Chilblain lupus L93.2

Rare, acquired variant of cutaneous lupus erythematosus with acrally localized, cold-induced, pressure-dolent plaques reminiscent of pernions. The clinical and histological differentiation from true chilblain lupus is not always easy, although in the case of frostbite there is a direct temporal relation to exposure to cold, which is not always detectable in chilblain lupus.

Rare (Note: Chilblain lupus is often not diagnosed, so the epidemiological data may need correction); allegedly < 100 cases have been described since the first description.

So far unexplained.

A connection of microvascular stasis by cold-induced capillary damage and hyperviscosity caused by immunological phenomena is discussed. In this context, the occurrence of chiblain lupus-like changes in COVID-19 infections as well as after COVID vaccinations is noteworthy.

Links to anorexia nervosa have been described.

Further discussed are autosomal-dominantly inherited mutations in the TREX1 gene, a gene encoding an intracellular DNase (see Nucleases below), which itself plays a significant role in apoptosis. TREX1 is associated with familial chilblain lupus.

Occurs almost exclusively in women, especially in the cold season and in cooler latitudes. Precedes, co-occurs with, and follows other cutaneous manifestations of cutaneous or systemic lupus erythematosus.

A pseudo-chiblain is seen in the setting of COVID-19 infection (COVID toes) and is generally associated with a mild course of infection. Chiblain-like recurrences may also occur after COVID vaccination .

In the early stage, extensive, deep-red, in winter or the transitional seasons also blue, pressure-dolent swellings, plaques and nodules reminiscent of chilblain.

Over the course of years, reddish-livid, indistinct, distinctly indurated, hyperkeratotic plaques, either surface smooth or coarse lamellar scaling. Possibly hyperesthesia, central atrophy, also erosions or rhagades (over the dorsal parts of the finger joints) or also areal ulcers. A seasonal course is typical, with clear accentuation of the skin symptoms in the cold season and equally clear (but usually not complete) remission in the summer months.

In 2006, a familial form of Chilblain lupus was described for the first time, which is most frequently due to a mutaion of the TREX1 gene (see there).

Sign of cutaneous lupus erythematosus: Epidermis with localization-typical orthohyperkeratosis and slight or even distinct atrophy of the surface epithelium. Throughout the entire dermis dense perivascular lymphocellular infiltrates. In between numerous ectatic, thin-walled blood vessels. In the junctional zone, discrete vacuolar basal cell degeneration. In the mucin staining dermal mucin deposits detectable.

In the ideal case lupus-typical granular C3- IgG - and IgM deposits at the dermo-epidermal junction zone (lupus band) and at the papillary capillaries.

• major criteria:
  • Acral "chilblain-like" plaques
  • Fine tissue: Histological and immunohistological signs of LE
• Secondary criteria
  • Signs of systemic lupus erythematosus
  • Other cutaneous lesions (not localized to the hands and feet) of "Chilblain's lupus".
  • Proven sensitivity to cold
  • Cryoglobulins and cold agglutinins: neg
  • Improvement with antimalarial therapy.
• Note: Diagnosis confirmed by 2 major criteria and 1 minor criterion.

Frostbite (see below Pernio): most important differential diagnosis, not always reliably differentiable because clinically very similar, furthermore identical collective and identical localizations.

Notice. There is no evidence of lupus erythematosus in perniones.

Sarcoidosis (Lupus pernio): localized mainly in the face (nose); rather untypical localization for Chilblain's lupus. Histology with epithelioid cellular granulomas is proving.

Thrombosis, more rarely cryoglobulinemia, macroglobulinemia or vasculitis.

Cave! Due to the risk of transformation into SLE, patients require regular clinical monitoring.

Consistent cold protection (see also scleroderma, systemic).

Local treatment with medium strength glucocorticoid ointments 0.25% prednicarbate ointment (e.g. Dermatop), 0.1% mometasone ointment (e.g. Ecural ointment), if necessary under occlusion.

Systemic immunosuppressive therapy should be avoided unless signs of systemic lupus erythematosus occur, in which case appropriate treatment modalities should be applied.

In the exclusively cutaneous form, therapy with chloroquine over several months is considered established (dosage corresponding to systemic lupus erythematosus).

Invasive treatment approaches such as chemical lumbar sympathectomy are being discussed.

Tendency to chronic course. In association with SLE, chilblain lupus occurs either before, with or after other manifestations of LE.

Case 1) A 34 -year-old female patient reported livid-red plaques on the fingers of both hands that had been present for about 1 decade, accentuated in winter, and markedly improved (but not healed) in the summer months. Recently also slightly painful nodules on the knees. Furthermore renal hypertension and excessive cigarette consumption (20 cigarettes per day). Findings: On both hands, here on the dorsum of the fingers 2-4 livid pressure-dolent swellings, plaques and nodules. Isolated hyperkeratotic nodules with central atrophy. Histology: Dense, perivascular lymphocellular infiltrates throughout the dermis shown. Interspersed are numerous ectatic, thin-walled blood vessels. In the junctional zone, discrete vacuolar basal cell degeneration. Detectable dermal mucin deposits in the mucin stain. Hypergammaglobulinemia. ANA: positive; anti SSA/Ro neg. ds-DNA: neg.; ESR 20/40mm; . Therapy: local treatment with medium strength glucocorticoid ointments at times under occlusion. Chloroquine (see below for dosage of antimalarials).

Case 2)

A 60-year-old, otherwise healthy patient described that she had noticed swollen, bursting fingers in the cold season for 10 years. Similar changes in feet and nose had occurred for 2-3 years. She noticed a significant worsening of the symptoms in winter. In summer, there was almost complete remission. She also noticed a significant improvement of the symptoms during a longer vacation trip to South Africa. However, when she returned to cold Germany, the problem reappeared within a few weeks. She was treated with a local cortisone preparation, which always brought about a short-term improvement. An internal treatment has not yet taken place. Findings: Large red and swollen, in cold weather also blue, painful fingers and back of the hand, dorsally intensified; over the back of the hand also streaky redness. Over the extensor sides of individual finger joints coarse scaling with rhagades. Nose and cheeks (butterfly-like) reddened and slightly swollen interspersed with telangiectasias (this is evaluated as rosacea erythematosa (!)). Histology: Vigorous edema of the upper and middle dermis, conspicuously dilated blood vessels. Superficial and deep nodular perivascular pure lymphocytic infiltrates. Focal epitheliotropy (including in the adnexal area). Patchy features of interface dermatitis. Epidermis orthokeratotic keratinizing. Laboratory: ESR 20/50mm; positive rheumatoid factor, ANA:1-320 positive; anti-Ro+; no DNA-Ak. Gamma globulins slightly elevated. Therapy: The patient initially received nifedipine p.o. without significant success. Subsequently, transition to chloroquine (see below for dosage of antimalarials). Local therapy: Strict cold protection, local corticosteroids if needed.

1. Franceschini F, et al (1999) Chilblain lupus erythematosus is associated with antibodies to SSA/Ro. Lupus 8: 215-219
2. Gambichler T et al (2022) Cutaneous findings following COVID-19 vaccination: review of world literature and own experience. J Eur Acad Dermatol Venereol 36:172-180.
3. Günther C (2015) Genetics of lupus erythematosus. Dermatol 66:121-130
4. Halermann C et al (2011) Painful livid plaques on the acras in cold. JDDG 9: 331-332
5. Helm TN, Jones CM (2002) Chilblain lupus erythematosus lesions precipitated by the cold. Cutis 69: 183-184
6. Hutchinson J (1
7. 888) Harveian lectures on lupus. The varieties of common lupus. Br Med J 58: 113-118
8. Lee-Kirsch MA 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
9. Lee-Kirsch MA et al (2006) Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p. Am J Hum Genet 79: 731-737.
10. Millard LG et al (1987) Chilblain lupus erythematosus. Br J Dermatol 98: 497-506.
11. Pistorius MA et al (2020) Chilblains and COVID19 infection: Causality or coincidence? How to proceed? J Med Vasc 45:221-223.
12. Shaikh TG et al. (2022) SARS-CoV-2 Vaccination and Chilblain-like Lesions: What Do We Know so Far? Dermatol Pract Concept 12:e2022170.
13. Su WP et al (1994) Chilblain lupus erythematosus (lupus pernio): clinical review of the Mayo Clinic erxperience and proposal of diagnostic criteria. Cutis 54: 395-399
14. Uter W et al (1988) Chilblain lupus erythematosus. Dermatologist 39: 602-605