What is the likely diagnosis and recommended work‑up for a patient with a livedo‑type rash, fatigue, brain fog, and skin tenderness?

Likely Diagnosis: Livedoid Vasculopathy or Livedo Racemosa with Underlying Systemic Disease

Based on your presentation of livedo-type pattern, fatigue, brain fog, and skin tenderness, you most likely have either livedoid vasculopathy or livedo racemosa secondary to an underlying hypercoagulable state, autoimmune disease, or thrombophilia, and require immediate comprehensive workup to identify the underlying cause and prevent irreversible complications. 1, 2

Critical Distinction: Livedo Racemosa vs. Livedo Reticularis

• Livedo racemosa is pathological and presents as a persistent, erythematous or violaceous discoloration in a broken, branched, discontinuous, and irregular pattern, which matches your description 2, 3
• This pattern is distinct from physiological livedo reticularis (cutis marmorata), which is benign and reversible with warming 3
• Livedo racemosa is associated with serious underlying conditions in 63.6% of cases, including thrombotic disorders, autoimmune diseases, and hypercoagulable states 2

Immediate Diagnostic Workup Required

Essential Laboratory Testing

• Complete blood count with differential to assess for cytopenias, thrombocytopenia, or hematological abnormalities 2
• Comprehensive thrombophilia panel including antiphospholipid antibodies (anticardiolipin, anti-β2-glycoprotein I, lupus anticoagulant), protein C, protein S, antithrombin III, factor V Leiden, prothrombin gene mutation 1, 2
• Autoimmune serologies including ANA, anti-dsDNA, complement levels (C3, C4), rheumatoid factor, anti-Ro/La antibodies to evaluate for systemic lupus erythematosus or other connective tissue diseases 2, 4
• Inflammatory markers including ESR, CRP, and ferritin to assess systemic inflammation 2
• Coagulation studies including PT/INR, aPTT, fibrinogen, and D-dimer 1

Essential Imaging and Tissue Diagnosis

• Skin biopsy from the affected livedo area is mandatory to confirm diagnosis and distinguish between thrombotic occlusion (30.3% of cases), intimal/subintimal thickening (21.2%), vasculitis (15.2%), or no histological abnormalities (33.3%) 2, 5
• Brain MRI with and without contrast is essential given your brain fog symptoms, as livedo racemosa can be associated with Sneddon's syndrome (cerebrovascular disease with livedo) or CNS involvement from systemic lupus erythematosus 3, 4

Most Likely Underlying Diagnoses to Consider

Primary Considerations (in order of likelihood)

1. Livedoid vasculopathy - characterized by the triad of livedo racemosa, painful ulceration (your skin tenderness), and atrophie blanche scars; affects women more commonly and is associated with hypercoagulable states in 80% of cases 1, 5

2. Antiphospholipid antibody syndrome - presents with livedo racemosa, thrombotic events (24.2% of livedo racemosa patients have thrombotic history), and neurological symptoms including cognitive dysfunction (your brain fog) 2, 3

3. Systemic lupus erythematosus - can present with livedo racemosa, fatigue, and neuropsychiatric symptoms including cognitive impairment 2, 3, 4

4. Sneddon's syndrome - defined by livedo racemosa plus cerebrovascular disease, which could explain your brain fog 2, 3

Secondary Considerations

• Cutaneous polyarteritis nodosa - presents with livedo racemosa and skin tenderness but typically with subcutaneous nodules 2
• Thrombophilia (inherited or acquired) - 24.2% of livedo racemosa patients have abnormal results for 2 or more thrombophilia tests 2
• Idiopathic livedo racemosa - diagnosed only after excluding all secondary causes, accounts for 36.4% of cases 2

Critical Management Principles

Immediate Treatment Considerations

• Do not delay treatment while awaiting complete workup if clinical suspicion is high for livedoid vasculopathy with active ulceration or severe symptoms 1, 5
• First-line therapy includes antiplatelet agents (aspirin) and/or anticoagulation (low molecular weight heparin or warfarin) along with general supportive measures including compression therapy and wound care 1, 5
• Early and appropriate treatment is essential to reduce pain and prevent development of irreversible porcelain-white atrophic scars (atrophie blanche) 1, 5

Treatment Algorithm Based on Underlying Cause

• If thrombophilia or antiphospholipid syndrome is identified: long-term anticoagulation with warfarin (target INR 2-3) or direct oral anticoagulants 1
• If autoimmune disease is identified: treat the underlying condition with immunosuppression as indicated, while continuing antiplatelet/anticoagulation therapy 1, 5
• If idiopathic after complete workup: antiplatelet therapy (aspirin or clopidogrel) plus pentoxifylline or cilostazol as vasodilators 1, 5
• For refractory cases: consider intravenous immunoglobulin, hyperbaric oxygen therapy, anabolic steroids (danazol), or immunomodulators 1

Common Pitfalls to Avoid

• Do not dismiss this as benign livedo reticularis - the presence of systemic symptoms (fatigue, brain fog) and skin tenderness strongly suggests pathological livedo racemosa requiring investigation 2, 3
• Do not delay skin biopsy - diagnosis is often delayed in most patients, leading to irreversible scarring 1, 5
• Do not assume idiopathic disease without complete workup - 63.6% have identifiable underlying causes that require specific treatment 2
• Do not overlook neurological evaluation - brain fog may represent cerebrovascular involvement requiring urgent neuroimaging and neurological consultation 3, 4

Expected Clinical Course

• Livedoid vasculopathy is chronic-recurrent with attacks that are often unpredictable but tend to worsen during summer months 1, 5
• Without treatment, progression to painful ulceration and permanent scarring is expected 1, 5
• With appropriate anticoagulation/antiplatelet therapy, pain reduction and prevention of new lesions can be achieved within weeks to months 1, 5