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Abnormal pulmonary interstitial morphology

MedGen UID:
1788738
Concept ID:
C5441745
Anatomical Abnormality
Synonyms: Interstitial lung disease; Interstitial pulmonary abnormality
 
HPO: HP:0006530
Monarch Initiative: MONDO:0015925
Orphanet: ORPHA182095

Definition

Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAbnormal pulmonary interstitial morphology

Conditions with this feature

Niemann-Pick disease, type B
MedGen UID:
78651
Concept ID:
C0268243
Disease or Syndrome
The phenotype of acid sphingomyelinase deficiency (ASMD) occurs along a continuum. Individuals with the severe early-onset form, infantile neurovisceral ASMD, were historically diagnosed with Niemann-Pick disease type A (NPD-A). The later-onset, chronic visceral form of ASMD is also referred to as Niemann-Pick disease type B (NPD-B). A phenotype with intermediate severity is also known as chronic neurovisceral ASMD (NPD-A/B). The most common presenting symptom in NPD-A is hepatosplenomegaly, usually detectable by age three months; over time the liver and spleen become massive in size. Psychomotor development progresses no further than the 12-month level, after which neurologic deterioration is relentless. Failure to thrive typically becomes evident by the second year of life. A classic cherry-red spot of the macula of the retina, which may not be present in the first few months, is eventually present in all affected children. Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. Most children succumb before the third year of life. NPD-B generally presents later than NPD-A, and the manifestations are less severe. NPD-B is characterized by progressive hepatosplenomegaly, gradual deterioration in liver and pulmonary function, osteopenia, and atherogenic lipid profile. No central nervous system (CNS) manifestations occur. Individuals with NPD-A/B have symptoms that are intermediate between NPD-A and NPD-B. The presentation in individuals with NPD-A/B varies greatly, although all are characterized by the presence of some CNS manifestations. Survival to adulthood can occur in individuals with NPD-B and NPD-A/B.
Gaucher disease type I
MedGen UID:
409531
Concept ID:
C1961835
Disease or Syndrome
Gaucher disease (GD) encompasses a continuum of clinical findings from a perinatal lethal disorder to an asymptomatic type. The identification of three major clinical types (1, 2, and 3) and two other subtypes (perinatal-lethal and cardiovascular) is useful in determining prognosis and management. GD type 1 is characterized by the presence of clinical or radiographic evidence of bone disease (osteopenia, focal lytic or sclerotic lesions, and osteonecrosis), hepatosplenomegaly, anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3 are characterized by the presence of primary neurologic disease; in the past, they were distinguished by age of onset and rate of disease progression, but these distinctions are not absolute. Disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years is classified as GD type 2. Individuals with GD type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity.
Sarcoidosis, susceptibility to, 2
MedGen UID:
436694
Concept ID:
C2676468
Finding
Any sarcoidosis in which the cause of the disease is a mutation in the BTNL2 gene.
Sarcoidosis, susceptibility to, 1
MedGen UID:
394568
Concept ID:
C2697310
Finding
Any sarcoidosis in which the cause of the disease is a mutation in the HLA-DRB1 gene.
Familial hemophagocytic lymphohistiocytosis 5
MedGen UID:
416514
Concept ID:
C2751293
Disease or Syndrome
Familial hemophagocytic lymphohistiocytosis-5 with or without microvillus inclusion disease (FHL5) is an autosomal recessive hyperinflammatory disorder characterized clinically by fever, hepatosplenomegaly, pancytopenia, coagulation abnormalities, and other laboratory findings. Some patients have neurologic symptoms due to inflammatory CNS disease. There is uncontrolled and ineffective proliferation and activation of T lymphocytes, NK cells, and macrophages that infiltrate multiple organs, including liver, spleen, lymph nodes, and the CNS. The phenotype is variable: some patients may present in early infancy with severe diarrhea, prior to the onset of typical FHL features, whereas others present later in childhood and have a more protracted course without diarrhea. The early-onset diarrhea is due to enteropathy reminiscent of microvillus inclusion disease (see MVID, 251850). The enteropathy, which often necessitates parenteral feeding, may be the most life-threatening issue even after hematopoietic stem cell transplantation (HSCT). More variable features include sensorineural hearing loss and hypogammaglobulinemia. Treatment with immunosuppressive drugs and chemotherapy can ameliorate signs and symptoms of FHL in some patients, but the only curative therapy for FHL is HSCT. HSCT is not curative for enteropathy associated with the disorder, despite hematologic and immunologic reconstitution (summary by Meeths et al., 2010; Pagel et al., 2012; Stepensky et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL, HLH), see 267700.
Dyskeratosis congenita, autosomal dominant 3
MedGen UID:
462795
Concept ID:
C3151445
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency
MedGen UID:
895551
Concept ID:
C4225400
Disease or Syndrome
Interstitial lung and liver disease is an autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood. Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis (summary by Hadchouel et al., 2015).
Hermansky-Pudlak syndrome 10
MedGen UID:
934713
Concept ID:
C4310746
Disease or Syndrome
Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. Ocular findings include reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects occur primarily in individuals with pathogenic variants in AP3B1 and AP3D1.
Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome
MedGen UID:
1388385
Concept ID:
C4518785
Disease or Syndrome
Junctional epidermolysis bullosa-7 with interstitial lung disease and nephrotic syndrome (JEB7), also known as ILNEB, is an autosomal recessive multiorgan disorder that includes congenital interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa. The respiratory and renal features predominate, and lung involvement accounts for the lethal course of the disease (summary by Has et al., 2012).
Autoimmune interstitial lung disease-arthritis syndrome
MedGen UID:
1800821
Concept ID:
C5243948
Disease or Syndrome
Autoimmune interstitial lung, joint, and kidney disease is an autosomal dominant systemic autoimmune disorder characterized by interstitial lung disease, inflammatory arthritis, and immune complex-mediated renal disease. Laboratory studies show high-titer autoantibodies. Symptoms appear in the first 2 decades of life, but there is incomplete penetrance (summary by Watkin et al., 2015).
Rajab interstitial lung disease with brain calcifications 1
MedGen UID:
1750003
Concept ID:
C5436276
Disease or Syndrome
Rajab interstitial lung disease with brain calcifications-1 (RILCBC1) is an autosomal recessive multisystem disorder with a highly variable phenotype. Most patients present in infancy or early childhood with poor growth and interstitial lung disease, which may lead to death. Some may also have liver, skeletal, and renal abnormalities, and most have intracranial calcifications on brain imaging. Some may have early impaired motor development, but most have normal cognitive development (summary by Xu et al., 2018). Genetic Heterogeneity of Rajab Interstitial Lung Disease with Brain Calcifications Also see Rajab interstitial disease with brain calcifications-2 (RILDBC2; 619013), caused by mutation in the FARSA gene (602918).
Rajab interstitial lung disease with brain calcifications 2
MedGen UID:
1770895
Concept ID:
C5436603
Disease or Syndrome
Rajab interstitial lung disease with brain calcifications-2 (RILDBC2) is an autosomal recessive disorder characterized by growth delay, interstitial lung disease, liver disease, and abnormal brain MRI findings, including brain calcifications and periventricular cysts (Krenke et al., 2019). For a discussion of genetic heterogeneity of RILDBC, see RILDBC1 (613658).
Immunodeficiency 91 and hyperinflammation
MedGen UID:
1794283
Concept ID:
C5562073
Disease or Syndrome
Immunodeficiency-91 and hyperinflammation (IMD91) is an autosomal recessive complex immunologic disorder characterized by both immunodeficiency and recurrent infections, often to viruses or mycobacteria, as well as by hyperinflammation with systemic involvement. Affected individuals present in infancy with variable features, including fever, infection, thrombocytopenia, renal or hepatic dysfunction, recurrent infections, or seizures. Most patients eventually develop hepatic or renal failure, compromised neurologic function, lymphadenopathy or hepatosplenomegaly, and multiorgan failure resulting in death. More variable features may include intermittent monocytosis, features of hemophagocytic lymphohistiocytosis (HLH), and serologic evidence of hyperinflammation. The disorder is thought to result from dysregulation of the interferon response to viral stimulation in the innate immune system (summary by Le Voyer et al., 2021; Vavassori et al., 2021).
Knobloch syndrome 2
MedGen UID:
1812153
Concept ID:
C5676897
Disease or Syndrome
Knobloch syndrome-2 (KNO2) is characterized by severe vitreoretinal degeneration associated with occipital skull defects, ranging from mild encephalocele to abnormally pigmented hair. Developmental delay may be mild or severe (Antonarakis et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of Knobloch syndrome, see KNO1 (267750).
Respiratory infections, recurrent, and failure to thrive with or without diarrhea
MedGen UID:
1824079
Concept ID:
C5774306
Disease or Syndrome
Recurrent respiratory infections and failure to thrive with or without diarrhea (RIFTD) is characterized by neonatal onset of chronic cough, episodic wheezing, recurrent lower respiratory tract infections, chronic diarrhea, and failure to thrive. Despite the resemblance to cystic fibrosis (CF; 219700), these patients have normal sweat chloride and pancreatic elastase tests (Bertoli-Avella et al., 2022).

Professional guidelines

PubMed

Moncla LM, Briend M, Bossé Y, Mathieu P
Nat Rev Cardiol 2023 Aug;20(8):546-559. Epub 2023 Feb 24 doi: 10.1038/s41569-023-00845-7. PMID: 36829083
Patel H, Shah JR, Patel DR, Avanthika C, Jhaveri S, Gor K
Dis Mon 2023 Jul;69(7):101484. Epub 2022 Oct 9 doi: 10.1016/j.disamonth.2022.101484. PMID: 36220705
Ejima M, Okamoto T, Suzuki T, Anzai T, Takahashi K, Miyazaki Y
BMC Pulm Med 2021 Jul 19;21(1):243. doi: 10.1186/s12890-021-01608-1. PMID: 34281549Free PMC Article

Recent clinical studies

Etiology

Moncla LM, Briend M, Bossé Y, Mathieu P
Nat Rev Cardiol 2023 Aug;20(8):546-559. Epub 2023 Feb 24 doi: 10.1038/s41569-023-00845-7. PMID: 36829083
Hatabu H, Hunninghake GM, Richeldi L, Brown KK, Wells AU, Remy-Jardin M, Verschakelen J, Nicholson AG, Beasley MB, Christiani DC, San José Estépar R, Seo JB, Johkoh T, Sverzellati N, Ryerson CJ, Graham Barr R, Goo JM, Austin JHM, Powell CA, Lee KS, Inoue Y, Lynch DA
Lancet Respir Med 2020 Jul;8(7):726-737. doi: 10.1016/S2213-2600(20)30168-5. PMID: 32649920Free PMC Article
Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J
Nat Rev Dis Primers 2019 Jul 4;5(1):45. doi: 10.1038/s41572-019-0096-x. PMID: 31273209
Ma J, Rubin BK, Voynow JA
Chest 2018 Jul;154(1):169-176. Epub 2017 Nov 21 doi: 10.1016/j.chest.2017.11.008. PMID: 29170036
Lindman BR, Clavel MA, Mathieu P, Iung B, Lancellotti P, Otto CM, Pibarot P
Nat Rev Dis Primers 2016 Mar 3;2:16006. doi: 10.1038/nrdp.2016.6. PMID: 27188578Free PMC Article

Diagnosis

Alarcon-Calderon A, Vassallo R, Yi ES, Ryu JH
Immunol Allergy Clin North Am 2023 May;43(2):273-287. Epub 2023 Mar 1 doi: 10.1016/j.iac.2023.01.007. PMID: 37055089
Hatabu H, Hunninghake GM, Richeldi L, Brown KK, Wells AU, Remy-Jardin M, Verschakelen J, Nicholson AG, Beasley MB, Christiani DC, San José Estépar R, Seo JB, Johkoh T, Sverzellati N, Ryerson CJ, Graham Barr R, Goo JM, Austin JHM, Powell CA, Lee KS, Inoue Y, Lynch DA
Lancet Respir Med 2020 Jul;8(7):726-737. doi: 10.1016/S2213-2600(20)30168-5. PMID: 32649920Free PMC Article
Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J
Nat Rev Dis Primers 2019 Jul 4;5(1):45. doi: 10.1038/s41572-019-0096-x. PMID: 31273209
Spagnolo P, Rossi G, Trisolini R, Sverzellati N, Baughman RP, Wells AU
Lancet Respir Med 2018 May;6(5):389-402. Epub 2018 Apr 3 doi: 10.1016/S2213-2600(18)30064-X. PMID: 29625772
Raoof S, Bondalapati P, Vydyula R, Ryu JH, Gupta N, Raoof S, Galvin J, Rosen MJ, Lynch D, Travis W, Mehta S, Lazzaro R, Naidich D
Chest 2016 Oct;150(4):945-965. Epub 2016 May 13 doi: 10.1016/j.chest.2016.04.026. PMID: 27180915Free PMC Article

Therapy

Alarcon-Calderon A, Vassallo R, Yi ES, Ryu JH
Immunol Allergy Clin North Am 2023 May;43(2):273-287. Epub 2023 Mar 1 doi: 10.1016/j.iac.2023.01.007. PMID: 37055089
Phan THG, Paliogiannis P, Nasrallah GK, Giordo R, Eid AH, Fois AG, Zinellu A, Mangoni AA, Pintus G
Cell Mol Life Sci 2021 Mar;78(5):2031-2057. Epub 2020 Nov 17 doi: 10.1007/s00018-020-03693-7. PMID: 33201251Free PMC Article
Chua F, Desai SR, Nicholson AG, Devaraj A, Renzoni E, Rice A, Wells AU
Ann Am Thorac Soc 2019 Nov;16(11):1351-1359. doi: 10.1513/AnnalsATS.201902-181CME. PMID: 31425665Free PMC Article
Lindman BR, Clavel MA, Mathieu P, Iung B, Lancellotti P, Otto CM, Pibarot P
Nat Rev Dis Primers 2016 Mar 3;2:16006. doi: 10.1038/nrdp.2016.6. PMID: 27188578Free PMC Article
Craig VJ, Zhang L, Hagood JS, Owen CA
Am J Respir Cell Mol Biol 2015 Nov;53(5):585-600. doi: 10.1165/rcmb.2015-0020TR. PMID: 26121236Free PMC Article

Prognosis

Alarcon-Calderon A, Vassallo R, Yi ES, Ryu JH
Immunol Allergy Clin North Am 2023 May;43(2):273-287. Epub 2023 Mar 1 doi: 10.1016/j.iac.2023.01.007. PMID: 37055089
Lin W, Xin Z, Zhang J, Liu N, Ren X, Liu M, Su Y, Liu Y, Yang L, Guo S, Yang Y, Li Y, Cao J, Ning X, Li J, Xue H, Niu N, Chen Y, Li F, Sun L, Zhang X, Zhang F, Zhang W
BMC Pulm Med 2022 Feb 27;22(1):73. doi: 10.1186/s12890-022-01868-5. PMID: 35220958Free PMC Article
Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J
Nat Rev Dis Primers 2019 Jul 4;5(1):45. doi: 10.1038/s41572-019-0096-x. PMID: 31273209
Spagnolo P, Rossi G, Trisolini R, Sverzellati N, Baughman RP, Wells AU
Lancet Respir Med 2018 May;6(5):389-402. Epub 2018 Apr 3 doi: 10.1016/S2213-2600(18)30064-X. PMID: 29625772
Belloli EA, Beckford R, Hadley R, Flaherty KR
Respirology 2016 Feb;21(2):259-68. Epub 2015 Nov 13 doi: 10.1111/resp.12674. PMID: 26564810

Clinical prediction guides

Lin W, Xin Z, Zhang J, Liu N, Ren X, Liu M, Su Y, Liu Y, Yang L, Guo S, Yang Y, Li Y, Cao J, Ning X, Li J, Xue H, Niu N, Chen Y, Li F, Sun L, Zhang X, Zhang F, Zhang W
BMC Pulm Med 2022 Feb 27;22(1):73. doi: 10.1186/s12890-022-01868-5. PMID: 35220958Free PMC Article
Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J
Nat Rev Dis Primers 2019 Jul 4;5(1):45. doi: 10.1038/s41572-019-0096-x. PMID: 31273209
Spagnolo P, Rossi G, Trisolini R, Sverzellati N, Baughman RP, Wells AU
Lancet Respir Med 2018 May;6(5):389-402. Epub 2018 Apr 3 doi: 10.1016/S2213-2600(18)30064-X. PMID: 29625772
Ma J, Rubin BK, Voynow JA
Chest 2018 Jul;154(1):169-176. Epub 2017 Nov 21 doi: 10.1016/j.chest.2017.11.008. PMID: 29170036
Tarantino G, Esposito S, Andreozzi L, Bracci B, D'Errico F, Rigante D
Int J Mol Sci 2016 Dec 15;17(12) doi: 10.3390/ijms17122111. PMID: 27983684Free PMC Article

Recent systematic reviews

Alilou S, Zangiabadian M, Pouramini A, Jaberinezhad M, Shobeiri P, Ghozy S, Haseli S, Beizavi Z
Acad Radiol 2023 Dec;30(12):3076-3085. Epub 2023 Jun 6 doi: 10.1016/j.acra.2023.06.002. PMID: 37491177Free PMC Article
van Laar M, van Amsterdam WAC, van Lindert ASR, de Jong PA, Verhoeff JJC
Radiother Oncol 2020 Oct;151:152-175. Epub 2020 Jul 22 doi: 10.1016/j.radonc.2020.07.030. PMID: 32710990
Staub LJ, Mazzali Biscaro RR, Kaszubowski E, Maurici R
J Emerg Med 2019 Jan;56(1):53-69. Epub 2018 Oct 9 doi: 10.1016/j.jemermed.2018.09.009. PMID: 30314929
Gerami P, Walling HW, Lewis J, Doughty L, Sontheimer RD
Br J Dermatol 2007 Oct;157(4):637-44. Epub 2007 Jun 26 doi: 10.1111/j.1365-2133.2007.08055.x. PMID: 17596148
Barlési F, Villani P, Doddoli C, Gimenez C, Kleisbauer JP
Fundam Clin Pharmacol 2004 Feb;18(1):85-91. doi: 10.1046/j.0767-3981.2003.00206.x. PMID: 14748759

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