Chilblain Lupus: Symptoms, Types, Causes and Treatment

Chilblain lupus is a rare, chronic form of cutaneous lupus erythematosus that manifests with painful, purplish lesions on acral (extremity) areas, especially after exposure to cold. While often dismissed as a seasonal nuisance, chilblain lupus can be a sign of underlying autoimmune disease and, in some cases, a harbinger of systemic lupus erythematosus (SLE) or a genetically inherited interferonopathy. In this comprehensive article, we explore the symptoms, types, causes, and evolving treatment options for chilblain lupus, drawing on the latest research and clinical experience.

Symptoms of Chilblain Lupus

Chilblain lupus presents with a distinct constellation of symptoms, often mimicking common chilblains (perniosis) but with critical differences. Recognizing these symptoms is essential for timely diagnosis and management.

Symptom	Description	Affected Areas	Source(s)
Pain & Itching	Painful, itchy, or burning sensations	Toes, fingers, heels, calves	2 3 9 14
Color Changes	Purplish-red or bluish macules/plaques	Acral skin (extremities)	2 3 9 10
Swelling	Localized swelling, sometimes with edema	Digits, heels, ears, cheeks	3 8 9 10
Ulceration	Skin ulcerations in severe or chronic cases	Fingers, toes, acral sites	8 10 12

Table 1: Key Symptoms of Chilblain Lupus

Painful, Itchy, and Burning Sensations

The hallmark of chilblain lupus is the onset of painful and pruritic (itchy) lesions, often accompanied by a burning sensation. These symptoms are usually triggered or worsened by exposure to cold or damp environments and persist much longer than simple perniosis, sometimes lasting for weeks or months even after re-warming 2 3 9.

Purplish-Red or Bluish Lesions

Lesions typically appear as red to violet or bluish macules, papules, or plaques on acral areas—most commonly the fingers, toes, heels, and sometimes ears or cheeks 2 3 9 10. The color changes are due to inflammation and microvascular injury.

Swelling and Edema

These lesions may be accompanied by localized swelling, sometimes with visible edema of the skin and underlying tissue. This swelling adds to the discomfort and can occasionally limit movement of the affected digits 3 8 9.

Ulceration and Chronic Changes

In persistent or severe cases, especially in familial forms, the lesions may ulcerate, leading to open sores that are slow to heal. Chronic lesions can result in atrophy, scarring, or even mutilation of the affected area over time 8 10 12.

Associated Symptoms

• Arthralgias (joint pain): Some patients, particularly those with systemic involvement, report joint discomfort in conjunction with skin symptoms 8 12.
• Photosensitivity and facial discoid lupus: Some cases show overlap with other lupus skin manifestations, such as discoid lupus lesions on the face 2 9 14.
• Persistence beyond cold exposure: Unlike simple chilblains, chilblain lupus lesions often persist regardless of environmental temperature and may recur or remain chronic 2 3 9 11.

Types of Chilblain Lupus

Chilblain lupus is not a single entity—it comprises several clinically and genetically distinct subtypes. Understanding these types helps tailor management and anticipate potential complications.

Type/Variant	Distinguishing Features	Onset/Inheritance	Source(s)
Sporadic (Idiopathic)	Occurs without family history or systemic disease; may later reveal autoimmune background	Adult onset, mostly women	2 3 9 11
Associated with SLE/DLE	Occurs with or after discoid or systemic lupus erythematosus	Variable	2 9 14 11
Familial Chilblain Lupus	Autosomal dominant inheritance, early childhood onset, gene mutations	Hereditary, early onset	4 6 7 8 10 12

Table 2: Types and Variants of Chilblain Lupus

Sporadic (Idiopathic) Chilblain Lupus

Most cases are sporadic, presenting in adults—predominantly women—often without a family history or initial evidence of systemic disease. Over time, some of these patients may develop laboratory abnormalities or progress to systemic lupus 2 3 9 11.

Chilblain Lupus Associated with Systemic or Discoid Lupus

A significant subset of chilblain lupus patients has concurrent or previous discoid lupus erythematosus (DLE) or systemic lupus erythematosus (SLE). In these cases, chilblain manifestations may be the first or only sign of lupus, or may occur alongside more classic lupus features 2 9 14.

• Overlap with DLE: Skin biopsies of chilblain lupus often show features identical to discoid lupus, and lesions may coexist on the face and acral sites 2 14.
• Risk of progression: The risk of developing SLE is higher in patients with both facial and acral lupus lesions 2 9 11.

Familial Chilblain Lupus

This rare, monogenic form presents in childhood and is inherited in an autosomal dominant pattern. It is caused by mutations in genes involved in DNA sensing and type I interferon signaling (e.g., TREX1, SAMHD1, STING). Familial chilblain lupus is characterized by severe, cold-induced cutaneous lesions and sometimes joint involvement, but usually lacks major organ disease 4 6 7 8 10 12.

• Clinical features: Painful, bluish-red lesions often ulcerate; onset is in early childhood; family history is positive 8 10 12.
• Genetic basis: Mutations in TREX1, SAMHD1, or STING; these drive excessive type I interferon signaling 4 6 7 8 12.
• Systemic features: Some patients may develop mild systemic symptoms, such as arthralgia, but most lack full SLE criteria 8 10 12.

Causes of Chilblain Lupus

The causes of chilblain lupus are multifactorial, ranging from environmental triggers and immune dysregulation to genetic mutations in familial cases. Understanding these mechanisms is crucial for diagnosis and management.

Cause/Mechanism	Role in Disease	Associated Types	Source(s)
Cold Exposure	Triggers microvascular injury/inflammation	All types (especially sporadic)	3 9 14
Autoimmune Abnormalities	Autoantibody formation, immune complex deposition	Sporadic, SLE/DLE-associated	2 9 5 11
Genetic Mutations	Mutations in TREX1, SAMHD1, STING, etc.; drive type I IFN overproduction	Familial form	4 6 7 8 10 12

Table 3: Causes and Mechanisms of Chilblain Lupus

Cold-Induced Microvascular Injury

Cold and damp exposure are key environmental triggers. They cause microvascular stasis and injury, especially in predisposed individuals, leading to the characteristic skin lesions of chilblain lupus 3 9 14. In familial and autoimmune forms, this process is exaggerated by underlying immune dysfunction.

Autoimmune Mechanisms

• Autoantibodies: Many patients with chilblain lupus, especially those with SLE or DLE, have circulating antinuclear antibodies and other lupus-associated autoantibodies (anti-dsDNA, anti-Sm, anti-RNP, anti-SSA/Ro, anti-SSB/La) 2 5 9 11.
• Immune complex deposition: Skin biopsies often reveal immune complexes and complement along the basement membrane, consistent with lupus pathogenesis 2 9 8.
• Risk of systemic disease: Chilblain lupus can be the first or only sign of underlying SLE or antiphospholipid antibody syndrome; careful follow-up and laboratory screening are advised 5 11.

Genetic Factors: Familial Chilblain Lupus

Familial forms are caused by heterozygous mutations in genes regulating DNA sensing and the type I interferon pathway:

• TREX1: The most common gene mutated in familial chilblain lupus. TREX1 encodes a DNA exonuclease; its deficiency leads to accumulation of DNA fragments, triggering chronic type I interferon release and skin inflammation 4 6 8 10 12.
• SAMHD1 and STING: Mutations in these genes have also been linked to familial chilblain lupus, similarly resulting in overactive interferon responses 4 7.
• Interferonopathy: These genetic defects are classified as type I interferonopathies, a group of diseases marked by excessive, chronic interferon signaling driving autoimmunity and inflammation 4 7 15.

Other Contributing Factors

• Female predominance: Sporadic chilblain lupus is more common in women, possibly due to hormonal or genetic susceptibility 2 9 11.
• Other autoimmune markers: Elevated gammaglobulins and rheumatoid factor may be found 9.
• Vascular and hematologic abnormalities: Rarely, chilblain lupus may be associated with antiphospholipid antibodies and, in some cases, antiphospholipid syndrome 5.

Treatment of Chilblain Lupus

Managing chilblain lupus can be challenging, as traditional lupus therapies are often less effective for acral lesions. Recent advances, especially for familial forms, are offering new hope.

Therapy	Main Effect/Mechanism	Typical Indications	Source(s)
Cold Avoidance & Protection	Prevents lesion development	All types	3 9 14
Antimalarials (e.g., hydroxychloroquine)	Immunomodulation	SLE/DLE-associated, sporadic	14
Corticosteroids	Suppresses inflammation	Severe or refractory cases	14
Pentoxifylline/Dapsone	Microvascular and immune effects	Select cases	14
JAK Inhibitors (e.g., baricitinib, ruxolitinib, tofacitinib)	Blocks type I IFN signaling	Familial/interferonopathy forms	4 7 13 15 16
Regular Monitoring	Early detection of systemic disease	All patients with chronic lesions	5 11

Table 4: Treatment Strategies for Chilblain Lupus

General Measures: Cold Avoidance

The first and most important step in management is minimizing exposure to cold and damp conditions. Patients are advised to keep extremities warm and dry, and to avoid rapid temperature changes 3 9 14.

Topical and Systemic Therapies

• Antimalarials: Drugs like hydroxychloroquine are commonly used in cutaneous lupus and may help some chilblain lupus patients, though response is often slower than for classic discoid lesions 14.
• Corticosteroids: Topical or systemic steroids may be used for severe inflammation but are generally less effective for persistent acral lesions 14.
• Pentoxifylline and Dapsone: These may be tried in select patients for their microvascular and immunomodulatory effects 14.

JAK Inhibitors: Targeted Therapy for Familial and Refractory Cases

A breakthrough in the management of familial chilblain lupus and other interferonopathies has been the use of Janus kinase (JAK) inhibitors (e.g., baricitinib, ruxolitinib, tofacitinib) 4 7 13 15 16:

• Mechanism: JAK inhibitors block the downstream signaling of type I interferon, reducing inflammation at the genetic and cellular level 13 16.
• Clinical results: Recent case series and reports demonstrate significant improvement of skin lesions, reduction in pain, and suppression of systemic interferon signatures in patients with TREX1 mutations treated with JAK inhibitors 15 16.
• Safety: So far, these agents have been well-tolerated in published cases, but long-term safety data are still being gathered 15 16.

Monitoring and Follow-Up

Given the risk of progression to systemic lupus or the development of associated autoimmune syndromes (such as antiphospholipid antibody syndrome), patients with chronic or recurrent chilblain lupus require regular monitoring:

• Blood tests: Screen for autoantibodies, complement levels, and renal involvement 5 11.
• Clinical surveillance: Watch for new symptoms such as joint pain, photosensitivity, or systemic manifestations 5 11.

Special Considerations

• Familial cases: Early referral for genetic counseling and consideration of targeted therapies is recommended 4 7 15.
• Refractory cases: For those not responding to standard therapies, JAK inhibitors or participation in clinical trials may be considered 13 15 16.
• Pediatric patients: Familial forms may present in children and should not be dismissed as simple perniosis 8 10 12.

Conclusion

Chilblain lupus is a complex, multifaceted disease that bridges the worlds of dermatology, rheumatology, and genetics. While often triggered by cold, its persistence and recurrence should prompt evaluation for underlying autoimmune disease or, in rare cases, genetic interferonopathy. Advances in genetics and immunology are reshaping treatment, especially for familial forms.

Key Takeaways:

• Chilblain lupus presents as painful, purplish lesions on the extremities, often triggered by cold but persisting chronically.
• There are sporadic, autoimmune-associated, and familial (genetic) types, each with distinct clinical and therapeutic implications.
• Causes range from microvascular injury and autoimmunity to mutations in interferon pathway genes.
• Treatment centers on cold avoidance, immunomodulatory drugs, and, in familial cases, JAK inhibitors that target interferon signaling.
• Ongoing monitoring is vital, as some patients may develop systemic lupus or related autoimmune syndromes.

By recognizing the unique features of chilblain lupus and staying informed about evolving therapies, clinicians and patients alike can achieve better outcomes and, importantly, avoid the pitfalls of delayed diagnosis.