How to differentiate between fungal infections and amyopathic dermatomyositis (ADM)?

Differentiating Fungal Infections from Amyopathic Dermatomyositis (ADM)

Skin biopsy with histopathology and fungal staining is the definitive method to distinguish fungal infections from ADM, as fungal elements will be visible with PAS, Grocott's methenamine silver, or calcofluor white stains in fungal disease but absent in ADM, while ADM shows characteristic pathognomonic cutaneous features including heliotrope rash and Gottron's papules. 1, 2

Primary Diagnostic Approach

Step 1: Examine for Pathognomonic Cutaneous Features

ADM-specific findings (if present, strongly favor ADM):

• Heliotrope rash: Violaceous or erythematous discoloration of the upper eyelids—this is pathognomonic for dermatomyositis 2
• Gottron's papules: Erythematous to violaceous papules over extensor surfaces of joints (MCPs, PIPs, elbows, knees) 2, 3
• Gottron's sign: Erythematous macules in same distribution without papules 2
• Periungual telangiectasias and nailfold capillary changes 2
• Poikiloderma in photodistributed areas (face, neck, upper chest, back—sparing groin and axillae) 2, 4

Fungal infection features:

• Greasy, yellow-white scales (especially in seborrheic distribution) 2
• Involvement of nasolabial folds, scalp, eyebrows, ears, central chest, and intertriginous areas 2
• Necrotic lesions during granulocytopenia suggest mold infection 1

Step 2: Assess Distribution Pattern

• ADM: Photodistributed (sun-exposed areas), spares groin and axillae 2
• Fungal (cutaneous): Seborrheic distribution (nasolabial folds, scalp, intertriginous areas) or disseminated in immunocompromised hosts 1, 2

Step 3: Evaluate Scale Characteristics

• ADM: Minimal scaling with prominent erythema and violaceous discoloration 2
• Fungal: Greasy, yellow-white scales (seborrheic dermatitis pattern) or variable depending on organism 2

Definitive Diagnostic Testing

Histopathology with Fungal Staining (Gold Standard)

Biopsy specimens should be taken from suspected skin lesions when clinically feasible 1:

• Fungal stains required: Periodic acid-Schiff (PAS), Grocott's methenamine silver, or optical brighteners (calcofluor white) 1
• Fungal elements may be misinterpreted as artifacts with routine Gram or H&E staining 1
• Grocott staining best visualizes non-vital fungal structures 1
• Presence of hyphae, yeast, or fungal elements confirms fungal infection 1
• Absence of fungal elements with interface dermatitis pattern supports ADM 2

Laboratory Evaluation for ADM

To confirm ADM, the following must be documented 2, 4, 5:

Muscle enzyme assessment (must remain normal for ≥6 months):

• Creatine kinase (CK) 2
• Aldolase 2
• AST and ALT 2

Myositis-specific autoantibodies (may be present):

• Anti-Jo-1, anti-Mi-2, anti-TIF1-gamma 2

Muscle imaging and electrophysiology (must be normal):

• EMG should show no myopathic changes 2
• MRI of proximal muscles should show no inflammation 2

Fungal-Specific Testing

For suspected invasive fungal disease 1:

• Culture from tissue biopsies or sterile body fluids (definitive diagnosis) 1
• Aspergillus galactomannan ELISA (twice weekly screening in high-risk patients) 1
• 1,3-β-D-glucan (BG) screening in high-risk hematological patients 1
• Cryptococcus antigen testing in CSF with India ink preparation 1
• Molecular methods (Aspergillus PCR) show high sensitivity/specificity but not yet standardized 1

Clinical Context Considerations

Risk Factors Favoring Fungal Infection

• Prolonged granulocytopenia 1
• Antibiotic-refractory fever 1
• Immunocompromised state (hematologic malignancy, transplant) 1
• Pulmonary infiltrates during antibiotic treatment 1

Systemic Manifestations

If systemic involvement present:

• Imaging with CT or MRI for suspected invasive fungal disease of lungs, liver, spleen, GI tract, CNS 1
• High-resolution chest CT for interstitial lung disease screening in ADM 2
• The "reversed halo sign" on CT is more suggestive of mucormycosis than aspergillosis 1

Critical Screening After ADM Diagnosis

Once ADM is confirmed, mandatory screening includes 2, 3:

• High-resolution chest CT for interstitial lung disease (75% of ADM patients have radiographic evidence of interstitial fibrosis) 4
• Age-appropriate cancer screening (25-33% develop associated malignancies, most commonly breast, ovarian, nasopharyngeal, bladder) 2, 3

Common Pitfalls

• Do not rely on clinical symptoms alone—both conditions have non-specific presentations 1
• Skin infiltrations during pancytopenia may be misinterpreted as thrombocytopenic purpura but could represent fungal infection 1
• 18.75% of ADM patients develop muscle weakness within 5 years, requiring ongoing monitoring 4
• Fungal elements may be missed without special stains—always request PAS, Grocott's, or calcofluor white 1
• Some ADM patients have subclinical muscle disease detectable only by MRI or EMG 5