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Chilblain lupus 1(CHBL1)

MedGen UID:
9822
•Concept ID:
C0024145
•
Disease or Syndrome
Synonym: CHBL1
 
Gene (location): TREX1 (3p21.31)
 
Monarch Initiative: MONDO:0012500
OMIM®: 610448

Definition

Chilblain lupus is a cutaneous form of systemic lupus erythematosus (SLE; 152700) characterized by the appearance of painful bluish-red papular or nodular lesions of the skin in acral locations (including the dorsal aspects of fingers and toes, heels, nose, cheeks, ears, and, in some cases, knees) precipitated by cold and wet exposure (summary by Lee-Kirsch et al., 2006). Genetic Heterogeneity of Chilblain Lupus See also CHBL2 (614415), caused by mutation in the SAMHD1 gene (606754) on chromosome 20q11. Mutations in the TREX1 and SAMHD1 genes also cause Aicardi-Goutieres syndrome (AGS1, 225750 and AGS5, 612952, respectively). [from OMIM]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
•Concept ID:
C0003862
•
Sign or Symptom
Joint pain.
See: Feature record | Search on this feature
Autoamputation of digits
MedGen UID:
343770
•Concept ID:
C1852289
•
Finding
The spontaneous detachment of a digit (finger or toe) from the body due to long standing pathology.
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Raynaud phenomenon
MedGen UID:
20474
•Concept ID:
C0034735
•
Disease or Syndrome
An episodic vasoconstriction resulting in discoloration of the skin and pain in the affected areas, often involving fingers or toes. Classically associated with triphasic color changes (white, blue, red) but may be biphasic. Often occurs in response to cold temperatures or emotional stress. May be primary or secondary to an underlying autoimmune disease.
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Chilblains
MedGen UID:
886
•Concept ID:
C0008058
•
Injury or Poisoning
Chilblains, also called perniosis, are an inflammatory skin condition related to an abnormal vascular response to the cold. We are unaware of a reliable estimate of incidence. It typically presents as tender, pruritic red or bluish lesions located symmetrically on the dorsal aspect of the fingers, toes, ears and nose. Less commonly, reports describe involvement of the thighs and buttocks. The lesions present hours after exposure to cold and usually resolve spontaneously in one to three weeks.
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Antinuclear antibody positivity
MedGen UID:
101792
•Concept ID:
C0151480
•
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
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Elevated erythrocyte sedimentation rate
MedGen UID:
57727
•Concept ID:
C0151632
•
Finding
An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
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Skin ulcer
MedGen UID:
52369
•Concept ID:
C0037299
•
Disease or Syndrome
A discontinuity of the skin exhibiting complete loss of the epidermis and often portions of the dermis and even subcutaneous fat.
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Cutaneous photosensitivity
MedGen UID:
87601
•Concept ID:
C0349506
•
Pathologic Function
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
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Abnormality of the nail
MedGen UID:
163115
•Concept ID:
C0853087
•
Anatomical Abnormality
Abnormality of the nail.
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Recent clinical studies

Etiology

Cutaneous signs in COVID-19 patients: A review.
Wollina U, Karadağ AS, Rowland-Payne C, Chiriac A, Lotti T
Dermatol Ther 2020 Sep;33(5):e13549. Epub 2020 May 29 doi: 10.1111/dth.13549. PMID: 32390279Free PMC Article
JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis.
Fragoulis GE, McInnes IB, Siebert S
Rheumatology (Oxford) 2019 Feb 1;58(Suppl 1):i43-i54. doi: 10.1093/rheumatology/key276. PMID: 30806709Free PMC Article
Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and TREX1 Mutation.
Zimmermann N, Wolf C, Schwenke R, Lüth A, Schmidt F, Engel K, Lee-Kirsch MA, Günther C
JAMA Dermatol 2019 Mar 1;155(3):342-346. doi: 10.1001/jamadermatol.2018.5077. PMID: 30673078Free PMC Article
Familial Chilblain Lupus - What Can We Learn from Type I Interferonopathies?
Fiehn C
Curr Rheumatol Rep 2017 Aug 26;19(10):61. doi: 10.1007/s11926-017-0689-x. PMID: 28844088
Innate immune processes in lupus erythematosus.
Aringer M, Günther C, Lee-Kirsch MA
Clin Immunol 2013 Jun;147(3):216-22. Epub 2012 Dec 12 doi: 10.1016/j.clim.2012.11.012. PMID: 23290784

Diagnosis

Cutaneous signs in COVID-19 patients: A review.
Wollina U, Karadağ AS, Rowland-Payne C, Chiriac A, Lotti T
Dermatol Ther 2020 Sep;33(5):e13549. Epub 2020 May 29 doi: 10.1111/dth.13549. PMID: 32390279Free PMC Article
Hydroxychloroquine-Associated Hyperpigmentation in Chilblain Lupus Erythematosus.
Horino T, Ichii O, Terada Y
J Clin Rheumatol 2020 Sep;26(6):e192. doi: 10.1097/RHU.0000000000001061. PMID: 31116124
Familial Chilblain Lupus - What Can We Learn from Type I Interferonopathies?
Fiehn C
Curr Rheumatol Rep 2017 Aug 26;19(10):61. doi: 10.1007/s11926-017-0689-x. PMID: 28844088
Chilblain lupus erythematosus.
Patel S, Hardo F
BMJ Case Rep 2013 Nov 27;2013 doi: 10.1136/bcr-2013-201165. PMID: 24285807Free PMC Article
Chilblain lupus induced by TNF-α antagonists: a case report and literature review.
Sifuentes Giraldo WA, Ahijón Lana M, García Villanueva MJ, González García C, Vázquez Diaz M
Clin Rheumatol 2012 Mar;31(3):563-8. Epub 2011 Dec 30 doi: 10.1007/s10067-011-1924-x. PMID: 22207249

Therapy

Hydroxychloroquine-Associated Hyperpigmentation in Chilblain Lupus Erythematosus.
Horino T, Ichii O, Terada Y
J Clin Rheumatol 2020 Sep;26(6):e192. doi: 10.1097/RHU.0000000000001061. PMID: 31116124
JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis.
Fragoulis GE, McInnes IB, Siebert S
Rheumatology (Oxford) 2019 Feb 1;58(Suppl 1):i43-i54. doi: 10.1093/rheumatology/key276. PMID: 30806709Free PMC Article
Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and TREX1 Mutation.
Zimmermann N, Wolf C, Schwenke R, Lüth A, Schmidt F, Engel K, Lee-Kirsch MA, Günther C
JAMA Dermatol 2019 Mar 1;155(3):342-346. doi: 10.1001/jamadermatol.2018.5077. PMID: 30673078Free PMC Article
Chilblain lupus erythematosus.
Patel S, Hardo F
BMJ Case Rep 2013 Nov 27;2013 doi: 10.1136/bcr-2013-201165. PMID: 24285807Free PMC Article
Chilblain lupus induced by TNF-α antagonists: a case report and literature review.
Sifuentes Giraldo WA, Ahijón Lana M, García Villanueva MJ, González García C, Vázquez Diaz M
Clin Rheumatol 2012 Mar;31(3):563-8. Epub 2011 Dec 30 doi: 10.1007/s10067-011-1924-x. PMID: 22207249

Prognosis

Cutaneous signs in COVID-19 patients: A review.
Wollina U, Karadağ AS, Rowland-Payne C, Chiriac A, Lotti T
Dermatol Ther 2020 Sep;33(5):e13549. Epub 2020 May 29 doi: 10.1111/dth.13549. PMID: 32390279Free PMC Article
Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and TREX1 Mutation.
Zimmermann N, Wolf C, Schwenke R, Lüth A, Schmidt F, Engel K, Lee-Kirsch MA, Günther C
JAMA Dermatol 2019 Mar 1;155(3):342-346. doi: 10.1001/jamadermatol.2018.5077. PMID: 30673078Free PMC Article
Comparative Analysis of Chilblain Lupus Erythematosus and Idiopathic Perniosis: Histopathologic Features and Immunohistochemistry for CD123 and CD30.
Wang ML, Chan MP
Am J Dermatopathol 2018 Apr;40(4):265-271. doi: 10.1097/DAD.0000000000000945. PMID: 28719438
Cold-Associated Perniosis of the Thighs ("Equestrian-Type" Chilblain): A Reappraisal Based on a Clinicopathologic and Immunohistochemical Study of 6 Cases.
Ferrara G, Cerroni L
Am J Dermatopathol 2016 Oct;38(10):726-31. doi: 10.1097/DAD.0000000000000477. PMID: 26885604
Systemic involvement in TREX1-associated familial chilblain lupus.
Günther C, Hillebrand M, Brunk J, Lee-Kirsch MA
J Am Acad Dermatol 2013 Oct;69(4):e179-81. doi: 10.1016/j.jaad.2013.04.020. PMID: 24034389

Clinical prediction guides

Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus.
David C, Arango-Franco CA, Badonyi M, Fouchet J, Rice GI, Didry-Barca B, Maisonneuve L, Seabra L, Kechiche R, Masson C, Cobat A, Abel L, Talouarn E, Béziat V, Deswarte C, Livingstone K, Paul C, Malik G, Ross A, Adam J, Walsh J, Kumar S, Bonnet D, Bodemer C, Bader-Meunier B, Marsh JA, Casanova JL, Crow YJ, Manoury B, Frémond ML, Bohlen J, Lepelley A
J Exp Med 2024 Aug 5;221(8) Epub 2024 Jun 13 doi: 10.1084/jem.20232066. PMID: 38869500Free PMC Article
Comparative Analysis of Chilblain Lupus Erythematosus and Idiopathic Perniosis: Histopathologic Features and Immunohistochemistry for CD123 and CD30.
Wang ML, Chan MP
Am J Dermatopathol 2018 Apr;40(4):265-271. doi: 10.1097/DAD.0000000000000945. PMID: 28719438
Cold-Associated Perniosis of the Thighs ("Equestrian-Type" Chilblain): A Reappraisal Based on a Clinicopathologic and Immunohistochemical Study of 6 Cases.
Ferrara G, Cerroni L
Am J Dermatopathol 2016 Oct;38(10):726-31. doi: 10.1097/DAD.0000000000000477. PMID: 26885604
Exonuclease TREX1 degrades double-stranded DNA to prevent spontaneous lupus-like inflammatory disease.
Grieves JL, Fye JM, Harvey S, Grayson JM, Hollis T, Perrino FW
Proc Natl Acad Sci U S A 2015 Apr 21;112(16):5117-22. Epub 2015 Apr 6 doi: 10.1073/pnas.1423804112. PMID: 25848017Free PMC Article
Familial chilblain lupus due to a novel mutation in the exonuclease III domain of 3' repair exonuclease 1 (TREX1).
Günther C, Berndt N, Wolf C, Lee-Kirsch MA
JAMA Dermatol 2015 Apr;151(4):426-31. doi: 10.1001/jamadermatol.2014.3438. PMID: 25517357

Supplemental Content

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    Clinical resources

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    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • MeSH
      Related Medical Subject Headings
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

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