Lymphocytic Interstitial Pneumonia (LIP): Symptoms, Diagnosis and Treatment

What is lymphocytic interstitial pneumonia?

Lymphocytic interstitial pneumonia (LIP) is a rare form of interstitial lung disease in which lymphocytes (a type of white blood cell) build up in the walls between the air sacs of the lung. This thickens the lung tissue, can create thin-walled air cysts, and gradually makes it harder for oxygen to pass into the blood.

LIP is rarely an isolated illness. In most adults it occurs alongside another condition that affects the immune system, most commonly Sjogren's syndrome, and less often HIV infection, other autoimmune diseases or antibody deficiency. In children, LIP is classically associated with HIV. When no cause is found it is called idiopathic LIP, which is very uncommon.

Because LIP sits on a spectrum of lymphocyte-driven lung disease, a careful diagnosis is needed to separate it from low-grade lymphoma of the lung. Care is usually shared between the pulmonologist and rheumatology, infectious disease or haematology teams, depending on the underlying cause.

Symptoms of LIP

LIP usually develops slowly over months or years. Some people have no symptoms and the condition is found on a scan done for another reason. When symptoms occur they include:

• Breathlessness: gradually increasing, first on exertion.
• Dry cough: persistent and not relieved by cough syrups or antibiotics.
• General symptoms: tiredness, weight loss, low-grade fever or joint pains, which may reflect the associated condition.
• Features of Sjogren's syndrome: dry eyes, dry mouth or swelling of the salivary glands.

Crackles may be heard on listening to the chest, and finger clubbing is occasionally present in advanced disease.

Causes and associated conditions

LIP is thought to result from an exaggerated immune response in which lymphocytes accumulate in lung tissue. Recognised associations include:

• Sjogren's syndrome, the most frequent association in adults
• Other autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease
• HIV infection, particularly in children
• Common variable immunodeficiency and other antibody deficiency states
• Certain viral infections, including Epstein-Barr virus
• Some medicines and, rarely, bone marrow transplantation

LIP is more common in women, reflecting the female predominance of Sjogren's syndrome. It is not contagious.

How LIP is diagnosed

Diagnosis combines the clinical picture, high-resolution CT and, in many cases, tissue sampling. The aim is to confirm LIP, identify any underlying condition and exclude lymphoma and infection.

A bronchoscopy is often the first invasive step. Where the CT shows enlarging nodules or other worrying features, a larger surgical lung biopsy may be needed so that lymphoma can be ruled out with confidence. Cases are ideally reviewed in a multidisciplinary meeting with radiology and pathology.

Treatment of LIP

Treatment depends on symptoms, the degree of lung involvement and the underlying cause. People with mild, stable disease and no symptoms may simply be monitored.

Treating the associated condition

Controlling the underlying disease is central. This may mean treatment of Sjogren's syndrome or another autoimmune disease with rheumatology, antiretroviral therapy for HIV, or immunoglobulin replacement for antibody deficiency.

Anti-inflammatory therapy

For symptomatic or progressive LIP, oral corticosteroids are the usual first treatment. When disease does not respond or relapses as steroids are reduced, steroid-sparing immunosuppressants such as azathioprine or mycophenolate, or the B-cell therapy rituximab, may be used.

Supportive care

Pulmonary rehabilitation, vaccination against influenza and pneumococcal disease, smoking cessation and oxygen therapy where needed all help. Cysts do not shrink with treatment, but the inflammation around them often does.

Outlook and follow-up

The course of LIP varies. Many patients improve or stabilise with treatment, while a minority develop progressive fibrosis. A small proportion transform to lymphoma over time, which is why long-term follow-up matters.

Follow-up usually includes regular lung function tests, periodic CT scans and review of any new symptoms such as weight loss, night sweats or enlarging nodules. Coordinated review with the rheumatology or immunology team keeps the underlying condition under control.

When to seek urgent care

Seek medical attention promptly for breathlessness at rest or a rapid worsening of breathing, high fever with cough while on immunosuppressive treatment, chest pain, coughing up blood, or blue lips. Patients taking steroids or immunosuppressants are at higher risk of infection and should not delay assessment.

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