What is causing a 6-year-old child with a history of retinoblastoma and eye enucleation, who has undergone 6 months of chemotherapy, to experience frequent infections, including recurrent streptococcal (strep) pharyngitis and skin sloughing in the genital area?

Post-Chemotherapy Immunodeficiency with Recurrent Infections and Genital Skin Sloughing

This 6-year-old child is experiencing chemotherapy-induced immunodeficiency with recurrent bacterial infections and likely Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), which requires immediate medical evaluation and discontinuation of any recently started medications.

Understanding the Clinical Picture

Chemotherapy-Induced Immune Dysfunction

This child's presentation reflects profound and persistent immunosuppression following cancer treatment:

• All children have some degree of immune dysfunction at completion of chemotherapy, with persistent abnormalities documented at 6 months post-therapy including leukopenia (25%), neutropenia (15%), hypogammaglobulinemia (25%), and abnormal lymphocyte function (25%) 1
• Chemotherapy significantly lowers antibody levels against vaccine-preventable diseases, with 6% losing protection against measles/mumps, 18-25% against polio, and 21% against diphtheria 2
• The immune system remains compromised for months after completing treatment, leaving children vulnerable to bacterial, viral, and fungal infections 3, 1

Recurrent Streptococcal Pharyngitis

The two documented strep throat episodes in recent months indicate:

• Inadequate immune response to clear and develop lasting immunity against Group A Streptococcus 1
• Possible treatment failure or reinfection due to immunocompromised state 3
• Not a chronic carrier state, as the child is symptomatic with documented infections 3

Critical Concern: Genital Skin Sloughing

Immediate Differential Diagnosis

The genital skin sloughing is the most alarming finding and suggests:

Primary concern - Drug reaction:

• Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) from antibiotics used to treat the strep infections (most commonly sulfonamides, penicillins, or cephalosporins) 3
• These are life-threatening mucocutaneous reactions requiring immediate hospitalization

Secondary considerations in immunocompromised children:

• Disseminated bacterial or fungal infection with cutaneous manifestations, particularly in neutropenic patients 3
• Ecthyma gangrenosum from Pseudomonas or other gram-negative organisms, though typically presents as necrotic lesions rather than sloughing 3
• Severe candidiasis affecting mucocutaneous areas in profoundly immunosuppressed patients 3

Immediate Management Algorithm

Step 1: Emergency Assessment (Within Hours)

• Stop all recently started medications immediately, particularly antibiotics 3
• Examine for mucosal involvement (oral, ocular, genital) and calculate body surface area affected 3
• Obtain complete blood count to assess for neutropenia (absolute neutrophil count <500 cells/mm³ indicates high risk) 3
• Culture the affected skin and blood if febrile or systemically ill 3

Step 2: Risk Stratification

High-risk features requiring hospitalization:

• Skin sloughing >10% body surface area 3
• Mucosal involvement in multiple sites 3
• Neutropenia (<500 cells/mm³) 3
• Fever or systemic signs of infection 3

If high-risk features present:

• Admit to hospital immediately for supportive care and infection monitoring 3
• Start broad-spectrum antibiotics covering MRSA and gram-negative organisms (vancomycin plus piperacillin-tazobactam or carbapenem) if neutropenic with fever 3
• Consult dermatology for skin biopsy if diagnosis uncertain 3

Step 3: Infection Prevention Strategy

For recurrent streptococcal infections:

• Do NOT use antibiotic prophylaxis for preventing recurrent strep throat, as it is not effective and promotes resistance 3
• Ensure proper treatment duration (10 days of penicillin or amoxicillin) for each documented strep infection 3
• Consider household contacts as potential sources of reinfection, though routine testing/treatment is not recommended 3

For overall immunodeficiency management:

• Avoid live vaccines until at least 3 months post-chemotherapy (6 months if anti-B-cell antibodies were used) 3
• Consider TMP-SMX prophylaxis if not already prescribed, as it reduces bacterial infections and provides protection against Pneumocystis 3
• Check immunoglobulin levels and consider IVIG replacement if IgG <400 mg/dL with recurrent infections 3

Step 4: Revaccination Planning

Once acute issues resolve:

• Begin revaccination at 3 months post-chemotherapy with inactivated vaccines 3
• Check antibody titers for vaccine-preventable diseases before revaccinating to guide which vaccines are needed 3, 2
• Expect suboptimal responses initially; some children may require additional doses 2

Critical Pitfalls to Avoid

• Never dismiss skin sloughing as a minor issue in an immunocompromised child—this requires urgent evaluation 3
• Do not continue antibiotics if drug reaction is suspected; the risk of progression to TEN is life-threatening 3
• Avoid prophylactic antibiotics for strep throat prevention, as this promotes resistance without proven benefit 3
• Do not assume immune recovery at 6 months post-chemotherapy; persistent defects are common and require ongoing monitoring 1
• Never administer live vaccines during or within 3 months of completing chemotherapy 3

Follow-up Monitoring

• Document all infections meticulously including symptoms, physical findings, culture results, and treatments 4
• Reassess immune function at 6 months post-chemotherapy with CBC, immunoglobulin levels, and lymphocyte subsets 1
• Screen for vaccine-preventable disease susceptibility through antibody titers before exposure risks (school, daycare) 3, 2