We present a 39-year-old female with HIV, medication non-compliance, and recurrences of bacterial pneumonia. She presented with a two-day bout of worsening shortness of breath, dyspnea and productive cough. A CT of the chest was notable for multi-lobular pneumonia. She underwent flexible bronchoscopy and biopsy which revealed lymphocytic interstitial pneumonitis. Conclusion: Recurrent bacterial pneumonia is a rare complication of lymphoid interstitial pneumonia (LIP) in HIV positive patients, and should be considered in the differential as a possible precipitator of recurrent pneumonia inan HIV positive patient.
There are two idiopathic interstitial pneumonias associated with human immunodeficiency syndrome (HIV): Lymphoid Interstitial Pneumonia (LIP) and Nonspecific Interstitial Pneumonia (NSIP) according to the American Thoracic Society/European Respiratory Society (ATS/ ERS) Consensus Statement published in 2002 [
A 39-year-old African American female presented to the emergency room March 3rd, 2009 with a two dayhistory of worsening dyspnea, productive cough and chest tightness. Her past medical history was significant for AIDS diagnosed in 1994 with CD4 T-cell count of 131, childhood asthma and emphysema. She was not taking antiretroviral therapy or any other regular medications. She admitted to a history of chronic tobacco use (40 pack/ years) but denied intravenous drug abuse. She had three previous hospitalizations for confirmed bacterial pneumonia over the past year with her most recent hospitalization one month prior to this current case presentation.
On physical examination, her temperature was 98.7˚F, heart rate 116 beats/minute, blood pressure 119/57 mmHg and respiratory rate 19 breaths/minute. The patient was using accessory muscles of respiration and had decreased breath sounds with diffuse wheezes bilaterally. She had left lower lobe crackles and the rest of the examination was normal.
Her initial arterial blood gas showed: pH 7.42, pCO2 41 mmHg, HCO3 27, pO2 68 mmHg and saturation of 94% while breathing two liters of oxygen. The calculated alveolar-arterial oxygen difference (P(A-a)O2) was 30 mmHg. The white blood cell count was 23.9 th/cm, hemoglobin 13.1 g/dl and platelet count 171 th/cm. The CD 4 T-cell count was 131 cells/ul, CD 8 T-cell count was 778 cells/ul and CD 4/CD 8 ratio was 0.16. Chest roentgenogram showed hyperaeration with bilateral upper lobe bullae and bibasilar interstitial disease (
She was empirically treated for hospital acquired pneumonia with piperacillin-tazobactam, vancomycin and le-
vaquin. She was initiated on steroids and nebulizers for COPD. The patient demonstrated minimal respiratory improvement over the next 24 hours. A follow up thoracic computer topography (CT) scan without contrast showed a 1 cm irregular border nodular density in the apical posterior segment of the left upper lobe and patchy opacities in the middle lobe, lingular and lower lobes (
Transbronchial biopsy showed evidence of lymphocytic interstitial pneumonitis with diffuse interstitial infiltration, mature lymphocytes, plasma cells, macrophages, neutrophils and moderate benign squamous cells (
Stains and cultures for acid fast bacilli, Pneumocystis jiroveci and fungi were negative. Repeat blood cultures were negative.
The patient clinically improved with peak flows back to baseline and pulse oxygen saturations in the mid to
upper 90’s on room air. The patient was discharged with a steroid taper, and oral levaquin (for 10 days) as she appeared clinically stable. However, the patient was lost toimmediate outpatient follow-up.
This case highlights LIP as a rare condition (affecting only about 3% of HIV positive patients) that has previously been implicated to rarely cause the complication of recurrent bacterial pneumonias [
In patients with HIV not on HAART, who present with inexplicable recurrent bouts of bacterial pneumonia, the astute clinician should consider LIP in the differential underlying diagnosis for increased susceptibility. This in turn will reduce morbidity and mortality for these patients as LIP remains an often overlooked etiology.
LIP, itself, was first described by Liebow and Carrington in 1969 [
have all been described on pathology [
The differential diagnosis of predominantly lymphocytic interstitial infiltrates on lung biopsy specimens of HIV-positive patients ranges from infectious etiologies, for instance, Pneumocystis jiroveci pneumonia, viral pneumonia, EBV-associated infections (infectious mononucleosis or post-transplant lymphoproliferative disorders) to non-infectious lymphoproliferative disorders such as hypersensitivity pneumonitis, sarcoidosis, Langerhans’ cell histiocytosis, malignant lymphomas and drug-induced interstitial pneumonitis, for example, caused by diphenylhydantoin use [1,8].
LIP occurs more commonly in females, particularly in their fifth decade of life, however the disease can occur at any age [1,9]. In HIV-positive children younger than 13 years of age, LIP is an AIDS defining illness [
LIP was first reported to be associated with HIV in case reports published in the 1980’s [
The altered trafficking of lymphocytes in LIP leading to increased epithelial permeability is mediated predominantly by CD 8+ cytotoxic lymphocytes which can destroy HIV-infected macrophages in vitro, leading to release of cytokines [
In addition to HIV, LIP has been associated with other infectious diseases including Epstein Barr Virus (EBV), human T-cell leukemia virus type I and III (HTLV-I and III), legionella, mycoplasma, chlamydia, tuberculosis, and chronic active hepatitis [2,9,13,14]. It has previously been reported that patients dually infected with HIV and EBV have a higher likelihood of developing LIP [2,9]. However, a review article concluded that though some patients with HIV may have EBV antigen and antibody positivity in lung biopsy, it is quite possible that another condition could have contributed to the disease process in their LIP [
LIP is associated with many lymphoproliferative and autoimmune disorders, including Sjogren’s syndrome, rheumatoid arthritis, autoimmune hemolytic anemia, systemic lupus erythematosus, dysproteinemias (agammaglobulinemias, common variable immune deficiency and hypergammaglobulinemias due to elevation of IgM and IgG), myasthenia gravis, autoerythrocyte sensitization syndrome, chronic active hepatitis with renal tubular acidosis, primary biliary cirrhosis, pernicious anemia, celiac sprue, autoimmune thyroid disease, multicentric Castleman’s disease and allogenic bone marrow transplantation [1,2,7,9,15].
Adults with LIP usually present with moderate to severe respiratory symptoms [
Chest imaging studies are imperative in working up the diagnosis of LIP. Chest x-rays have been reported to appear in several forms predominantly affecting the lower lung zones. These are listed as follows: 1) normal; 2) fine reticular nodular infiltrates; 3) larger reticular nodular infiltrates (features may mimic miliary tuberculosis); 4) combination of #1 and #2 with superimposed alveolar opacities; and 5) focal consolidations [2,6]. Of note, LIP may also lead to atelectasis, fibrosis or bronchiectasis that may be detected on chest imaging [
Pulmonary function testing has mainly demonstrated restrictive disease with a reduced or normal total lung diffusion capacity, though obstructive disease and normal findings have also been reported in LIP [6,17]. Arterial blood gas measurements are unhelpful as they may reveal a normal PaO2, or mild to profound hypoxaemia with an increased alveolar to arterial oxygen gradient [
As in our patient’s case, the diagnosis of LIP can be made via transbronchial biopsy, but the gold standard of diagnosis is thoracoscopic or open-lung biopsy [6,9]. This is because transbronchial biopsy has a lower diagnostic yield (small sample size, which often leads to multiple biopsy attempts) and increased risks of complications such as pneumothorax [
Due to LIP’s rarity, no controlled trials have been carried out to offer a standard recommended treatment regimen. However, immuno-suppression with steroids appears to be key in the initiation of therapy based on prior reports [
No studies limited to individual non-nucleoside reverse transcriptase inhibitors have been recorded in the management of LIP, but HAART has been shown to suppress LIP in several reports [6,18,19]. However, one case report showed manifestation of LIP as a complication of immune reconstitution syndrome shortly after the initiation of HAART [
The patient described in this case exhibited recurrent bouts of bacterial pneumonia, as well as clinical, radiographic and pathological features commonly found in lymphoid interstitial pneumonia (LIP). The complication of repeated bouts of bacterial pneumonia is a rare feature of LIP in HIV positive patients with LIP. To our knowledge, this is one of the first reported cases since the widespread availability and use of HAART.