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Lymphocytic Interstitial Pneumonia

LIP

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. It is characterized by inflammatory alveolar infiltration leading to clinical manifestations. Imaging studies and lung biopsy are necessary to confirm the diagnosis.


Presentation

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.

Cough
  • LIP is often mistaken for pulmonary TB (miliary) because of the chronic cough and the miliary-like pattern on chest X-ray.[books.mcai.org.uk]
  • […] may progress to lymphoma. lymphocytic interstitial pneumonia A diffuse pulmonary disease of insidious onset that is most common in middle-aged , which may be accompanied by Sjögren's disease, hyper- or hypo-gammaglobulinemia Clinical Progressive SOB, cough[medical-dictionary.thefreedictionary.com]
  • Symptoms include fever, cough, and shortness of breath.[en.wikipedia.org]
  • […] general 1/3 associated with Sjögren's syndrome; also associated with AIDS, pulmonary drug reactions May occur in children with AIDS May be an IgG4 related disease May be EBV related, particularly in non HIV related cases Symptoms : shortness of breath, cough[pathologyoutlines.com]
  • Definition Chronic lung disease characterized by interstitial lymphocytic infiltration Alternate/Historical Names LIP Lymphocytic interstitial pneumonia Diagnostic Criteria Clinical Gradual onset of dyspnea, cough Most have symptoms 6 months May occur[surgpathcriteria.stanford.edu]
Dyspnea
  • The features in children are slightly different and can include clubbing, dyspnea, lymphadenopathy, parotid enlargement, and hepatosplenomegaly.[symptoma.com]
  • Patients should be instructed to seek medical attention for increased dyspnea or change in sputum.[emedicine.medscape.com]
  • Definition Chronic lung disease characterized by interstitial lymphocytic infiltration Alternate/Historical Names LIP Lymphocytic interstitial pneumonia Diagnostic Criteria Clinical Gradual onset of dyspnea, cough Most have symptoms 6 months May occur[surgpathcriteria.stanford.edu]
  • […] correlates well with pathologic honeycombing 5) 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[mdnxs.com]
  • Symptoms and examination findings are also generally non-specific, with cough and dyspnea being the hallmark, as previously reported in the HIV uninfected persons with LIP [ 1 , 3 ].[bmcpulmmed.biomedcentral.com]
Rales
  • 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]
  • During the physical examination, chest auscultation can reveal rales and clubbing.[symptoma.com]
  • […] examination findings in children may include the following: Generalized lymphadenopathy Hepatosplenomegaly Parotid enlargement Clubbing Wheezing (occasional) Physical examination findings in adults may include the following: Generalized lymphadenopathy Rales[emedicine.medscape.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]
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]
  • A dry cough is another symptom. Symptoms often get worse over time. See your doctor if you have trouble breathing. After a diagnosis, you can start treatments to manage the inflammation and scarring.[healthline.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 most common symptoms of interstitial lung disease are a dry cough and shortness of breath .[medicinenet.com]
Pulmonary Disorder
  • 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]
  • 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]
  • Reactive pulmonary disorders. Histopathology 1995;26:405-412. Teirstein AS, Rosen MJ. Lymphocytic interstitial pneumonia. Clin Chest Med 1988;9:467-471. Yousem SA, Colby TV, Carrington CB. Follicular bronchitis/bronchiolitis.[path.upmc.edu]
  • Immunosuppressive and cytotoxic pharmacology for pulmonary disorders. Am J Respir Crit Care Med 1997 ; 155 : 395 –420. 26. Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM.[erj.ersjournals.com]
Vietnamese
  • We describe a case of pSS in a 14-year-old Vietnamese-Canadian girl who presented with pulmonary symptoms, radiologic changes, and biopsy confirmation of lymphocytic interstitial pneumonia.[jrheum.org]
Cyanosis
  • ) 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]
  • 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]
  • 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]
  • His general physical examination was normal, with pulse rate of 88/minute, blood pressure 110/68 mmHg, respiratory rate 22/minute, J.V.P. not raised, cyanosis, lymphadenopathy, clubbing, were not present.[lungindia.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]
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]
Insomnia
  • Insomnia is more common—in fact worse—for people with chronic conditions. Read about it on the blog . Interacting with other PatientsLikeMe members improves your health. Read it on healthaffairs.org .[patientslikeme.com]

Workup

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
  • Overview Lymphocytic interstitial pneumonia (LIP) is a syndrome of fever, cough, and dyspnea, with bibasilar pulmonary infiltrates consisting of dense interstitial accumulations of lymphocytes and plasma cells.[emedicine.medscape.com]
  • Abstract Lymphocytic interstitial pneumonitis (LIP) is characterized by diffuse bilateral pulmonary infiltrations in both lower lobes.[kjim.org]
  • We report the case of a 28-year-old patient with frequent respiratory infections and nodular pulmonary infiltrates, who was diagnosed with common variable immunodeficiency and follicular bronchiolitis.[archbronconeumol.org]
  • Walter Finkbeiner, University of California, San Francisco) History A 16-year-old boy with a history of Crohn’s disease presented with bilateral nodular pulmonary infiltrates. An open-lung biopsy was performed.[nature.com]
  • infiltrate and eosinophilia Hydrochlorothiazide Oxygen Radiation l -Tryptophan CCNU, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea.[clevelandclinicmeded.com]
Reticulonodular Pattern
  • […] with decreased DLCO FOB: BAL lymphocytosis ( 35%) may be seen (also seen in Sarcoid, Berylliosis, HP, drug-induced ILD, lymphoma) -Increased plasma cells and macrophages OLB: required for diagnosis in almost all cases CXR/Chest CT patterns: 1) ILD: reticulonodular[mdnxs.com]
Chlamydia
  • […] hyperplasia) component of follicular bronchiolitis often present diffuse pulmonary cysts ( 16915074 ) Associations pulmonary infections Pneumocystis jiroveci pneumonia Epstein-Barr virus infection HIV infection Legionella pneumonia tuberculosis Mycoplasma Chlamydia[humpath.com]
Decreased Lung Compliance
  • Work of breathing is markedly increased because of decreased lung compliance. Together, these physiologic impairments lead to the exercise intolerance seen in all of the ILDs.[clevelandclinicmeded.com]

Treatment

  • However, responses to different treatments are widely varied, and no single first line treatment represents the default treatment for lymphocytic interstitial pneumonia. [5] References [ edit ] The Pathology of Idiopathic Interstitial Pneumonias Carol[en.wikipedia.org]
  • 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]
  • 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]
  • In the population who does not have HIV infection, half the patients improve with treatment but relapse is common. End-stage fibrosis may follow despite treatment. In the past, high mortality was reported in older patients.[emedicine.medscape.com]
  • May occur in children with AIDS May be an IgG4 related disease May be EBV related, particularly in non HIV related cases Symptoms : shortness of breath, cough and polyclonal gammopathy Often progressive, long standing cases may culminate in lymphoma Treatment[pathologyoutlines.com]

Prognosis

  • 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]
  • Prognosis and Treatment Approximately 33% to 50% of patients with LIP die within 3 to 5 years. However, prognosis depends somewhat on the associated underlying disease condition. In some patients the disease stabilizes or resolves.[humpath.com]
  • Vrations in histilogical patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis. Histopathology 2004;44:585-96. 8. Lee HK, Kim DS, Yoo B, Seo JB, Rho JY, Colby TV, et al .[lungindia.com]
  • 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]
  • Lymphoid interstitial pneumonia: Animations More Lymphoid interstitial pneumonia animations & videos Prognosis for Lymphoid interstitial pneumonia Prognosis for Lymphoid interstitial pneumonia: The prognosis is highly variable with some patients recovering[rightdiagnosis.com]

Etiology

  • . * Comprehensive current coverage of basic models of etiology and pathogenesis * Complete catalog of autoantibodies produced * Includes an outstanding review of imaging techniques for the diagnosis of lupus and its complications for each organ system[books.google.com]
  • 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]
  • 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.[symptoma.com]
  • 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]
  • 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.medscape.com]

Epidemiology

  • 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]
  • 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.medscape.com]
  • […] bronchiolitis RBILD DIP Pulmonary Langerhans’ cell histiocytosis (pulmonary histiocytosis X)—most patients are smokers, and some have remission of the disease after cessation of smoking Usual interstitial pneumonia/idiopathic pulmonary fibrosis (smoking is an epidemiologically[nature.com]
Sex distribution
Age distribution

Pathophysiology

  • 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.medscape.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]
  • Pathophysiology As the name implies, the histologic abnormalities that characterize ILD generally involve the pulmonary interstitium to a greater extent than the alveolar spaces or airways, although exceptions exist.[clevelandclinicmeded.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]

Prevention

  • 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.medscape.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]
  • Steroids can be used to prevent or to treat infusion-related RTX symptoms, but this should be used only prior to or immediately after the RTX infusion, and should not be continued beyond 3 days. The use of systemic steroids should be recorded.[clinicaltrials.gov]

References

Article

  1. Kim J-Y, Park S-H, Kim S-K, et al. Lymphocytic interstitial pneumonia in primary Sjogren's syndrome: a case report. Korean J Intern Med. 2011 Mar; 26 (1): 108 -111
  2. Panchabhai TS, Farver C, Highland KB. Lymphocytic interstitial pneumonia. Clin Chest Med. 2016 Sep 3; 37(3): 463-74
  3. Swigris JJ, Berry GJ, Raffin TA, Kuschner WG. Lymphoid interstitial pneumonia: a narrative review. Chest. 2002;122:2150–2164.
  4. Alkhayer M, McCann BG, Harrison BD. Lymphocytic interstitial pneumonitis in association with Sjogren's syndrome. Br J Dis Chest. 1988;82:305–309.
  5. Ferguson EC, Berkowitz EA. Lung CT: Part 2, The interstitial pneumonias-clinical, histologic, and CT manifestations. AJR Am J Roentgenol. 2012;199 (4): W464-76.
  6. Wu W, Zhou J, Di L-G, Chen H. From lymphocytic interstitial pneumonia to MALT lymphoma of lung: a case report with a 5-year diagnostic dilemma. 2015; 8(8): 9698-9702
  7. Couderc LJ, D'Agay MF, Danon F, et al. Sicca complex and infection with human immunodeficiency virus. Arch Intern Med. 1987 May; 147(5):898-901.
  8. Cha S-I, Fessler MB, Cool CD, et al. Lymphoid interstitial pneumonia: clinical features, associations, and prognosis. Eur Respir J. 2006; 28:364-369
  9. Becciolini V, Gudinchet F, Cheseaux JJ, Schnyder P. Lymphocytic interstitial pneumonia in children with AIDS: high-resolution CT findings. Eur Radiol. 2001;11(6):1015-20.
  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.

Symptoms

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