Can Chronic Lymphocytic Leukemia (CLL) cause skin lesions?

Skin Manifestations in Chronic Lymphocytic Leukemia

Yes, Chronic Lymphocytic Leukemia (CLL) can cause various skin lesions, occurring in up to 25% of CLL patients. 1 These cutaneous manifestations can be broadly categorized into direct leukemic infiltration of the skin (leukemia cutis) and non-malignant secondary skin disorders.

Types of Skin Lesions in CLL

1. Leukemia Cutis (Direct Infiltration)

• Presents as solitary, grouped, or generalized papules, plaques, nodules, or large tumors 1
• Most commonly affects the trunk and extremities 2
• Clinical appearance varies:
  • Papulonodular lesions are the most common presentation 3
  • Can also manifest as macules, plaques, and ulcers 2
• Head and neck are frequently involved areas 3

2. Secondary Non-Malignant Skin Disorders

• Infectious manifestations: CLL patients have increased susceptibility to skin infections
• Hemorrhagic manifestations: Purpura and petechiae due to thrombocytopenia
• Inflammatory reactions:
  • Vasculitis
  • Generalized pruritus
  • Exfoliative erythroderma
  • Paraneoplastic pemphigus
  • Eosinophilic dermatosis of hematologic malignancy 4
• Exaggerated reactions to insect bites and insect bite-like reactions 1

Secondary Skin Malignancies in CLL

CLL patients have an eightfold higher risk of developing skin cancers compared to the general population 1. This increased risk may be associated with:

• Immune dysfunction from CLL itself
• Effects of treatment with alkylating agents and purine analogs 1
• Ongoing immunosuppression

Diagnostic Approach

When skin lesions appear in a CLL patient:

1. Skin biopsy is essential for definitive diagnosis
2. Immunohistochemistry to confirm leukemic infiltration and differentiate from other skin conditions
3. Correlation with disease status (active disease vs. remission)

Prognostic Implications

• Leukemia cutis in CLL generally has a good prognosis and many authors suggest it doesn't significantly affect survival 1
• Poor prognosis is associated with:
  • Blastic transformation (Richter's syndrome)
  • Leukemic skin infiltrations appearing after the initial CLL diagnosis 1

Management Approaches

Treatment depends on the type of skin manifestation and extent of disease:

For Leukemia Cutis:

• Early-stage localized disease: Observation alone may be sufficient, especially in older patients 3
• Advanced or symptomatic disease: Systemic therapy, particularly in younger patients 3
• For resistant or recurrent skin infiltrations: Local radiotherapy can be effective 2

For Secondary Skin Manifestations:

• Treat underlying CLL if active
• Manage specific conditions appropriately (e.g., antibiotics for infections, topical steroids for inflammatory conditions)

Important Considerations

• Isolated cutaneous CLL is rare and may be diagnosed late 5
• CLL skin involvement at sites of previous herpes infection is relatively common 3
• In most patients, resolution of cutaneous infiltrations occurs simultaneously with hematologic remission 2
• Young patients (≤60 years) typically present with early-stage disease, while advanced-stage disease is more common in patients >60 years 3

Dermatologic monitoring should be part of routine follow-up for CLL patients given their increased risk of skin manifestations and secondary skin malignancies.