Skip to main content


Log in

Chilblain lupus erythematosus—a review of literature

  • Review Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

An Erratum to this article was published on 25 July 2008


Chilblain lupus erythematosus (CHLE) is a rare, chronic form of cutaneous lupus erythematosus. Sporadic cases and two families with autosomal dominant-inherited CHLE have been reported. In familial CHLE, two missense mutations in TREX1 encoding the 3′–5′ repair exonuclease 1 were described in affected individuals. The pathogenesis of sporadic CHLE remains unknown. Up to 20% of patients develop systemic lupus erythematosus (SLE). An association with anorexia is discussed. In many cases, there is good response to symptomatic therapy. SLE therapeutics have good effects on SLE-typical symptoms but not on chilblains themselves. This article reviews the clinical presentation, pathogenesis, diagnosis and treatment of CHLE. As an index patient with unique features, we report a 13-year-old boy developing CHLE after anorexia nervosa. Sequencing of TREX1 was normal. With psychotherapeutic support for anorexia and after antibiotic therapy, topical steroids, physical warming and calcium channel blockers, the patient experienced significant relief. Improvement of phalangeal perfusion was demonstrated by angio-MRI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others



Aicardi–Goutières syndrome


body mass index


complement factor 3


chilblain lupus erythematosus


cutaneous lupus erythematosus


discoid lupus erythematosus


double-stranded DNA


heat shock protein 70




immunoglobulin A


immunoglobulin M


La/SSB antigen


lupus erythematosus


magnetic resonance imaging




Ro/SSB antigen


systemic lupus erythematosus


Sm antigen


single-stranded DNA


3′–5′repair exonuclease 1, synonym DNAse III


  1. Millard LG, Rowell NR (1978) Chilblain lupus erythematosus (Hutchinson). A clinical and laboratory study of 17 patients. Br J Dermatol 98:497–506

    Article  PubMed  CAS  Google Scholar 

  2. Doutre MS, Beylot C, Beylot J et al (1992) Chilblain lupus erythematosus: report of 15 cases. Dermatology 184:26–28

    Article  PubMed  CAS  Google Scholar 

  3. Su WPD, Perniciario C, Rogers RS et al (1994) Chilblain lupus erythematosus (lupus pernio): clinical review of the Mayo Clinic experience and proposal of diagnostic criteria. Cutis 54:395–399

    PubMed  CAS  Google Scholar 

  4. Hutchinson J (1888) Harveian lectures on lupus: the varieties of common lupus. Br Med J 1:58–63

    Google Scholar 

  5. Lee-Kirsch MA, Chowdhury D, Harwey S et al (2007) A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J Mol Med 85:531–537

    Article  PubMed  CAS  Google Scholar 

  6. Rice G, Newman WG, Dean J et al (2007) Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi–Goutieres syndrome. Am J Hum Genet 80:811–815

    Article  PubMed  CAS  Google Scholar 

  7. Fisher DA, Everett MA (1996) Violaceous rash of dorsal fingers in a woman. Diagnosis: chilblain lupus erythematosus (perniosis). Arch Dermatol 132:459–462

    Article  PubMed  CAS  Google Scholar 

  8. Kuhn A, Schuppe H-C, Ruzicka T et al (2000) Uncommon clinical manifestations of lupus erythematosus. Hautarzt 51:818–825

    Article  PubMed  CAS  Google Scholar 

  9. Pock L, Petrovská P, Becvár R et al (2001) Verrucous form of chilblain lupus erythematosus. J Eur Acad Dermatol Venereol 15:448–451

    Article  PubMed  CAS  Google Scholar 

  10. Boehm I (2001) Chilblain lupus erythematosus Hutchinson: successful treatment with mycophenolate mofetil. Arch Dermatol 137:235–236

    PubMed  CAS  Google Scholar 

  11. Lee-Kirsch MA, Gong M, Chowdhury D et al (2007) Mutations in the gene encoding the 3′–5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet 39:1065–1067

    Article  PubMed  CAS  Google Scholar 

  12. Goutières F (2005) Aicardi–Goutières syndrome. Brain Dev 27:201–206

    Article  PubMed  Google Scholar 

  13. Richards A, van den Maagdenberg AM, Jen JC et al (2007) C-terminal truncations in human 3′–5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet 39:1068–1070

    Article  PubMed  CAS  Google Scholar 

  14. Shearn MA, Epstein WV, Engleman EP (1963) Relationship of serum proteins and rheumatoid factor to serum viscosity in rheumatic disease. J Lab Clin Med 61:677–686

    PubMed  CAS  Google Scholar 

  15. Franceschini F, Calzavara-Pinton P, Valsecchi L et al (1999) Chilblain lupus erythematosus is associated with antibodies to SSA/Ro. Adv Exp Med Biol 455:167–171

    PubMed  CAS  Google Scholar 

  16. Herrera-Esparza R, Villalobos R, Bollain-Y-Goytia JJ et al (2006) Apoptosis and redistribution of the Ro autoantigen in Balb/c mouse like in subacute cutaneous lupus erythematosus. Clin Dev Immunol 13:163–166

    Article  PubMed  CAS  Google Scholar 

  17. Zhang J, Xu Z, Jin J et al (2000) Induction of Ro/SSA antigen expression on keratinocyte cell membrane by heat shock and phorbol 12-myristate 13-acetate as well as estradiol and ultraviolet B. J Dermatol Sci 24:92–98

    Article  PubMed  CAS  Google Scholar 

  18. Aoki T, Ishizawa T, Hozumi Y et al (1996) Chilblain lupus erythematosus of Hutchinson responding to surgical treatment: a report of two patients with anti-Ro/SS-A antibodies. Br J Dermatol 134:533–537

    Article  PubMed  CAS  Google Scholar 

  19. Simon TD, Soep JB, Hollister JR (2005) Pernio in pediatrics. Pediatrics 116:e472–e475

    Article  PubMed  Google Scholar 

  20. White KP, Rothe MJ, Milanese A et al (1994) Perniosis in association with anorexia nervosa. Pediatr Dermatol 11:1–5

    Article  PubMed  CAS  Google Scholar 

  21. Marks R, Baker H, Marten RH et al (1967) Chilblain lupus erythematosus as a manifestation of lymphoma. Proc R Soc Med 60:494–496

    PubMed  CAS  Google Scholar 

  22. Kelly JW, Dowling JP (1985) Pernio. A possible association with chronic myelomonocytic leukemia. Arch Dermatol 121:1048–1052

    Article  PubMed  CAS  Google Scholar 

  23. Belizna CC, Tron F, Joly P et al (2008) Outcome of essential cryofibrinogenaemia in a series of 61 patients. Rheumatology (Oxford) 47:205–207

    Article  CAS  Google Scholar 

  24. Franceschini F, Calvara-Pinton P, Quinzanini M et al (1999) Chilblain lupus erythematosus is associated with antibodies to SSA/Ro. Lupus 8:215–219

    Article  PubMed  CAS  Google Scholar 

  25. Allegue F, Alonso ML, Rocomora A et al (1988) Chilblain lupus erythematosus and antiphospholipid antibody syndrome. J Am Acad Dermatol 19:908–910

    Article  PubMed  CAS  Google Scholar 

  26. Uter W, Proksh E, Schauder S (1988) Chilblain lupus erythematodes. Hautarzt 39:602–605

    PubMed  CAS  Google Scholar 

  27. Rustin MHA, Newton JA, Smith NP et al (1989) The treatment of chilblains with nifedipine: the results of a pilot study, a double blind placebo controlled randomized study and a long term open trial. Br J Dermatol 120:267–274

    Article  PubMed  CAS  Google Scholar 

  28. Allison AC, Eugui EM (1993) Mycophenolate mofetil, a rationally designed immunosuppressive drug. Clin Transplant 7:96–112

    Google Scholar 

  29. Blaheta RA, Leckel K, Wittig B et al (1998) Inhibition of endothelial receptor expression and of T-cell ligand activity by mycophenolate mofetil. Transpl Immunol 6:251–259

    Article  PubMed  CAS  Google Scholar 

  30. Breathnach SM, Wells GC (1979) Chilblain lupus erythematosus with response to chemical sympathectomy. Br J Dermatol 101(Suppl 17):49–51

    PubMed  Google Scholar 

Download references


We thank Dr. Min Ae Lee-Kirsch for the genomic sequencing of the TREX1 gene and the helpful discussion.


No potential conflict of interest relevant to this article were reported by any of the authors (C.M. Hedrich, B. Fiebig, F.H. Hauck, S. Sallmann, G. Hahn, C. Pfeiffer, G. Heubner, M. Gahr).

Author information

Authors and Affiliations


Corresponding author

Correspondence to C. M. Hedrich.

Additional information

An erratum to this article can be found at

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hedrich, C.M., Fiebig, B., Hauck, F.H. et al. Chilblain lupus erythematosus—a review of literature. Clin Rheumatol 27, 949–954 (2008).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: