Prurigo Nodularis (Investigational Adjunct)

Investigational adjunct for refractory prurigo nodularis; potent topical/intralesional steroids, gabapentinoids, and dupilumab (FDA-approved 2022) remain evidence-based.

Tier C — InvestigationalInvestigationalLast updated: 2026-05-26 · Reviewed by ASH Editorial Board

Patient Summary

Is this FDA-cleared for this use?: Not FDA-cleared for prurigo nodularis. FDA cleared medicinal leeches only for venous congestion in microsurgical reconstruction (K040187, June 2004). Use here is Tier C investigational.
What evidence exists?: Tier C (investigational). No controlled trials. Evidence-based first-line management is high-potency topical corticosteroid under occlusion, intralesional triamcinolone, topical tacrolimus or cryotherapy for limited disease, and for moderate-to-severe disease dupilumab (FDA-approved 2022 for prurigo nodularis), nemolizumab, or other systemic options including gabapentinoids and antidepressants for itch control.
Main risks: Bleeding from each bite site for 6 to 10 hours after the leech detaches
Iron-deficiency anemia from cumulative blood loss across multiple sessions
Aeromonas hydrophila wound infection from leech gut bacteria (uncommon outside reconstructive surgery, but possible)
Allergic reaction to leech saliva (rare; ranges from local itching to anaphylaxis)
Permanent Y-shaped bite-mark scars or hyperpigmentation at attachment sites
Local pain, bruising, swelling, or itching for 1 to 3 days after each session
Itch worsening immediately after leech sessions
Aggravation of nodules by additional cutaneous inflammation
Triggering scratch-itch cycle relapse
Who should not consider this: Patients eligible for dupilumab who have not been offered it (FDA-approved for moderate-to-severe PN)
Patients without workup for underlying itch causes (renal disease, cholestasis, hematologic, atopic dermatitis)
Patients with poorly controlled atopic dermatitis or psoriasis driving the itch
Anyone on blood thinners such as warfarin, apixaban, rivaroxaban, dabigatran, heparin, or daily aspirin used for medical reasons
People with hemophilia or any other inherited bleeding disorder
Patients with severe anemia (hemoglobin under 10 g/dL)
People with an active infection at the planned application site
What to ask your clinician: Has dupilumab — the FDA-approved biologic for PN — been considered or tried?
Have I been worked up for systemic causes of itch (renal, liver, hematologic)?
Have I tried gabapentin or an antidepressant for the itch component?
What is the published evidence base for leeches in PN?
What is the risk that bites worsen itch or trigger more nodule formation?
How will treatment success be measured?
When to seek urgent care: Bleeding from a bite site that soaks through more than one dressing per hour
Bleeding that continues more than 24 hours after the leech detached
Spreading redness, warmth, swelling, pus, or red streaks around any bite site
Fever over 38.0 C / 100.4 F, chills, or feeling suddenly unwell after a session
Hives, facial or tongue swelling, throat tightness, or any difficulty breathing
Sudden weakness, dizziness, fast heart rate, or fainting (possible severe blood loss)
Spreading infection at nodule sites with fever
Sudden uncontrolled itch with new systemic symptoms (jaundice, weight loss, lymphadenopathy)

What this does NOT mean

It does not mean leech therapy is FDA-cleared for prurigo nodularis — the only FDA clearance is venous congestion in microsurgical reconstruction (K040187, June 2004).
It does not replace dupilumab, which IS FDA-approved for moderate-to-severe PN.
It does not address the scratch-itch cycle that perpetuates nodules.
It does not exclude or treat systemic causes of itch.
It does not have controlled-trial evidence in PN.

Safety cross-references

Clinical Profile

Category: dermatological
ICD-10: L28.1, L29.8
Safety tier: medium

Evidence Summary

Prurigo nodularis is a chronic inflammatory dermatosis with hyperkeratotic, intensely pruritic nodules in the itch-scratch cycle. Evidence-based management includes potent topical or intralesional corticosteroids, calcineurin inhibitors, topical capsaicin, oral gabapentinoids or low-dose naltrexone for itch, phototherapy, and dupilumab (FDA-approved for moderate-to-severe prurigo nodularis in 2022). Nemolizumab (anti-IL-31RA) has positive phase III data. No published controlled trials of hirudotherapy exist for prurigo nodularis. Anecdotal reports describe perilesional application, though the underlying pathophysiology is neuroimmune and unlikely to respond to local mechanical-pharmacologic effects. Lesions are often on extensor surfaces in elderly patients with comorbid systemic disease.

Treatment specifics

How many leeches, where they are placed, how long a session lasts, and whether to repeat are clinical decisions made by a qualified provider under institutional protocol — not something to self-administer. Discuss the specifics with a clinician experienced in medicinal leech therapy. (Clinicians: switch the audience selector in the top bar to “Clinician” to view protocol detail.)

Contraindications

Active anticoagulant therapy (warfarin INR >2.0, DOACs, heparin)
Hemophilia or other bleeding disorder
Severe anemia (Hb <10 g/dL)
Active bacteremia or sepsis
Known hypersensitivity to leech salivary proteins
Pregnancy (relative — first/third trimester)
Immunocompromised state with severe neutropenia
Excoriated, infected, or actively oozing nodule
Underlying systemic itch cause not worked up (uremia, cholestasis, lymphoma)
Dupilumab eligible and accessible (use evidence-based therapy)
HIV or other immunocompromise where superinfection risk is high

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