Diffuse infiltrative lymphocytosis syndrome

Overview

Diffuse Infiltrative Lymphocytosis Syndrome (DILS) is a rare, chronic inflammatory condition most commonly seen in individuals infected with the human immunodeficiency virus (HIV). It is characterized by persistent infiltration of CD8+ T lymphocytes into various tissues, particularly the salivary glands, leading to symptoms that resemble Sjögren’s syndrome. Unlike other opportunistic infections in HIV, DILS is not caused by a secondary pathogen but rather represents an immune-mediated response associated with HIV infection itself.

Causes

The exact cause of DILS is unknown, but it is strongly associated with untreated or poorly controlled HIV infection. The condition is thought to result from an abnormal immune response in which CD8+ cytotoxic T-cells infiltrate target organs such as the salivary glands, lungs, liver, kidneys, and peripheral nerves. Risk factors include:

• HIV infection: Particularly in the early stages or before antiretroviral therapy (ART).

• Genetic predisposition: Certain HLA types (e.g., HLA-DR5) may increase susceptibility.

• Immune dysregulation: The imbalance of T-cell subsets is central to the pathogenesis.

Symptoms

DILS primarily affects the salivary glands but may involve multiple organ systems. Symptoms can mimic autoimmune conditions like Sjögren’s syndrome. Common features include:

• Bilateral parotid gland enlargement: Painless swelling of the salivary glands is a hallmark sign.

• Dry mouth (xerostomia): Due to lymphocytic infiltration of salivary glands.

• Dry eyes (xerophthalmia): In some cases, due to lacrimal gland involvement.

• Generalized lymphadenopathy: Swollen lymph nodes throughout the body.

• Peripheral neuropathy: Numbness, tingling, or weakness in the limbs.

• Interstitial lung disease: Cough and shortness of breath may occur if the lungs are involved.

• Renal involvement: In rare cases, interstitial nephritis or renal impairment may develop.

Diagnosis

Diagnosis of DILS involves ruling out other causes of glandular swelling and systemic inflammation while confirming CD8+ lymphocyte infiltration. The following steps are typically taken:

• HIV testing: All suspected cases should be evaluated for HIV infection.

• CD4/CD8 ratio: A low CD4 count with elevated CD8 levels is often observed.

• Salivary gland biopsy: Shows marked lymphocytic infiltration, predominantly CD8+ T-cells.

• Imaging: Ultrasound or MRI of the salivary glands can reveal enlargement and inflammation.

• Exclusion of Sjögren’s syndrome: Anti-SSA/Ro and anti-SSB/La antibodies are usually negative in DILS.

Treatment

The cornerstone of DILS treatment is effective antiretroviral therapy (ART), which helps control HIV replication and modulate the immune response. Additional treatments may be required based on symptom severity and organ involvement:

• Antiretroviral therapy: Initiation or optimization of ART typically leads to improvement in glandular swelling and systemic symptoms.

• Corticosteroids: Used in moderate to severe cases to reduce inflammation and lymphocyte infiltration.

• Immunosuppressive agents: Rarely needed but may be considered for resistant or life-threatening organ involvement.

• Symptomatic treatment: Artificial tears and saliva substitutes for dry eyes and mouth, respectively.

• Neuropathy management: Pain relievers, physical therapy, or medications like gabapentin for peripheral nerve symptoms.

Prognosis

With early diagnosis and proper management, particularly with antiretroviral therapy, the prognosis of DILS is generally favorable. Most patients respond well to ART, and glandular swelling and systemic symptoms improve significantly. However, if left untreated, DILS can lead to chronic discomfort, progressive organ dysfunction, or complications from persistent inflammation. Long-term monitoring is essential to assess treatment response and detect potential relapse or progression.