WORKUP

Lab Studies:

• Laboratory tests are nonspecific.

• The most essential items are the chest radiograph, measurement of gas exchange, and histology.

• Serum protein electrophoresis: Polyclonal hypergammaglobulinemia is common.

• Lactate dehydrogenase

• In pediatric patients with LIP and HIV, lactate dehydrogenase (LDH) may be elevated to 300-500 IU/L, approximately half the levels seen in Pneumocystis carinii pneumonia.

• This measurement is not helpful in adults.

• Serologic testing: Test for HIV type 1, HTLV type 1, EBV, and rheumatoid factor.

Imaging Studies:

• Chest radiograph

• Bibasilar interstitial or micronodular infiltrates (see Image 1) with coalescence into an alveolar pattern are present.

• In adults, honeycombing is present in up to one third of cases. Hilar adenopathy and pleural effusion are uncommon.

• Similar infiltrates are seen in children, often with mediastinal widening and hilar enlargement denoting pulmonary lymphoid hyperplasia.

• CT scan

• This reveals the extent of the disease.

• It may demonstrate bronchiectasis.

• It also demonstrates the degree of fibrosis.

• Findings may be used to follow disease progression.

Other Tests:

• Pulmonary function testing

• This usually demonstrates restriction with a reduced or normal diffusion capacity.

• Obstructive airway disease has been reported occasionally.

• Arterial blood gas measurement: This may be helpful in assessing the severity of illness, but the findings are nonspecific. Findings include the following:

• Partial pressure of oxygen (PO₂) measurement is normal.

• Profound hypoxemia and/or an increased alveolar to arterial (A-a) oxygen gradient is present.

• Pulse oximetry is used for screening, but it may not detect an A-a gradient. It should be checked at rest and following exercise.

Procedures:

• Bronchoscopy with transbronchial biopsy

• Generally, this is diagnostic if multiple biopsies are obtained from several affected subsegments.

• Exact sensitivity and specificity of transbronchial biopsy is not reported.

• Open lung biopsy is the criterion standard. It may be required in the face of nonspecific or equivocal findings, as with extensive fibrosis.

TREATMENT

Medical Care:

• Asymptomatic and physiologically unaffected patients may not require treatment.

• Symptomatic patients may require supportive care and immunosuppressives, chiefly corticosteroids. No controlled treatment trials have been reported. Consider oxygen supplementation based on blood gas and/or exercise oximetry findings.

• Antibiotics are used for associated pulmonary infections.

• In pediatric patients with HIV, empiric treatment for LIP often is initiated based on the findings of subacute dyspnea, mild hypoxemia, and clubbing.

• LIP has been reported to improve with the use of zidovudine alone. Whether highly active antiretroviral therapy (HAART) helps treat LIP is unclear at this time, but paradoxical worsening on HAART therapy may occur.

• Bronchodilators may be used for associated wheezing.

Consultations:

• Consultation with a pulmonologist or thoracic surgeon may be necessary to obtain transbronchial biopsy or open lung biopsy, respectively.

• In cases associated with HIV infection, consultation with a specialist familiar with HIV care is recommended.

Activity:

• Activity may be limited by exercise-induced oxygen desaturation.

• Perform exercise oximetry to determine if supplementary oxygen is needed.

MEDICATION

Medications should be used in patients who are symptomatic or physiologically compromised. Carefully weigh risks and benefits of immunosuppressive therapy in these patients.

Use of antiretroviral agents has been proposed, but whether treatment with these agents ameliorates LIP remains unclear. The potential exists for paradoxical worsening of LIP while on HAART.

Drug Category: Corticosteroids -- Used when patient is symptomatic and/or has physiologic compromise due to LIP. Risks of infection, osteoporosis, hyperglycemia, weight gain, dermatologic changes, and other potential toxicities should be weighed against any potential benefit.

Drug Name	Prednisone (Deltasone) -- For use as immunosuppressant in autoimmune disorders. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation. Doses on lower end of range are prescribed for at least 1 mo and tapered as tolerated. More than 50% respond. In some instances, chronic low-dose suppressive therapy required.
Adult Dose	0.5-1 mg/kg/d PO
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity, viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, fungal or tubercular skin infections, GI disease
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Category: Alkylating agents -- Are used when disease is refractory to corticosteroid therapy. Should be considered only in cases clearly unresponsive to corticosteroids used in high dosage. Should only be prescribed by physicians familiar with usage and toxicities. Generally prescribed for several weeks at a time; disease manifestations and complete blood count should be monitored.

Drug Name	Chlorambucil (Leukeran) -- Reportedly given in pre-HIV era to patients with LIP refractory to corticosteroids. Anecdotal results, efficacy unclear.
Adult Dose	0.1 mg/kg/d PO
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; previous resistance to medication
Interactions	None reported
Pregnancy	D - Unsafe in pregnancy
Precautions	Causes infertility, is carcinogenic, and causes myelosuppression; lowest possible doses should be used; monitor CBC for neutropenia, lymphopenia, anemia, and thrombocytopenia; dosage is decreased or discontinued if counts fall below normal values; if rash develops, discontinue drug because it may cause severe Stevens-Johnson syndrome; potentially epileptogenic medication and should be administered with care to patients with history of seizure disorder, head trauma, or who receive other epileptogenic agents; monitor for GI bleeding or symptoms

FOLLOW-UP

Further Inpatient Care:

• Exclude pulmonary infections.

• The presence of adequate oxygenation should be ascertained. Arrange for ambulatory supplementary oxygen if necessary.

• If a transbronchial or open lung biopsy has been performed, postprocedure pneumothorax should be excluded or demonstrated to be small and stable by expiratory chest radiographs.

Further Outpatient Care:

• Periodically perform pulse oximetry at rest and with exercise.

• Encourage consistent use of a standardized exercise course such as a long corridor or several flights of steps.

• Obtain periodic chest radiographs and/or chest CT scan.

• Assesses for improvement on therapy

• Helps detect exacerbation of LIP or other pulmonary pathology, notably infections

• Assesses for residual fibrosis

• Determining if remaining respiratory compromise is related to pulmonary fibrosis or some other pulmonary pathology is critical.

• Obtain clinical reevaluation, radiography, and/or chest CT scan if patient continues to require high-dose steroids.

• A change in sputum may be the only sign of infection.

In/Out Patient Meds:

• After the first month of therapy and if disease activity allows it, gradually taper prednisone dosage. Use the lowest possible dose to suppress this chronic interstitial pneumonitis.

• Monitor patient for signs of infection and other toxicities of corticosteroid or immunosuppressive therapy.

Transfer:

• Adequate gas exchange and a stable airway are required.

• Appropriate medical records and copies of actual chest radiographs should be transferred.

Complications:

• Bronchiectasis has been associated with LIP. Whether this is due to LIP or the frequent bacterial infections these patients experience remains unclear.

• Bronchitis and pneumonia commonly occur in these patients, with or without bronchiectasis.

• Pulmonary fibrosis may be a long-term complication. Generally, it is indolent.

• Respiratory failure has been reported, especially in the pediatric population.

• Malignant transformation to lymphoma or association with lymphoid malignancy has been reported.

Prognosis:

• Clinical course is variable. The duration is 1 month to 11 years. It often is stable for months without treatment, and sometimes it improves spontaneously.

• Symptoms often are recurrent and occasionally may lead to end-stage fibrosis or bronchiectasis.

• Mortality data are inexact due to lack of reported follow-up and the anecdotal nature of reports.

Patient Education:

• Instructions to patients should include relating all potential toxicities of corticosteroids, including aseptic necrosis of the femoral head, infections, weight gain, hyperglycemia, and other adverse effects.

• Instruct patients to seek medical attention for increased dyspnea or change in sputum.

PICTURES

Caption: Picture 1. Chest radiograph of lymphocytic interstitial pneumonia in an adult who is HIV positive and has exertional dyspnea, demonstrating characteristic fine bibasilar interstitial markings
Picture Type: X-RAY