Chilblain lupus erythematosus

Author(s): Matthew James Verheyden, Medical Student, University of Notre Dame Australia, Sydney, NSW, Australia; Claudia Hadlow, Medical Student, University of Notre Dame Australia, Sydney, NSW, Australia. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. August 2019.


What is chilblain lupus erythematosus?

Chilblain lupus erythematosus (LE) is a rare variant of chronic cutaneous LE and was originally described by Jonathan Hutchinson in 1888 [1].

The term ‘chilblain’ is derived from Anglo-Saxon terms ‘chill’ referring to ‘cold’ and ‘blegen’, which is a synonym for ‘sore’.

Lupus chilbains

Who gets chilblain lupus erythematosus?

Chilblain LE is an under-recognised entity. In a 2008 review, the authors stated that 70 cases have been reported in the literature, with limited numbers of adolescents [2].

Chilblain LE occurs as a sporadic and inherited condition. Sporadic cases are the most common and occur predominantly in middle-aged females [3]. Familial chilblain LE presents in early childhood [4].

Associations with anorexia nervosa, intestinal lymphoma, and pregnancy have been described in the literature.

What causes chilblain lupus erythematosus?

The pathogenesis of the sporadic form of chilblain LE remains unknown [2].

It is believed that cold stimulus provokes vasoconstriction or microvascular injury with occlusion of the capillary bed and diminished circulation, leading to hyperviscosity and stasis of the skin, which is exacerbated by reduced blood temperature [2,3].

These pathophysiological changes in the flow and microvasculature may also be aggravated by immunological anomalies (eg, rheumatoid factor or autoantibodies).

In those with a family history, or onset of chilblain LE in childhood, the condition may be a result of a mutation in the TREX1 or SAMHD1 genes [5].

  • TREX1 is a gene located on chromosome 3 that encodes a nuclear protein with a role in DNA repair and proofreading for DNA polymerase.
  • SAMHD1 is a gene located on chromosome 20 that encodes a host restriction nuclease with a role in the innate immune response.

These mutations in TREX1 and SAMHD1 are inherited via an autosomal dominant mode of inheritance [4,6]. Heterozygous mutation (a mutation of one allele) in these genes lead to accumulation of nucleic acids (eg, dsDNA, RNA:DNA duplexes).

TREX1 mutations have also been described in other conditions related to microvascular endothelial dysfunction, such as dominant retinal vasculopathy and cerebral leukodystrophy.

What are the clinical features of chilblain lupus erythematosus?

Chilblain LE begins as red or dusky purple patches, papules, and plaques that are initiated or exacerbated by exposure to cold and moisture in a cool climate. The lesions are often pruritic and painful.

The common sites involved are the fingers, toes, heels, and soles. Less frequently, the lesions may also be present on the nose, ears, palms, knuckles, elbows, knees, and lower legs.

Other features may include:

People living in regions with warmer and drier climates may not develop typical chilblains.

In some circumstances, chilblains may represent lupus pernio with pre-existing LE rather than chilblain LE [7]. In these cases, although the two entities are clinically similar and both associated with systemic disease (sarcoidosis and systemic lupus erythematosus, respectively), the prognosis and treatment regimens are distinct [7].

What are the complications of chilblain lupus erythematosus?

Complications of chilblain LE include:

Follow-up is advised for those with features of SLE (eg, malar rash).

How is chilblain lupus erythematosus diagnosed?

The Mayo Clinic Diagnostic Criteria for the diagnosis of chilblain LE comprises of two major, and four minor criteria [8]. In order to diagnose chilblain LE, both major criteria and at least one minor criterion need to be demonstrated.

Major criteria

  • Lesions in acral locations induced by exposure to cold or any decrease in temperature
  • Evidence of LE in the skin lesions by histopathological examination or indirect immunofluorescence study
    • A superficial and deep lymphocytic vascular reaction
    • Fibrin deposition in reticular, dermal-based blood vessels
    • Interface dermatitis with degeneration of dermoepidermal junction with an accumulation of IgM, IgA, and C3.

Minor criteria

  • Coexistence of SLE or other forms of cutaneous LE
  • Response to anti-LE therapy
  • Negative results of cryoglobulin and cold agglutinin studies.

Chilblain LE is often be associated with several immunological makers including:

  • Anti-Ro/SS-A antibodies
  • Hypergammaglobulinemia
  • Rheumatoid factor
  • Anti-nuclear antibodies
  • Antiphospholipid antibodies
  • Positive latex agglutination tests [2].

Raynaud phenomenon may also coexist [2].

Lesions persisting beyond the colder months, positive antinuclear antibody, and concomitant features of the American College of Rheumatology (ACR) criteria for SLE distinguish chilblain LE from idiopathic chilblains [9].

What is the differential diagnosis for chilblain lupus erythematosus?

Other skin conditions that can be confused with chilblain lupus include perniosis (ordinary chilblains), acrocyanosis, Raynaud phenomenon, lupus pernio, livedo reticularis, cold panniculitis, and cold urticaria.

Perniosis

Perniosis (or usual chilblains) is characterised by:

  • A sensation of itching, burning, or pain
  • Symmetrical erythrocyanotic discolouration of acral skin
  • Non-specific histology comprising of dermal oedema with superficial and deep lymphohistiocytic infiltrate and perieccrine accentuation.

Acrocyanosis

Acrocyanosis is characterised by:

  • Painless lesions, in most cases
  • Dusky red to purple discolouration
  • Acral distribution.

Raynaud phenomenon

Raynaud phenomenon is characterised by:

  • The sequence of well-demarcated pallor, followed by blue, then red discolouration
  • Absence of ulceration (with the idiopathic form).

Livedo reticularis

Livedo reticularis is characterised by:

Cold panniculitis

Cold panniculitis is characterised by:

  • Erythematous, indurated plaques that develop at sites of cold exposure
  • Location on the cheeks and chin
  • Occurrence in children and young women
  • Resolution within two weeks.

Cold urticaria

Cold urticaria is a form of chronic inducible urticaria characterised by:

  • Cold-induced weals and angioedema
  • Systemic symptoms in some patients.

What is the treatment for chilblain lupus erythematosus?

General measures

Protection from the cold by various physical measures should be emphasised.

Examples of these measures include:

  • Avoidance of cold and moist environments, when possible
  • Ensuring that the home and workplace are well insulated and provide heating
  • Wearing gloves, thicken woollen socks, and comfortable protective footwear
  • Soaking hands in warm water to warm them up throughout the day
  • Engaging in physical activity to maintain central body temperature.

Smoking cessation should also be encouraged, due to vasoconstrictive effects of nicotine.

Medications

Medication may be necessary for patients with recalcitrant lesions and for secondary bacterial skin infections. A therapeutic approach has been proposed based on the level of evidence of the therapies in chilblain LE [2].

These include the following:

Surgery

Patients have successfully been treated in certain circumstances by excision and repair using a full-thickness graft derived from an unaffected area.

What is the outcome for chilblain lupus erythematosus?

The majority of patients respond well to symptomatic treatment.

In those with the sporadic form, 18% of individuals will eventually develop SLE; there is no evidence of progression to SLE in familial chilblain LE.

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References

  1. Hutchinson J. Harveian Lectures on Lupus. Br Med J 1888; 1: 113–8. doi: 10.1136/bmj.1.1412.113. PubMed Central
  2. Hedrich CM, Hauck FH, Sallmann S, Hahn G, Pfeiffer C, Heubner G, Lee-Kirsch MA, Gahr M. Chilblain lupus erythematosus--a review of literature. Clin Rheumatol 2008; 27: 947–54. doi: 10.1007/s10067-008-0942-9. PubMed
  3. Doutre MS, Beylot C, Beylot J, Pompougnac E, Royer P. Chilblain lupus erythematosus: report of 15 cases. Dermatology 1992; 184: 26–8. PubMed
  4. Lee-Kirsch MA, Chowdhury D, Harvey S, Gong M, Senenko L, Engel K, Pfeiffer C, Hollis T, Gahr M, Perrino FW, Lieberman J, Hubner N. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. Journal of Molecular Medicine 2007; 85: 531–7. doi: 10.1007/s00109-007-0199-9. PubMed
  5. Tüngler V, Silver RM, Walkenhorst H, Günther C, Lee-Kirsch MA. Inherited or de novo mutation affecting aspartate 18 of TREX1 results in either familial chilblain lupus or Aicardi–Goutières syndrome. Br J Dermatol 2012; 167: 212–4. doi: 10.1111/j.1365-2133.2012.10813.x. PubMed Central
  6. Lee-Kirsch MA, Gong M, Schulz H, Rüschendorf F, Stein A, Pfeiffer C, Ballarini A, Gahr M, Hubner N, Linné M. Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p. Am J Hum Genet 2006; 79: 731–7. doi: 10.1086/507848. PubMed Central
  7. Arias-Santiago SA, Girón-Prieto M-S, Callejas-Rubio J-L, Fernández-Pugnaire M-A, Ortego-Centeno N. Lupus pernio or chilblain lupus?: two different entities. Chest 2009; 136: 946–7. doi: 10.1378/chest.09-1005. PubMed
  8. Su WP, Perniciaro C, Rogers RS, 3rd, White JW, Jr. Chilblain lupus erythematosus (lupus pernio): clinical review of the Mayo Clinic experience and proposal of diagnostic criteria. Cutis 1994; 54: 395–9. PubMed
  9. Viguier M, Pinquier L, Cavelier-Balloy B, De La Salmonière P, Cordoliani F, Flageul B, Morel P, Dubertret L, Bachelez H. Clinical and histopathologic features and immunologic variables in patients with severe chilblains: a study of the relationship to lupus erythematosus. Medicine 2001; 80: 180–8. doi: 10.1097/00005792-200105000-00004. PubMed

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