aDepartment of Sexual Health and HIV, UK
bDepartment of Clinical Immunology, King's College Hospital, UK
cDepartment of HIV/GU Medicine, Kings College London, London, UK.
Correspondence to Dr Elizabeth Hamlyn, Caldecot Centre, Kings College Hospital, Denmark Hill, London, SE5 9RS, UK. Tel: +44 7870665620; fax: +44 20 32993486; e-mail: email@example.com
Lymphocytic interstitial pneumonitis (LIP) may affect up to one-third of HIV-infected children  but is a rare complication in adults. The condition is characterized by an accumulation of mononuclear cells in the pulmonary interstitium, although the exact cause and pathogenesis are unknown. High concentrations of HIV RNA may be demonstrated in LIP lesions suggesting that HIV antigens induce local immune activation, including proinflammatory T helper cell type 1 (Th1) cytokine production, resulting in focal accumulation of mononuclear cells and induction of lymphoproliferative responses . We report an adult patient with LIP whose condition improved dramatically following the onset of pregnancy.
A 32-year-old Ghanaian woman presented with 20 kg weight loss, nonproductive cough, fever and breathlessness. Chest radiograph demonstrated bilateral diffuse opacification (Fig. 1a). Bronchioalveolar lavage was negative for Pneumocystis jirovecii, fungi, mycobacteria and malignant cells. HIV-1 antibody test was positive; CD4 T cell count was 108 cells/μl (17%) and HIV RNA level was 22 400 copies/ml. The patient failed to respond to broad spectrum antibiotics and empirical antituberculosis chemotherapy.
After 3 months, her chest radiograph remained unchanged and a computed tomography (CT) scan confirmed the presence of diffuse bilateral consolidation. Thoracoscopic lung biopsy samples were obtained which revealed a diffuse interstitial and peribrochiolar infiltration of T and B cells consistent with a diagnosis of LIP and antituberculous therapy was discontinued. She failed to attend for follow-up and did not receive treatment for LIP.
When the patient was next reviewed 3 months later, she had gained 5 kg weight and her cough had resolved. She reported several weeks of amenorrhoea. A pregnancy test was positive and an ultrasound scan confirmed an intrauterine pregnancy of 11 weeks gestation. A chest radiograph was performed, with appropriate radioprotective precautions, and showed almost complete resolution of the bilateral consolidation (Fig. 1b). She commenced antiretroviral therapy (ART) consisting of abacavir, lamivudine and nevirapine and, at the time of delivery, her CD4+ T cell count had risen to 222 /μl (21%) and her viral load was undetectable. She had a normal vaginal delivery at 38 weeks gestation to a healthy, HIV-uninfected infant. Six months after delivery, she had regained her premorbid weight of 65 kg, remained on ART, and her LIP had not recurred.
An interesting fact was that the onset of pregnancy was associated with a clinical and radiological improvement of LIP in our patient. Pregnancy results in changes in the maternal immune status, in particular the suppression of proinflammatory host responses allowing embryonic implantation and preventing foetal rejection. This is characterized by a shift leading to suppressed production of proinflammatory Th1 cytokines and enhanced production of inhibitory Th2 cytokines. Other Th1-mediated conditions, such as rheumatoid arthritis and multiple sclerosis, may undergo remission during pregnancy and relapse during the postpartum period . Th2 responses support pregnancy  and counteract the Th1 response, which has been associated with adverse pregnancy outcome. CD4+CD25+ regulatory T cells are known to increase in human peripheral blood during pregnancy  and may be responsible for dampening antifoetal immune responses. In addition, immune-inhibitory cytokines such as interleukin-10 are elevated in the maternal circulation during pregnancy . It is possible that these mechanisms abrogated the accumulation and proliferation of mononuclear cells in the pulmonary interstitium in our patient with LIP. Although spontaneous resolution cannot be excluded, the dramatic improvement in her condition and the temporal relationship with the onset of pregnancy point to an association. Although our patient commenced ART during her pregnancy, this treatment was only introduced once her LIP had improved. It is possible, however, that ART was instrumental in preventing a clinical relapse of LIP following delivery.
The authors wish to thank Dr Jan Welch who was responsible for the patient's antenatal care.
There are no conflicts of interest.
1. Sharland M, Gibb DM, Holland F. Respiratory morbidity from lymphocytic interstitial pneumonitis (LIP) in vertically acquired HIV infection. Arch Dis Child 1997; 76:334–336.
2. Travis WD, Fox CH, Devaney KO, Weiss LM, O'Leary TJ, Ognibene FP, et al
. Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis. Hum Pathol 1992; 23:529–541.
3. Singh N, Perfect JR. Immune reconstitution syndrome and exacerbation of infections after pregnancy. Clin Infect Dis 2007; 45:1192–1199.
4. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal–fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 1993; 14:353–356.
5. Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S. Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 2004; 10:347–353.
6. Bosio PM, Wheeler T, Anthony F, Conroy R, O'Herlihy C, McKenna P. Maternal plasma vascular endothelial growth factor concentrations in normal and hypertensive pregnancies and their relationship to peripheral vascular resistance. Am J Obstet Gynecol 2001; 184:146–152.