What is the best course of treatment for a post liver transplant patient presenting with multiple maculopapular skin lesions with central necrosis?

Multiple Maculopapular Skin Lesions with Central Necrosis in Post-Liver Transplant Patient

This patient requires immediate dermatology and infectious disease consultation with urgent skin biopsy and empiric broad-spectrum antimicrobial therapy covering disseminated fungal infection, particularly invasive molds like Aspergillus, Fusarium, and Mucor species, which are life-threatening in immunocompromised transplant recipients. 1

Immediate Diagnostic Approach

Obtain urgent skin biopsy with both tissue culture and histopathology to differentiate between disseminated fungal infection and other etiologies, as this is crucial for cultures, sensitivities, and removal of devitalized tissue. 1 The presence of central necrosis in multiple lesions is highly concerning for:

Most Likely Infectious Etiologies in This Population:

• Fusarium species: Present with multiple erythematous macules with central pallor that rapidly evolve to papules and necrotic nodules, often with a ring of erythema surrounding central necrosis, preferentially on extremities. Blood cultures are positive in 40-50% of cases when cutaneous lesions appear, and mortality remains high. 1

• Aspergillus species: Cause painful erythematous skin nodules that become necrotic and resemble ecthyma gangrenosum due to angioinvasion. Aspergillus occurs in 10-14% of profoundly immunosuppressed patients with high mortality. 1

• Mucor/Rhizopus species: Produce painful erythematous skin nodules with necrosis, with secondary cutaneous involvement from hematogenous dissemination. 1

• Candida species: Manifest as discrete pink to red papules (0.5-1.0 cm) on trunk and extremities that may develop central pallor or become hemorrhagic if thrombocytopenic. 1

Immediate Management Algorithm

Step 1: Urgent Consultation and Biopsy

• Immediate dermatology consultation for patients with cellular immune defects including organ transplant recipients. 1
• Immediate infectious disease consultation to guide antimicrobial selection. 1
• Perform skin biopsy and surgical debridement early for histopathology, fungal cultures, bacterial cultures, and mycobacterial cultures. 1

Step 2: Empiric Antimicrobial Therapy

In life-threatening situations, initiate empiric antibiotics, antifungals, and/or antivirals immediately while awaiting culture results. 1 The specific regimen should include:

• Broad-spectrum antifungal coverage: Initiate voriconazole or amphotericin B formulation to cover invasive molds (Aspergillus, Fusarium, Mucor). New azole antifungal agents show promise for Fusarium infections. 1

• Antibacterial coverage: Add vancomycin plus antipseudomonal coverage (cefepime, carbapenem, or piperacillin-tazobactam) to cover gram-negative bacteria including Pseudomonas aeruginosa which can cause ecthyma gangrenosum-like lesions. 1, 2

Step 3: Blood Cultures and Additional Workup

• Obtain blood cultures immediately, as Fusarium blood cultures are positive in 40-50% of cases with cutaneous lesions. 1
• Check complete blood count to assess for neutropenia or thrombocytopenia. 1
• Consider chest CT to evaluate for pulmonary involvement with disseminated mold infection. 1

Critical Pitfalls to Avoid

Do not delay empiric antifungal therapy while awaiting biopsy results, as disseminated fungal infections in immunocompromised transplant recipients have extremely high mortality rates. 1

Do not assume this is a cutaneous malignancy (squamous cell carcinoma, basal cell carcinoma) despite the increased risk in liver transplant recipients, as these typically do not present with acute onset of multiple necrotic lesions. 1

Do not overlook the possibility of graft-versus-host disease, which can present with maculopapular eruption and fever 15-19 days post-transplant, though this is rare after liver transplantation and typically does not cause central necrosis. 3

Immunosuppression Considerations

Coordinate with the transplant center before reducing immunosuppression, as this decision must balance infection control against graft rejection risk. 1 Reduction may be necessary for effective treatment of disseminated fungal infection but requires careful monitoring for allograft dysfunction. 1

Differential Diagnosis Considerations

While cutaneous malignancies are the most common de novo malignancies in liver transplant recipients (up to 100 times higher incidence than general population), they typically present 3-5 years post-transplant and do not cause acute multiple necrotic lesions. 1

CMV infection should be considered in the differential, particularly in CMV D+/R- patients, though CMV typically does not present with multiple necrotic skin lesions. 4