The etiology of lymphocytic interstitial pneumonia (LIP) is unknown. It is characterized by infiltration of the pulmonary alveoli by inflammatory lymphocytes, plasma cells and histiocytes [1]. LIP is often associated with autoimmune conditions like Sjögren's syndrome, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Hashimoto thyroiditis as well as immunodeficient diseases like human immunodeficiency virus infection (HIV), combined variable immunodeficiency, agammaglobulinemia, and Epstein-Barr virus (EBV) infection [2] [3] [4].

Although LIP has been reported in patients of all age groups, a majority of the patients are middle-aged and the incidence is higher amongst females [5]. If LIP occurs in a pediatric patient, then it should raise suspicion of underlying acquired immunodeficiency syndrome (AIDS).

Patients with LIP often do not present any signs of the disease and are diagnosed incidentally based on radiological findings [6]. Symptoms when present can be nonspecific such as a long-standing cough becoming worse with time, dyspnea, chest pain, rarely hemoptysis [6], anorexia, fever, night sweats and joint pain. Clinical manifestations of associated diseases like parotid enlargement, xerophthalmia and xerostomia [7] can also be present. The features in children are slightly different and can include clubbing, dyspnea, lymphadenopathy, parotid enlargement, and hepatosplenomegaly.

As the disease progresses, patients develop bronchitis, bronchiectasis and eventually, pulmonary fibrosis. The incidence of respiratory failure with cyanosis is higher amongst children with LIP.

• Pseudotumor

  The disorders discussed include lymphocytic interstitial pneumonitis, follicular bronchiolitis, nodular lymphoid hyperplasia, inflammatory pseudotumor, Castleman disease, immunoglobulin G4related disease in the lung, and posttransplant lymphoproliferative [mayoclinic.pure.elsevier.com]

  The disorders discussed include lymphocytic interstitial pneumonitis, follicular bronchiolitis, nodular lymphoid hyperplasia, inflammatory pseudotumor, Castleman disease, immunoglobulin G4-related disease in the lung, and posttransplant lymphoproliferative [ncbi.nlm.nih.gov]

• Cough

  Children develop cough and decreased ability to exercise, and they may not grow and gain weight. Adults develop difficulty breathing and cough over months or, in some cases, years. [msdmanuals.com]

  She presented with dyspnea, cough, weight loss, and bibasilar pulmonary infiltrates. Lung biopsy demonstrated lymphocytic interstitial pneumonia and corticosteroid therapy resulted in clinical and radiological improvement. [ncbi.nlm.nih.gov]

• Dyspnea

  The features in children are slightly different and can include clubbing, dyspnea, lymphadenopathy, parotid enlargement, and hepatosplenomegaly. [symptoma.com]

  She presented with dyspnea, cough, weight loss, and bibasilar pulmonary infiltrates. Lung biopsy demonstrated lymphocytic interstitial pneumonia and corticosteroid therapy resulted in clinical and radiological improvement. [ncbi.nlm.nih.gov]

• Dry Cough

  Breathlessness during exercise is one of the initial symptoms of these diseases, while a dry cough may also be present. People with different types of ILD may have the same kind of symptoms but their symptoms may vary in severity. [books.google.com]

  Here we present a case of LIP in an immunocompetent adult male presented with history of persistent dry cough and breathlessness on exertion, confirmed on HRCT chest and histopathologically, treated successfully with steroids. [lungindia.com]

  AIDS); especially in children Monoclonal or polyclonal gammopathy Common variable immunodeficiency Idiopathic LIP accounts for 20% of cases ( Eur Respir J 2006;28:364 ) Clinical features Very slowly progressive respiratory symptoms Dyspnea on exertion Dry [pathologyoutlines.com]

  She remained fit and well until late 2014, when she presented to her primary care physician with a six week history of a dry cough and progressive shortness of breath. She was uncomplaining of other symptoms. [scitechnol.com]

  The symptoms will vary from person to person, but the most common symptoms of an ILD are: Shortness of breath, especially with exertion or exercise Dry cough that does not produce phlegm Labored breathing Although rapid worsening can happen, ILD's symptoms [uchospitals.edu]

• Rales

  During the physical examination, chest auscultation can reveal rales and clubbing. [symptoma.com]

  Pleural effusion: uncommon (suggests presence of complicating lymphoma) Hypo or hypergammaglobulinemia: may be seen Serum autoantibodies or immune complexes: may be positive Clinical Clubbing (common) Dyspnea: Cough: Pleuritic Chest Pain: Bibasilar Rales [mdnxs.com]

  […] loss of volume is characteristic of either UIP or scleroderma Clinically Symptoms include SOB, non-productive cough and fatigue Clubbing of the fingers is very common (85%) Cyanosis and pulmonary hypertension usually occur late in the disease “Velcro” rales [learningradiology.com]

  Bibasilar rales are a consistent finding on lung auscultation (1,3,4,16); wheezes and decreased breath sounds may also be present (4). However, in many instances, the physical findings are minimal (1) or the physical examination is normal (1,12). [path.upmc.edu]

  On physical examination, she had bibasilar crackling rales. Pale conjunctiva, hepatomegaly by two fingers width below the costal margin and pretibial pitting edema were also discovered. But, clubbing of finger and cyanosis were absent. [kjim.org]

• Pulmonary Disorder

  Lymphocytic interstitial pneumonia is a rare, slowly progressive pulmonary disorder associated with autoimmune diseases, dysgammaglobulinemia, human immunodeficiency virus infection and Epstein-Barr virus infection or it could be idiopathic. [symptoma.com]

  < Previous | Contents | Next > Lymphocytic interstitial pneumonitis (LIP) LIP is a non-infectious pulmonary disorder caused by white cell infiltration into alveolae. [books.mcai.org.uk]

  Pulmonary lymphoproliferative disorders and related conditions. In: Spencer's Pathology of the Lung, fifth edition, 1996, Hasleton PS, ed., New York, McGraw-Hill, pp. 1111-1129. Hasleton PS. Hypersensitivity pneumonitis. [path.upmc.edu]

  Pulmonary lymphoid disorders. Semin Diagn Pathol 1995 ; 12 : 158 –171. 4. ↵ Katzenstein ALA, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. [erj.ersjournals.com]

• Cyanosis

  The incidence of respiratory failure with cyanosis is higher amongst children with LIP. The diagnosis of LIP is often delayed due to the nonspecific symptoms. A clinical suspicion is required to detect the condition. [symptoma.com]

  Dyspnea: Cough: Pleuritic Chest Pain: Bibasilar Rales: Pulmonary HTN: late Other System Involvement: a) Lymphadenopathy: b) Keratoconjunctivitis sicca: c) Salivary Gland Enlargement: d) Hepatosplenomegaly: e) Fever: f) Weight Loss: g) Clubbing: h) Cyanosis [mdnxs.com]

  If the disease progresses to the end-stage respiratory failure cyanosis and clubbing may develop. Hypertrophy of the salivary glands observed in 20% of patients 11. [radiopaedia.org]

  Becomes coarser as disease progresses and ends with honeycomb lung Progressive loss of volume is characteristic of either UIP or scleroderma Clinically Symptoms include SOB, non-productive cough and fatigue Clubbing of the fingers is very common (85%) Cyanosis [learningradiology.com]

  But, clubbing of finger and cyanosis were absent. A chest radiograph showed pneumonic infiltrations in both lower lung fields with pleural effusion ( Figure 1B ). [kjim.org]

• Parotid Swelling

  The child is often asymptomatic in the early stages, but may later have a mild persistent cough, with or without difficulty in breathing, bilateral parotid swelling, persistent generalised lymphadenopathy, poor growth, hepatomegaly and other signs of [books.mcai.org.uk]

The diagnosis of LIP is often delayed due to the nonspecific symptoms. A clinical suspicion is required to detect the condition. Patients may provide a history of progressively worsening symptoms. During the physical examination, chest auscultation can reveal rales and clubbing.

Routine laboratory tests will show elevated levels of inflammatory markers in the presence of autoimmune disease and polyclonal agammaglobulinemia or dysgammaglobulinemia on serum protein electrophoresis. Tests for HIV, EBV, RA factor, SLE, Sjögren's and Hashimoto thyroiditis should be performed to detect the disorders associated with LIP. Lactate dehydrogenase (LDH) levels are obtained in pediatric patients to differentiate LIP from pneumocystis carinii pneumonia.

Restrictive pattern and diminished diffusion capacity are seen on pulmonary function testing [8].

Plain X-ray chest may show bilateral basal opacities and cysts. Computed tomography (CT) scan is obtained to determine the extent of lung involvement and for subsequent follow-up of the disease. Findings include cysts, opacified nodules, bronchiectasis, bullae with air bronchogram and pulmonary fibrosis in the late stages of LIP [9] [10].

Bronchoalveolar lavage is performed to exclude infection and is likely to reveal lymphocytic infiltrate [8].

However, confirmation of diagnosis requires histological examination of a lung biopsy specimen [6]. The typical features of LIP are widening of the alveolar septae with extensive interstitial lymphocytic, plasma cell and histiocytic infiltration. Immunohistochemical staining and flow cytometry are required to differentiate between LIP and pulmonary lymphoma. Polyclonal infiltrate (i.e. both T and B cells) is seen in LIP, while monoclonal infiltrate with destruction/distortion of the airways and vessels and pleural involvement are a feature of lymphomas [2].

• Pulmonary Infiltrate

  After a diagnostic surgical lung biopsy, his hypoxemia and pulmonary infiltrates exacerbated rapidly over a few days, although his condition had not progressed during the previous year. [ncbi.nlm.nih.gov]

  It is characterized radiologically by bilateral lower lobe infiltrates, and histologically by a polymorphic lymphoplasma cell infiltration of the pulmonary interstitium. [kjim.org]

• Reticulonodular Pattern

  Eight children of 12 had a reticulonodular pattern on chest radiographs. Two children had normal chest films and two children showed peribronchiolar thickening. [ncbi.nlm.nih.gov]

  OLB: required for diagnosis in almost all cases CXR/Chest CT patterns: 1) ILD: reticulonodular pattern (most common) 2) Mixed alveolar-interstitial infiltrates: due to coalescence 3) Hilar/ mediastinal nodes: in some cases 4) Honeycombing: small cysts [mdnxs.com]

• Anterior Mediastinal Mass

  (s), segmental or lobar in size mimicking pneumonia Over time gradually grow toward periphery of lung May also arise in lung periphery Unilateral or bilateral Pleural effusions rare Associated findings Anterior mediastinal mass: Thymoma Predisposing condition [radiologykey.com]

However, responses to different treatments are widely varied, and no single first line treatment represents the default treatment for lymphocytic interstitial pneumonia. [en.wikipedia.org]

Because of severe general condition of the patient, immunosuppressive treatment was started immediately, without further invasive diagnostics including lung biopsy, which is required for a definitive diagnosis. [journals.viamedica.pl]

(IgG normal range: 6–16 g/l; IgM normal range: 0.4–2.4 g/l; IgA normal range: 0.8–4.0 g/l). ( E ) ESR during course of treatment (normal range: 1–12 mm/h). ( F ) CRP during course of treatment (normal range: D – F ) Boxes relate to treatment periods [academic.oup.com]

However, responses to different treatments are widely varied, and no single first line treatment represents the default treatment for lymphocytic interstitial pneumonia. [5] References ↑ The Pathology of Idiopathic Interstitial Pneumonias Carol Farver [ipfs.io]

2016;21:600 ) Corticosteroid therapy is commonly used as a first line treatment and improves the symptoms in most cases Immunosuppression (eg, cyclophosphamide, azathioprine, cyclosporine A) may be used as a second line Treatment for underlying disease [pathologyoutlines.com]

Pulmonary malignat lymphomas: Classification, theraphy and prognosis. Cancer, 16 (1963), pp. 928-955 [2.] C.B. Carrington, A.A. Liebow. Lymphocytic interstitial pneumonia (abtr.). Amer J Path, 48 (1966), pp. 36 [3.] A.A. Liebow. [archbronconeumol.org]

Although the clinical presentation may be identical to the more common opportunistic infections, the treatment differs, and the prognosis may be better. [ncbi.nlm.nih.gov]

Treatment and prognosis With smoking cessation and corticosteroid therapy, the prognosis is good. The overall prognosis of has been described as being significantly better than that of fibrotic NSIP 11. [radiopaedia.org]

Table 6— Prognosis and cause of death DISCUSSION In the present study, the authors sought to define the clinical features, associations and prognosis of biopsy-proven histopathological LIP. [erj.ersjournals.com]

Low-Grade Pulmonary or Systemic Lymphoma: may occur in some cases 2) Infection (especially in cases with associated dysproteinemia): Treatment Steroids: may markedly improve disease (cited in few case reports) Some cases progress to death despite therapy Prognosis [mdnxs.com]

Epstein-Barr virus and Chlamydia trachomatis are potential etiologic agents, but a specific cause remains to be identified. This disorder has been described with a higher frequency in pediatric AIDS. [ncbi.nlm.nih.gov]

Evidence of an autoimmune etiology includes its frequent association with Sjögren syndrome (25% of cases of LIP) and other disorders (eg, SLE, RA, Hashimoto thyroiditis —14% of cases). [msdmanuals.com]

Evidence of an autoimmune etiology includes its frequent association with Sjögren syndrome (25% of cases of LIP) and other disorders (eg, systemic lupus erythematosus, rheumatoid arthritis, Hashimoto thyroiditis—14% of cases). [merckmanuals.com]

The etiology of LIP remains unclear. The vast spectrum of disorders associated with this condition further complicates investigation. In 1973, Liebow and Carrington suggested multiple possible etiologies, including a viral agent (1). [path.upmc.edu]

Epidemiology Sex: more common in females than males Age: usually presents in 30’s-50’s (may be seen in children, particularly those with hypogammaglobulin-emia or AIDS) Etiology Dysproteinemia Hypogammaglobulinemia Monoclonal or Polyclonal Gammopathy [mdnxs.com]

Oral Oncol 34:284–291. 7- Ho T, Wei Q, Sturgis EM (2007) Epidemiology of carcinogen metabolism genes and risk of squamous cell carcinoma of the head and neck. [otorrinocontiplanes.com]

Summary Epidemiology The incidence of HP is unknown. A population-based study estimated the annual incidence of interstitial lung diseases as 1/3300 and HP accounted for less than 2% of these cases. [orpha.net]

[…] immunodeficiency virus (HIV) infection On histology, diffuse infiltration of polyclonal lymphocytes with scant interstitial fibrosis is characteristic Terminology Also called lymphocytic interstitial pneumonia ICD coding J84.2 : lymphoid interstitial pneumonia Epidemiology [pathologyoutlines.com]

Epidemiology Lymphocytic interstitial pneumonia (LIP) is an uncommon disease. In the United States, however, it is found in 22-75% of pediatric patients with HIV who have pulmonary disease. [emedicine.com]

[…] coding J84.2 : lymphoid interstitial pneumonia Epidemiology Rare Typical onset at ages 40 - 70 years old but can occur at any age ( Chest 2002;122:2150 ) More common in women No association with smoking history Sites Bilateral lower lobes of the lung Pathophysiology [pathologyoutlines.com]

Liebow AA, Carrington CB: The interstitial pneumonias, in Simon M, Potchen EJ, Le May M (eds): Frontiers of Pulmonary Radiology: Pathophysiologic, Roentgenographies and Radioisotopic Considerations. New York, Grune & Stratton, 1969, pp 102–141. [link.springer.com]

For other discussions on pneumonia, see the following: Pathophysiology and Etiology HIV-related lymphocytic interstitial pneumonia (LIP) may be part of a continuum of lymphocytic infiltrative disorders, such as pulmonary lymphoid hyperplasia in children [emedicine.com]

Immunodiagnostic and pathophysiologic aspects of antineutrophil cytoplasmic antibodies in vasculitis. Curr Opin Rheumatol 1995; 7 : 11–19. 71 Edgar JD, McMillan SA, Bruce IN, Conlan SK. An audit of ANCA in routine clinical practice. [nature.com]

Ziegler JL, Abram DI: The AIDS related complex, in DeVita VT Jr, Hellman S, Rosenberg SA (eds): AIDS: Etiology, Diagnosis, Treatment, and Prevention. New York, JB Lippincott, 1985, pp 223–234. Google Scholar 22. [link.springer.com]

Can interstitial lung disease be prevented? Interstitial lung disease can be prevented only to the extent that its individual causes may be prevented. [medicinenet.com]

Antifibrotic drugs such as pirfenidone (Esbriet) and nintedanib (Ovef) may prevent further scarring in the lungs. These drugs are both approved by the U.S. Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis. [healthline.com]

In children with HIV infection, lymphocytic interstitial pneumonia has been designated an AIDS-defining illness by the US Centers for Disease Control and Prevention. LIP is more common in women when not associated with HIV infection. [emedicine.com]

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10. Johkoh T, Ichikado K, Akira M, et al. Lymphocytic interstitial pneumonia: follow-up CT findings in 14 patients. J Thorac Imaging. 2000. Jul; 15(3):162-7.