An 8-year old girl consulted our department concerning a painful dermatosis on the hands and feet. She described the lesions as small painful skin lesions which evolved to little erosions and wounds. After some time it resolved spontaneously, but recurrence was noted. The patient experienced a worsening during cold temperatures. Based on the anamnesis and the findings at the clinical examination, a differential diagnosis of pernio (chilblains), vasculitis and cryoglobulinemia was made.
She has been in follow-up by a pediatrician because of walking problems and spasticity since the age of 18 months. On an MRI of the brain, periventricular white matter lesions were seen, however without any known cause.
At the time of consultation, she presented with erythematous/purplish papules and plaques on fingers and toes with peri-ungual involvement. Nail fold capillaroscopy was normal. Laboratory tests revealed a discrete elevation of liver enzymes and positive antinuclear antibodies (1:320). A 4-mm punch biopsy from an erythematous plaque on the finger was performed for histological analysis, leading to the diagnosis of lupus erythematosus (LE), more specifically chilblain lupus erythematosus (CHLE).
CHLE is a rare, chronic variant of lupus erythematosus, sometimes associated with other forms of cutaneous or systemic lupus erythematosus. It can present as a sporadic or as an autosomal inherited form.
The patient was referred to the pediatric rheumatologist for further review and genetic analysis. A SAHMD-1 mutation was found, responsible for the Aicardi-Goutières syndrome. The Aicardi-Goutières syndrome is an inherited encephalopathy that affects newborn infants and usually results in severe mental and physical handicap. There are two forms of the syndrome: an early-onset form that is severe, and a late-onset form that has less impact upon neurological function. Interestingly, up to 40% of patients affected by Aicardi-Goutières syndrome experience CHLE-like lesions.
Mutations in SAMHD-1, for example in the Aicardi-Goutières syndrome, are characterized by an aberrant production of type I interferon (interferon-α and interferon-β). Type I interferon is suggested to be toxic to the central nervous system, especially during early neurological development. Previous treatments with topical corticosteroids, hydroxychloroquine or nifedipine did not cause any improvement. A treatment with Tofacitinib, a Janus kinase (JAK) 1/3 inhibitor, which, via the JAK-STAT mechanism, is thought to suppress the systemic type I interferon activation, has been started. Since the treatment with Tofacitinib was initiated, the patient and her parents noted an improvement of the lesions. The liver function tests are also normalized.
References
- Damsky W. et al. Targeted Treatment of TREX1 Chilblain Lupus and Other Interferonopathies – Taming TREX. JAMA Dermatology. 2019;155(3):283-284
- Damsky W. et al. JAK inhibitors in dermatology: the promise of a new drug class. Journal of the American Academy of Dermatolgy. 2017;76(4):736-744
- König N. et al. Familial chilblain lupus due to a gain-of-function mutation in STING. Annals of the Rheumatic Diseases. 2017;76(2):468-472
- Crow Y. et al. Therapies in Aicardi-Goutières syndrome. British Society for Immunology, Clinical and Experimental Immunology. 2013;175:1-8
- Crow Y. Aicardi-Goutières syndrome. Handbook of Clinical Neurology. 2013;113:1629-1635
- Crow Y. Aicardi-Goutières Syndrome. GeneReviews. 2005 (online, updated November 2016)
Pyl J. 1, 2, Ogunjimi B. 2, 3, Leysen J. 1, 2, De Moor A. 1, Dandelooy J. 1
1 Department of Dermatology, Antwerp University Hospital, Edegem, Belgium.
2 University of Antwerp, Antwerp, Belgium.
3 Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium.