What are the next steps for a patient with a history of psoriasis, treated with Skyrizi (risankizumab), who reports hot, burning, and red feet at night for 2 years, and is currently taking Gabapentin and Klonopin, with a negative rheumatology workup?

Evaluation and Management of Burning Feet in a Psoriasis Patient on Skyrizi

Primary Assessment: Rule Out Small Fiber Neuropathy

The most critical next step is to evaluate for small fiber neuropathy (SFN) through skin biopsy with intraepidermal nerve fiber density (IENFD) measurement, as this patient's symptoms—hot, burning, red feet at night—are classic for SFN, which can occur independently of psoriasis or its treatments.

The negative rheumatology workup has appropriately excluded inflammatory arthritis, but the 2-year duration of neuropathic symptoms despite gabapentin treatment suggests an undiagnosed underlying cause that requires specific investigation.

Differential Diagnosis to Investigate

Small Fiber Neuropathy Workup

• Obtain skin punch biopsy (typically from distal leg and proximal thigh) to measure IENFD—this is the gold standard diagnostic test for SFN when standard nerve conduction studies are normal
• Screen for metabolic causes:
  • Hemoglobin A1C and fasting glucose (diabetes/prediabetes)
  • Vitamin B12, folate, methylmalonic acid
  • Thyroid function tests
  • Complete metabolic panel including liver and kidney function
• Screen for autoimmune causes:
  • Antinuclear antibody (ANA)
  • Sjögren's antibodies (SS-A, SS-B)
  • Celiac panel (tissue transglutaminase antibodies)
• Consider autonomic testing if patient reports orthostatic symptoms, gastrointestinal dysmotility, or sudomotor dysfunction

Erythromelalgia Consideration

• The specific presentation of red, hot, burning feet triggered at night raises concern for erythromelalgia, which can be:
  • Primary (idiopathic or genetic)
  • Secondary to myeloproliferative disorders
• Obtain complete blood count with differential to screen for polycythemia vera or essential thrombocythemia
• Consider JAK2 mutation testing if CBC shows elevated platelets or hematocrit

Skyrizi Safety Review

The FDA label for risankizumab (Skyrizi) does not list peripheral neuropathy or burning feet as recognized adverse effects 1. The most common side effects include upper respiratory infections, headache, fatigue, and injection site reactions 1. There is no established causal relationship between risankizumab and peripheral neuropathy, making it unlikely that Skyrizi is the primary cause of this patient's symptoms.

Risankizumab has demonstrated excellent long-term safety through 6 years of continuous treatment, with low rates of treatment-emergent adverse events and adverse events leading to discontinuation 2. The drug maintains high efficacy and is well-tolerated even in patients with cardiometabolic comorbidities 3.

Medication Optimization

Current Neuropathic Pain Management

• Gabapentin appears inadequately dosed or ineffective given persistent symptoms for 2 years
• Klonopin (clonazepam) is not indicated for neuropathic pain and carries risks of dependence, cognitive impairment, and falls—consider tapering and discontinuing
• Alternative neuropathic pain agents to consider:
  • Increase gabapentin to therapeutic doses (1800-3600 mg/day in divided doses) if not already maximized
  • Switch to pregabalin 150-300 mg twice daily (often better tolerated with more predictable pharmacokinetics)
  • Add duloxetine 60 mg daily (particularly effective for painful diabetic neuropathy and has evidence in SFN)
  • Consider topical agents: capsaicin 8% patch or compounded topical amitriptyline/ketamine cream

Psoriasis Treatment Continuation

Continue risankizumab (Skyrizi) without interruption, as there is no evidence linking it to the patient's neuropathic symptoms 1, 4, 5. Risankizumab demonstrates superior efficacy compared to other biologics, with 86% of patients achieving PASI 90 at 6 years and excellent safety profiles 2. Discontinuing effective psoriasis therapy would risk disease flare without addressing the true cause of the burning feet.

Critical Pitfalls to Avoid

• Do not attribute neuropathic symptoms to psoriasis treatment without evidence—this leads to unnecessary discontinuation of effective therapy
• Do not continue benzodiazepines long-term for neuropathic pain—they lack efficacy for this indication and carry significant risks
• Do not delay metabolic screening—undiagnosed diabetes or prediabetes is a leading cause of SFN and requires immediate intervention
• Do not assume negative rheumatology workup excludes all causes—SFN and erythromelalgia require specific neurologic and hematologic evaluation

Referral Strategy

• Neurology consultation for comprehensive SFN evaluation including skin biopsy, autonomic testing, and neuropathic pain management optimization
• Hematology consultation if CBC reveals abnormalities suggesting myeloproliferative disorder
• Pain management specialist if symptoms remain refractory to first-line neuropathic agents

Expected Timeline

• Skin biopsy results typically available within 2-3 weeks
• Metabolic and autoimmune screening results within 1 week
• Medication adjustments should show benefit within 2-4 weeks if neuropathic pain agents are appropriately dosed
• If erythromelalgia is confirmed, cooling measures and aspirin (if platelet-mediated) may provide rapid symptomatic relief