Diagnosis: Erythema Multiforme with Possible Mycoplasma Pneumoniae Infection
The clinical presentation of bilateral lower extremity target lesions with crusted centers combined with cold and cough symptoms in an immunocompromised patient most likely represents erythema multiforme, potentially triggered by an atypical respiratory infection such as Mycoplasma pneumoniae, though opportunistic infections must be urgently excluded through aggressive diagnostic workup.
Immediate Diagnostic Approach
Skin Lesion Evaluation
- Obtain skin biopsy immediately from representative target lesions for histopathological examination, microbial staining (Gram stain, fungal stains), and cultures (bacterial, fungal, viral) 1
- The early identification of an etiologic agent is essential in immunocompromised hosts because microbial resistance makes empiric treatment regimens difficult and potentially dangerous 1
- Skin lesions, no matter how small or innocuous in appearance, should be carefully evaluated with early involvement of dermatology and infectious diseases specialists 1
Respiratory Assessment
- Obtain chest imaging immediately - start with portable chest radiograph, but proceed to CT scan if standard radiograph is negative and clinical suspicion remains high 1, 2
- CT imaging is particularly valuable in immunocompromised patients for detecting small nodular or cavitary lesions characteristic of opportunistic pathogens that are difficult to detect on standard chest radiographs 1, 2
- Obtain two sets of blood cultures before initiating antibiotics 2
- Collect respiratory specimens (expectorated sputum or deep tracheal aspirate if intubated) for Gram stain, culture, and viral testing 2
Risk Stratification by Immune Status
- Determine CD4+ lymphocyte count if HIV-infected to guide differential diagnosis 1, 2
- CD4+ >200 cells/μL with no systemic symptoms: unlikely to have opportunistic infections; consider common community-acquired pathogens 1, 2
- CD4+ <200 cells/μL OR CD4+ >200 with unexplained fever, weight loss, or thrush: suspect Pneumocystis jirovecii, tuberculosis, and other opportunistic infections 1, 2
- Assess neutrophil count and duration of neutropenia if applicable 1
Differential Diagnosis Considerations
Infectious Etiologies in Immunocompromised Hosts
The differential diagnosis is broader than in immunocompetent patients and includes 1:
- Bacterial: Pseudomonas aeruginosa (can cause folliculitis progressing to ecthyma gangrenosum), Staphylococcus aureus, Streptococcus species
- Fungal: Aspergillus species (can cause disseminated cutaneous lesions), Cryptococcus, endemic fungi
- Viral: Herpes simplex virus, varicella-zoster virus, cytomegalovirus
- Atypical pathogens: Mycoplasma pneumoniae (classic trigger for erythema multiforme with respiratory symptoms)
Non-Infectious Etiologies
Consider 1:
- Drug eruption (review all medications)
- Chemotherapy- or radiation-induced skin reactions
- Graft-versus-host disease (if transplant recipient)
- Sweet syndrome
- Leukocytoclastic vasculitis
Empirical Treatment Strategy
Broad-Spectrum Antimicrobial Coverage
Initiate immediate empirical therapy with vancomycin PLUS an antipseudomonal beta-lactam 3:
- Vancomycin: 30-60 mg/kg/day in divided doses, targeting trough 15-20 μg/mL for MRSA and resistant gram-positive coverage 3
- Antipseudomonal beta-lactam: cefepime, meropenem, or piperacillin-tazobactam for broad gram-negative coverage including Pseudomonas 3
Rationale for Broad Coverage
- Immunocompromised patients are at risk for infections from diverse organisms, including bacteria not typically pathogenic in healthy hosts 3
- Many infections are hospital-acquired with mounting resistance among both gram-positive and gram-negative bacteria, making narrow empirical regimens dangerous 3
- Delaying broad-spectrum antibiotics while awaiting culture results can lead to rapid deterioration 3
Critical Pitfall to Avoid
Do NOT use Bactrim (trimethoprim-sulfamethoxazole) monotherapy empirically - this leaves dangerous gaps in coverage for Pseudomonas, Streptococcus, and anaerobes 3
Specific Considerations for Target Lesions
If Pseudomonas Folliculitis Suspected
- Monitor daily for progression from folliculitis to ecthyma gangrenosum, which requires aggressive IV therapy 4
- Consider ciprofloxacin 400 mg IV every 8 hours for severe disease in immunocompromised patients 4
- Obtain cultures to confirm Pseudomonas aeruginosa and guide susceptibility-directed therapy 4
If Aspergillus Infection Suspected
- Systemic antifungal therapy is the mainstay of treatment 1
- Surgical debridement may be necessary for localized lesions, though it may increase mortality in neutropenic patients 1
- Control predisposing factors by decreasing corticosteroid dosage or awaiting resolution of neutropenia 1
Respiratory Infection Management
Pneumonia Diagnosis Criteria
Diagnose pneumonia when a new pulmonary infiltrate appears on chest imaging combined with any two of three clinical features 2:
- Fever (temperature >37.8°C)
- Leukocytosis or leukopenia
- Purulent respiratory secretions
Bronchoscopy Indications
Perform bronchoscopy with bronchoalveolar lavage when 2:
- Patient cannot produce adequate sputum
- Suspected opportunistic infections
- Pneumonia fails to respond to empiric therapy
- Quantitative cultures needed to distinguish colonization from true infection
Viral Pathogen Testing
Routine testing for noninfluenza respiratory viruses is strongly supported in immunocompromised populations given the high risk of progression from upper respiratory viral infection to fatal pneumonia 2
De-escalation Strategy
After 48-72 hours, reassess based on 3:
- Clinical response to therapy
- Culture and susceptibility results
- Biopsy findings if obtained
- Adjust antibiotics to narrower spectrum based on identified pathogens
If clinical improvement does not occur within 72 hours, reassess diagnosis and consider alternative or combination therapy 4