Chilblain lupus erythematosus (CHLE), also known as lupus pernio or Hutchinson lupus, is a rare, chronic form of cutaneous lupus erythematosus (CLE) characterized by cold-induced, erythematous to violaceous lesions typically located on acral regions such as the fingers, toes, ears, and nose. First described by Jonathan Hutchinson in 1888, CHLE is considered a subset of chronic CLE and can occur as an isolated condition (primary CHLE) or in association with systemic lupus erythematosus (SLE) (secondary CHLE).
Etiology and Pathophysiology
Genetic Predisposition
- Familial CHLE (Hutchinson-Gilford progeria-like syndrome):
- Associated with TREX1 gene mutations, leading to defective DNA repair and interferon (IFN) overproduction.
- Autosomal dominant inheritance pattern.
- Sporadic CHLE:
- Linked to cold hypersensitivity and abnormal vascular responses.
Immunological Mechanisms
- Type I Interferon Pathway Activation:
- Elevated IFN-? levels contribute to inflammation.
- Vascular Dysfunction:
- Cold exposure triggers vasospasm, leading to ischemia-reperfusion injury and inflammatory cytokine release.
Environmental Triggers
- Cold and damp climates exacerbate lesions.
- Raynaud’s phenomenon is commonly associated.
Clinical Features
Cutaneous Manifestations
- Location:
- Fingers and toes (most common)
- Ears, nose, heels (less common)
- Morphology:
- Erythematous to violaceous plaques
- Edema, ulceration, and fissuring in severe cases
- Hyperkeratotic or scaly lesions in chronic cases
- Symptoms:
- Pain, itching, burning
- Worsening in winter months
Systemic Associations
- ~20% of CHLE patients develop SLE (secondary CHLE).
- Overlap with other autoimmune diseases:
- Discoid lupus erythematosus (DLE)
- Sjögren’s syndrome
- Antiphospholipid syndrome
Diagnosis
Clinical Diagnosis
- Based on history of cold sensitivity and characteristic skin lesions.
Histopathology
- Perivascular and periadnexal lymphocytic infiltrates
- Interface dermatitis (epidermal-dermal junction inflammation)
- Dermal mucin deposition
Immunofluorescence
- Granular deposition of IgG/IgM and C3 at the dermoepidermal junction (lupus band test).
Laboratory Findings
- Antinuclear antibodies (ANA) (positive in ~50% of cases)
- Anti-Ro/SSA and anti-La/SSB antibodies (if associated with Sjögren’s)
- Cryoglobulins or cold agglutinins (rare)
Differential Diagnosis
| Condition | Key Distinguishing Features |
|---|---|
| Perniosis (chilblains) | No lupus-specific antibodies, no systemic involvement |
| Acrocyanosis | Persistent cyanosis, no ulceration |
| Frostbite | History of extreme cold exposure, necrosis |
| Raynaud’s phenomenon | Triphasic color changes, no fixed lesions |
| Vasculitis | Palpable purpura, systemic symptoms |
Management
A. General Measures
- Avoid cold exposure (gloves, warm footwear).
- Smoking cessation (worsens vascular dysfunction).
- Moisturizers to prevent fissuring.
B. Pharmacological Therapy
First-Line Treatments
- Topical corticosteroids (clobetasol propionate 0.05%)
- Calcineurin inhibitors (tacrolimus 0.1% ointment)
Second-Line Treatments
- Hydroxychloroquine (HCQ) (200–400 mg/day) – gold standard for CLE
- Calcium channel blockers (nifedipine 30–60 mg/day) for Raynaud’s
Refractory Cases
- Methotrexate (MTX) (7.5–25 mg/week)
- Mycophenolate mofetil (MMF) (1–3 g/day)
- JAK inhibitors (e.g., baricitinib) – emerging therapy
C. Biologic Therapies (Experimental)
- Belimumab (anti-BAFF monoclonal antibody)
- Anifrolumab (anti-IFNAR monoclonal antibody)
D. Surgical Management
- Laser therapy for persistent telangiectasias.
- Debridement for ulcerated lesions.
Prognosis
- Primary CHLE: Benign course, often responsive to therapy.
- Secondary CHLE (with SLE): Higher risk of systemic complications.
- Chronic cases: May lead to scarring, atrophy, or digital deformities.
Conclusion
Chilblain lupus erythematosus is a distinct, cold-induced variant of cutaneous lupus that requires careful differentiation from other acral dermatoses. While topical steroids and hydroxychloroquine remain the mainstay of treatment, emerging biologic therapies offer hope for refractory cases.
Key Takeaways
- Chilblain lupus erythematosus is a rare but important diagnosis in patients with cold-induced acral lesions.
- Rule out SLE in all Chilblain lupus erythematosus patients due to the risk of systemic progression.
- Multidisciplinary care (dermatology, rheumatology) is essential for optimal management.
Future research should focus on targeted therapies modulating the interferon pathway and vascular dysfunction in Chilblain lupus erythematosus.