Sinus tract formation

›Multiple draining sinuses

›Sero-purulent or purulent discharge

›Characteristic grain discharge

›Black or dark grains suggest eumycetoma

›White, yellow, or red grains suggest actinomycetoma

›Timeline and progression

›Onset following minor skin trauma

›Thorn prick or splinter injury

›Contact with soil during outdoor work

›Incubation variability

›Ranges from 3 months to 50 years

›Initial nodule at inoculation site

›Functional impact trajectory

›Loss of joint range of motion

›Difficulty walking or working

Risk factors

›Demographic risk profile

›Sex predominance

›Male-to-female ratio approximately 2.5 to 3:1

›Male agricultural workers most affected

›Age at peak incidence

›15 to 45 years with peak at 20 to 30 years

03Physical Exam/exam47

Vitals and general

›Systemic stability assessment

›Temperature

›Fever indicates secondary bacterial infection

›Normal temperature typical in uncomplicated mycetoma

›Blood pressure

›Hypotension trigger for sepsis evaluation

›SBP < 90 mmHg or MAP < 65 mmHg as alarm thresholds

›Heart rate and respiratory rate

›Tachycardia with secondary infection

›General appearance for systemic illness

Lesion and skin examination

›Lesion characterization

›Firm woody induration on palpation

›Non-tender or minimally tender baseline

›Fluctuance suggesting secondary abscess

›Sinus tracts

›Number and distribution

›Active discharge character and grain presence

›Size and extent measurement

›Longest dimension in cm

›Satellite lesions

›Grain morphology

›Color, size, and consistency

›Black grains: eumycetoma (Madurella mycetomatis)

›White to yellow grains: actinomycetoma (Actinomadura madurae, Nocardia brasiliensis)

›Limb and joint assessment

›Range of motion

04Differential Diagnosis/ddx51

Early lesion mimics

›Non-infectious subcutaneous masses

›Foreign body granuloma

›History of penetrating injury

›No grain discharge

›Fibroma or fibrolipoma

›Non-inflammatory

›Soft or rubbery consistency

›Neurofibroma

›Neural tract association

›ICD-10 D36.10

›Kaposi sarcoma

›Violaceous plaques and nodules

›HIV association

›ICD-10 C46.0

›Infectious mimics in early stage

›Sporotrichosis

›Lymphocutaneous spread pattern

›Rose gardener or soil exposure

›ICD-10 B42.9

›Phaeohyphomycosis

›Dematiaceous fungi

›No grain production

›Botryomycosis

›Bacterial etiology (Staphylococcus, Pseudomonas)

›Grains present but bacterial in nature

Advanced disease mimics

›Malignant mimics

05Laboratory Tests/lt62

Grain and microbiological studies

›Grain examination

›Grain collection technique

›Express from sinus or fine needle aspiration

›Deep-seated grains preferred over extruded ones

›Less contamination and more viable organisms

›Direct microscopy

›Crush preparation under cover glass

›Fine filaments on Gram stain: actinomycetoma

›Broad septate hyphae on PAS stain: eumycetoma

›Calcofluor white stain

›Fluorescent detection of fungal hyphae

›Useful adjunct to PAS

›Ziehl-Neelsen stain

›Identifies Nocardia species

›Modified ZN stain preferred for Nocardia

›Culture

›Plate grains on appropriate media

›Incubate minimum 4 weeks

›Culture yield low, especially actinomycetoma approximately 27%

›Media selection

›Sabouraud dextrose agar for fungi

›Blood agar and selective media for actinomycetes

Histopathology and molecular studies

›Deep biopsy histopathology

›H&E stain

›Reliably distinguishes fungal from bacterial etiology

›Granulomatous reaction with grain identification

06Diagnostic Tests/dt68

Scoring Systems

›Mycetoma Activity and Severity Clinical Scale (MASS)

›Severity scale components

›Maximum score 24

›Assesses lesion size, bone involvement, sinus number, limb function

›Activity scale components

›Maximum score 10

›Assesses active discharge, grain production, new sinus formation

›Limitations

›Inter-rater reliability remains limited

›International Delphi consensus development 2025

›Not yet validated for treatment response prediction

›Clinical staging framework

›Stage by extent of tissue involvement

›Soft tissue only: early stage

›Bone involvement: advanced stage

›Joint or distant spread: very advanced

›Prognostic factors

›Small lesion size strongest positive predictor of cure (OR 10.09)

›Good follow-up second strongest predictor (OR 6.81)

›Prior surgical recurrence predicts amputation (OR 3.67)

MRI

›MRI indications for mycetoma

›Gold standard for lesion extent delineation

›Soft tissue boundaries and depth

›Bone marrow involvement

›Surgical planning prior to excision

›Pathognomonic sign

07Disposition/dispo35

Outpatient management

›Outpatient criteria

›Uncomplicated mycetoma without secondary infection

›Stable vital signs

›Oral medication tolerance

›Established diagnosis and treatment plan

›Organism type identified

›Treatment regimen selected

›Reliable follow-up possible

›Adherence assessment

›Access to monitoring labs

›Outpatient follow-up schedule

›Active treatment phase

›Every 4 to 6 weeks during initial treatment

›LFT monitoring for itraconazole monthly

›Radiological reassessment

›Clinical and imaging evaluation every 3 to 6 months

›Plain radiograph for bone involvement monitoring

Inpatient and surgical admission

›Admission indications

›Secondary bacterial sepsis

›Systemic infection with hemodynamic instability

›IV antibiotics required

›Surgical intervention

›Excision or debridement under general anesthesia

›Amputation for unresponsive advanced disease

›Initiation of parenteral amikacin cycles

›Monitoring for nephrotoxicity and ototoxicity

08Treatment/t80

Eumycetoma antifungal therapy

›First-line antifungal

›Itraconazole

›200 mg orally twice daily (400 mg per day total)

›Minimum 12 months duration pre-operatively

›Take with food for enhanced absorption (capsule formulation)

›Combine with surgical excision for optimal outcomes

›Monitoring requirements

›LFTs at baseline then every 1 to 3 months

›Drug interaction review (CYP3A4 inhibitor)

›QT prolongation risk with concomitant QT-prolonging drugs

›Emerging alternative antifungal

›Fosravuconazole

›200 mg orally once weekly

›No food requirement (advantage over itraconazole)

›Fewer drug interactions

›Phase 2 randomized trial shows comparable efficacy to itraconazole

›Practical advantage in resource-limited settings

›Refractory eumycetoma options

›Voriconazole

›Promise in refractory cases

›LFT and visual monitoring required

›Posaconazole

›Extended-release tablet 300 mg daily after loading

›Option when itraconazole fails or is not tolerated

›Agents without activity

›Amphotericin B: poor in vitro activity against Madurella

›Echinocandins: no activity against eumycetoma agents

›Terbinafine: limited efficacy

›Ketoconazole: restricted or withdrawn due to hepatic toxicity and adrenal suppression

Actinomycetoma antibacterial therapy

›First-line regimen

›Co-trimoxazole (TMP-SMX) with amikacin cycle protocol

›Co-trimoxazole 48 mg/kg/day orally in divided doses

›5-week cycle duration

›Amikacin 15 mg/kg/day IV divided every 12 hours

›Amikacin given during first 3 weeks of each cycle

›2-week amikacin-free interval for toxicity monitoring

›Up to 4 cycles total

›Cure rates up to 90% with this regimen

›Amikacin monitoring protocol

›Renal function

›Serum creatinine before each cycle

›Hold if rising creatinine trend

›Audiometry

›Baseline and during amikacin-free interval each cycle

›Discontinue if sensorineural hearing loss develops

›Refractory actinomycetoma

›Amikacin plus carbapenem

›Imipenem-cilastatin 500 mg IV every 6 hours or meropenem 1 g IV every 8 hours

›Check minimum inhibitory concentrations for resistant strains

›Rifampicin plus TMP-SMX

›Effective for Nocardia species

›Rifampicin 600 mg orally daily

›Co-amoxiclav (amoxicillin-clavulanate)

›When co-trimoxazole allergy present

›Generally not effective against Actinomadura madurae alone

›Acquired resistance risk with monotherapy

Surgical management

›Surgical indications and principles

›Eumycetoma surgical approach

›Excision after minimum 12 months of antifungal therapy

›Wide excision margins to reduce recurrence

›Mandatory post-operative antifungal continuation

›Surgery alone has up to 90% recurrence without antimicrobials

›Actinomycetoma surgical role

›Surgery rarely needed

›Reserved for debridement of necrotic tissue

›Drainage of loculated secondary abscess

›Amputation

›Reserved for advanced unresponsive eumycetoma

›Amputation rate 3 to 15% in published series

›Multidisciplinary decision with patient

Secondary infection management

›Secondary bacterial infection treatment

›Broad-spectrum empiric antibiotics for sepsis

›Piperacillin-tazobactam 4.5 g IV every 6 hours

›Adjust based on cultures and sensitivities

›Wound care

›Regular dressing changes

›Debridement of infected sinus tracts

›Source control

›Drainage of secondary abscess

›Surgical involvement when needed

09Special Populations/sp47

Pregnancy

›Pregnancy considerations

›Treatment safety profile

›Itraconazole is teratogenic: avoid in pregnancy (Category D/X)

›Postpone elective surgical excision until after delivery when possible

›Co-trimoxazole: avoid in first trimester and near term

›Amikacin: potential ototoxicity to fetus, avoid if alternative available

›Imaging approach

›Ultrasound preferred for lesion assessment during pregnancy

›MRI without gadolinium acceptable if clinically necessary

›Plain radiograph with shielding only when benefit outweighs risk

›Management strategy

›Defer antifungal therapy for eumycetoma until postpartum if stable

›Secondary bacterial infection treated with beta-lactams when possible

›Multidisciplinary input: infectious disease, obstetrics

Geriatric

›Older adult considerations

›Pharmacokinetic changes

›Reduced renal clearance: amikacin dose adjustment essential

›Extended drug half-life increases toxicity risk

›Polypharmacy and drug interaction review for itraconazole (CYP3A4)

›Comorbidity impact

›Diabetes mellitus increases infection severity

›Renal impairment limits amikacin dosing

›Hepatic disease complicates itraconazole use

›Functional considerations

›Lower limb mycetoma disproportionately impairs mobility

›Fall risk with deformity or amputation

10Background/b90

Epidemiology

›Global burden

›WHO neglected tropical disease classification since 2016

›Concentrated in low- and middle-income countries

›Limited global surveillance data

›Geographic distribution

›Mycetoma belt: tropical and subtropical zones between 15 degrees south and 30 degrees north latitude

›Sudan has highest reported burden

›Endemic also in India, Mexico, Senegal, Ethiopia, Chad, Somalia, Yemen

›Population demographics

›Male predominance: male-to-female ratio 2.5 to 3:1

›Peak incidence age 15 to 45 years

›Rural agricultural workers 73% of cases

›Causative organisms

›Eumycetoma (fungal)

›Madurella mycetomatis most common globally

›Trematosphaeria mansoni second most common

›Over 70 causative organisms identified in total

›Actinomycetoma (bacterial)

›Nocardia brasiliensis: most common in Latin America

›Actinomadura madurae: common in Africa and Asia

›Streptomyces somaliensis: Sub-Saharan Africa

›Nocardia asteroides and other Nocardia spp

›Outcomes and complications

›Amputation rates 3 to 15% in published series

›Recurrence rate 10 to 27.5% following treatment

›Therapy dropout rate approximately 55% in some cohorts

›Eumycetoma cure rates 25 to 75% depending on regimen and lesion size

›Actinomycetoma cure rates up to 90% with optimal therapy

Pathophysiology

›Inoculation and local infection

›Entry mechanism

›Traumatic inoculation through skin breach

›Thorn, splinter, or minor injury in contact with soil

›Foot and lower leg most common sites (70% of cases)

›Grain formation

›Organism aggregates into characteristic grains within host tissue

›Grains are colonies of organisms embedded in matrix

›Grain morphology is species-specific

›Host response

›Granulomatous reaction surrounding grain clusters

›Chronic suppuration with sinus tract development

›Minimal systemic immune response in uncomplicated cases

›Progression and tissue destruction

›Local spread along tissue planes

›Fascial planes allow spread beyond initial site

›Direct extension to underlying bone in 28% of cases

›Periosteal reaction followed by cortical erosion and medullary cavity invasion

›Bone involvement mechanism

›Direct invasion rather than hematogenous

›Osteolytic lesions with periosteal new bone formation

›Joint involvement in contiguous spread

›No spontaneous resolution

›No case of spontaneous cure ever reported

›Progressive destruction without treatment is universal

›Eumycetoma versus actinomycetoma differences

›Eumycetoma characteristics

›More indolent progression

›Lower treatment cure rates

›Higher rates of surgical failure without prolonged antifungal support

›Actinomycetoma characteristics

›More aggressive bone invasion earlier in disease course

›Better treatment response to antibacterial combination therapy

›Surgery rarely needed

Therapeutic Considerations

›Treatment strategy principles

›Medical-surgical combination for eumycetoma

›Antifungal therapy must precede surgical excision

›Surgery alone has unacceptable recurrence rate up to 90%

›Post-surgical antifungal continuation mandatory

›Medical-only approach for actinomycetoma

›Antibacterial combination therapy curative in most cases

›Cycle-based amikacin protocol allows toxicity recovery intervals

›Surgical intervention rarely required

›Prognostic determinants

›Lesion size at presentation

›Small lesions: strongest predictor of cure (OR 10.09)

›Large lesions: higher amputation risk and treatment failure

›Bone involvement

›Significantly worsens prognosis

›Increases amputation risk

›Treatment adherence

›Regular follow-up: second strongest predictor of cure (OR 6.81)

›Long duration (months to years) challenges adherence

›Prevention considerations

›Primary prevention

›Protective footwear during outdoor agricultural work

›Protective clothing to avoid skin trauma

›Community education in endemic regions

›Secondary prevention

›Early presentation and diagnosis for smaller lesion size at treatment

›Community awareness programs: 96% of surveyed endemic villagers had poor knowledge

›Psychosocial support to maintain treatment adherence

11Patient Discharge Instructions/pdi33

copy discharge instructions

›Mycetoma home care instructions

›Medications as prescribed

›Take itraconazole with food every time for best absorption

›Take co-trimoxazole as prescribed for full cycle duration

›Do not stop medications early even if the lesion looks better

›Wound care

›Keep draining sinuses clean and covered with dressing

›Change dressings as instructed

›Save any visible grain discharge in a clean container for doctor review

›Activity and footwear

›Wear closed protective shoes or boots at all times outdoors

›Avoid walking barefoot especially on soil or in fields

›Protect the affected limb from further trauma

›Warning signs to return to hospital immediately

›Fever with chills and feeling very unwell

›Rapid increase in swelling, redness, or pain in the lesion

›Red streaks spreading from the lesion (cellulitis spreading)

›Yellow skin or eyes, dark urine (jaundice from liver side effect)

›Decreased hearing or ringing in ears (if taking amikacin)

›Decreased urine output (kidney side effect of amikacin)

›New lesions appearing elsewhere on the body

›Inability to walk or use the affected limb

›Follow-up expectations

›Regular appointments every 4 to 6 weeks during active treatment

›Blood tests for liver and kidney function as scheduled

›Hearing test during amikacin treatment intervals

›Treatment will last at minimum 12 months and often longer

12References/r29

Guidelines and key sources

›Primary guideline references

›WHO Neglected Tropical Diseases: Mycetoma fact sheets and action plans

›Recognized as neglected tropical disease since 2016

›Zijlstra EE et al. Mycetoma: A Unique Neglected Tropical Disease. Lancet Infectious Diseases 2016

›Comprehensive clinical review covering epidemiology, diagnosis, and management

›Verma P, Jha A. Mycetoma: Reviewing a Neglected Disease. Clinical and Experimental Dermatology 2019

›Epidemiology, risk factors, treatment outcomes

›Key clinical trials and studies

›Fahal AH et al. Fosravuconazole versus itraconazole in eumycetoma. Lancet Infectious Diseases 2024

›Phase 2 randomized double-blind proof-of-concept trial in Sudan

›Fosravuconazole 200 mg once weekly comparable to daily itraconazole

›Chandler DJ et al. MASS expert panel. Development of MASS scale. Lancet Infectious Diseases 2025

›International Delphi consensus for clinical severity scoring

›Sow D et al. Mycetoma epidemiology in Senegal 2008-2018. PLoS One 2020

›Three-hospital retrospective study, outcomes and prognostic factors

›Enbiale W et al. Mycetoma as major cause of limb amputation in Ethiopia. PLoS NTD 2026

›Facility-based retrospective study on amputation burden

›Molecular and diagnostic references

›Siddig EE et al. Molecular biological identification tools for mycetoma. Acta Tropica 2022

›Update on PCR and sequencing methods for species identification

›Bahar ME et al. Mycetoma imaging: the best practice. Trans R Soc Trop Med Hyg 2021

›MRI dot-in-circle sign and imaging protocol guidance

›Queiroz-Telles F et al. Neglected Endemic Mycoses. Lancet Infectious Diseases 2017

›Differential diagnosis and comparison with related endemic mycoses

›Coding standards

›ICD-10 B47.0 Eumycetoma

›ICD-10 B47.1 Actinomycetoma

Evidence & Review

Evidence & Review