What are the common skin manifestations in immunocompromised patients, including those with HIV/AIDS, organ transplant recipients, cancer patients undergoing chemotherapy, and individuals with primary immunodeficiency diseases?

Skin Manifestations of Immunocompromised State

Overview and Diagnostic Approach

Immunocompromised patients present with a broad spectrum of skin manifestations that include both infectious and non-infectious etiologies, and early biopsy or aspiration is mandatory because seemingly innocuous lesions may represent life-threatening systemic infections. 1

The differential diagnosis extends far beyond typical infections and must include:

• Drug eruptions from immunosuppressive medications 1
• Cutaneous infiltration with underlying malignancy 1
• Chemotherapy or radiation-induced reactions 1
• Graft-versus-host disease in allogeneic transplant recipients (typically 2-6 weeks post-transplant, presenting as skin rash with diarrhea) 1
• Sweet syndrome (tender red inflammatory nodules/papules on upper limbs, face, or neck) 1, 2
• Erythema multiforme 1
• Leukocytoclastic vasculitis 1

Infectious Manifestations

Bacterial Infections

Bacterial skin infections in immunocompromised patients range from opportunistic organisms to aggressive presentations of common pathogens, requiring immediate broad-spectrum empirical coverage with vancomycin PLUS an antipseudomonal beta-lactam. 3, 4

Key bacterial presentations include:

• Ecthyma gangrenosum: Begins as painless erythematous macules that rapidly become painful and necrotic within 12-24 hours, classically associated with Pseudomonas aeruginosa bacteremia 2
• Nocardia infections: Present as painless subcutaneous nodules or abscesses described as "cold to the touch," often representing metastatic foci from pulmonary sources 1, 5
• Atypical mycobacterial infections: Opportunistic cutaneous involvement 1, 5
• Recurrent staphylococcal infections: Particularly "transplant elbow" in renal transplant recipients 5

Fungal Infections

Cutaneous mold infections occur frequently in patients with cellular immune deficiency and may represent disseminated disease, primary inoculation, or infection at previous IV line sites. 1

Common fungal manifestations include:

• Aspergillus, Mucormycosis, Scedosporium, and Fusarium species: Present as papules, nodules, ulcers, or with ecthyma gangrenosum appearance 1
• Cryptococcus neoformans: Opportunistic infection in severely immunosuppressed patients 5
• Extensive confluent dermatophyte infections: More widespread and severe than in immunocompetent hosts 5, 6
• Candidiasis: Occurs in 47% of AIDS patients 6

For Aspergillus, Scedosporium, and Fusarium infections, voriconazole is the best therapeutic option, with amphotericin B as an excellent alternative and posaconazole as a reasonable option in combination or for transition to oral therapy. 1

Viral Infections

Varicella zoster virus (VZV) is one of the two most frequent herpesviruses causing cutaneous infection in immunosuppressed patients, with 25-45% developing dermatomal zoster and 10-20% risk of dissemination without prompt antiviral therapy. 1

Viral presentations include:

• Herpes zoster: Unilateral vesicular eruption with dermatomal pain preceding skin findings by 24-72 hours, most common in first year post-transplant or chemotherapy 1
• Disseminated VZV: May mimic atypical varicella or present with nonspecific non-vesicular lesions 1
• Herpes simplex virus (HSV): Chronic poorly healing ulcers without vesicular component, making clinical diagnosis difficult 1
• Molluscum contagiosum: Seen in 9% of AIDS patients 6
• Extensive papillomavirus infections: May undergo malignant transformation, particularly at genital sites 7

Eczema herpeticum requires high-dose IV acyclovir in immunocompromised patients before considering systemic immunosuppressive therapy. 3

Parasitic Infections

Cutaneous leishmaniasis can present with atypical, multifocal lesions in immunocompromised patients, with purulence only occurring with secondary bacterial infection. 2

Non-Infectious Manifestations

Malignancies

Immunosuppressed patients, particularly organ transplant recipients, have dramatically increased risk of aggressive nonmelanoma skin cancers (NMSCs) with subclinical extension far beyond conventional surgical margins. 1, 8

Key malignancy considerations:

• Squamous cell carcinoma (SCC): Most common malignancy in transplant recipients, behaves more aggressively with higher recurrence rates 1, 7
• Basal cell carcinoma: Increased incidence but less common than SCC in this population 7, 9
• Kaposi sarcoma: Increased risk particularly in renal transplant recipients; when presenting as intra-abdominal disease, usually has concurrent skin manifestations 1, 7
• Aggressive subclinical extension: SOTRs have 2.74 times the odds of NMSC with aggressive subclinical extension compared to non-SOTRs 8
• Malignant melanoma: Higher morbidity and mortality in HIV-infected patients 9

Solid organ transplant recipients with multiple tumors, frequent development, or aggressive features (extension beyond cutaneous structures, perineural involvement, large poorly differentiated tumors) require urgent diagnosis and treatment. 1

Inflammatory and Drug-Related Conditions

• Seborrheic dermatitis: Occurs in 32% of AIDS patients 6
• Acquired ichthyosis or xerosis: Present in 30% of AIDS patients, more common in those with AIDS versus AIDS-related complex 6
• Pyoderma gangrenosum: Begins as erythematous papules/pustules rapidly progressing to deep excavating ulcerations with sterile purulent material, often preceded by trauma 2

Critical Management Principles

Immediate Diagnostic Steps

Biopsy or aspiration of skin lesions must be implemented as an early diagnostic step to obtain material for histological and microbiological evaluation, as seemingly localized lesions may represent systemic or life-threatening infections. 1

Essential investigations include:

• Culture of purulent material for bacteria and fungi 2
• Skin biopsy from lesional edge for histopathology and direct immunofluorescence 2
• Blood cultures if systemic signs present (fever >38°C, heart rate >90, respiratory rate >24, spreading erythema >5 cm) 3, 2
• Complete blood count to assess for neutropenia 2

Empirical Antimicrobial Therapy

Empiric antimicrobial therapy must be initiated immediately based on underlying disease, primary immune defect, morphology of skin lesions, prior antimicrobial prophylaxis, and local resistance patterns. 1

For bacterial infections of unknown etiology:

• Vancomycin (30-60 mg/kg/day targeting trough 15-20 μg/mL) PLUS antipseudomonal beta-lactam (cefepime, meropenem, or piperacillin-tazobactam) 4
• De-escalate after 48-72 hours based on culture results and clinical response 3, 4
• Never use Bactrim monotherapy empirically as it leaves dangerous gaps in coverage for Pseudomonas, Streptococcus, and anaerobes 4

Surgical Considerations

Surgical debridement is crucial for obtaining cultures and sensitivities and is necessary to remove devitalized tissue and promote healing, particularly for Nocardia and fungal infections. 1

For NMSCs in immunosuppressed patients, destructive therapies (curettage & electrodessication, cryotherapy) may be preferred for clinically low-risk tumors due to ability to treat multiple lesions at a single visit. 1

Population-Specific Considerations

HIV/AIDS Patients

HIV-infected patients with normal CD4 count (>200 cells/mm³) have mortality and morbidity rates similar to the general population, while worse perioperative outcomes occur with lower CD4 counts and higher viral loads. 1

CD4 count and viral load should always be measured in HIV/AIDS patients undergoing emergency procedures to predict postoperative complications. 1

Organ Transplant Recipients

Up to 50% of intestinal perforations in kidney transplant patients occur in the first three months post-transplant, and small bowel lymphoma may occur in up to 46% of transplanted patients on high-dose immunosuppressants. 1

Cancer Patients on Chemotherapy

Leukemic patients with bacteremic gram-negative infection may develop metastatic skin lesions, and the intensity of immune defect diminishes dermatological findings, making localized lesions potentially represent systemic infections. 1, 5

Common Pitfalls to Avoid

• Delaying broad-spectrum antibiotics while awaiting culture results can lead to rapid deterioration 4
• Failing to biopsy suspicious lesions early due to altered immune response masking severity 1
• Underestimating malignancy risk and failing to biopsy actinic keratoses with atypical appearance or non-response to therapy 1
• Using narrow empirical regimens that fail to cover resistant organisms and opportunistic pathogens 4
• Discontinuing antiretroviral therapy unnecessarily in HIV patients requiring surgery 1