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Chapter 125: Cutaneous Graft-Versus-Host Disease

Owen R. Dean; Edward W. Cowen

CUTANEOUS GRAFT-VERSUS-HOST DISEASE

Therapeutic Approach

Graft-versus-host disease (GVHD) is a multisystem consequence of allogenic hematopoietic stem cell transplantation. Acute cutaneous GVHD typically presents 2-4 weeks following transplant and ranges from an asymptomatic exanthem to widespread necrolysis. Chronic GVHD is a polymorphous disease and can be divided into nonsclerotic features—papulosquamous, poikiloderma, lichen planus, lichen sclerosus-like—and sclerotic features—resembling morphea, scleroderma, or eosinophilic fasciitis. Therapy should consider skin disease subtype and other organ activity (eg, ocular, oral, GI, pulmonary disease). First-line treatment is typically systemic corticosteroids. Treatment for steroid-refractory disease is not standardized—only ruxolitinib, ibrutinib, and belumosudil are FDA-indicated for GVHD—and referral to clinical trial should be considered. See Table 125-1.

Table 125-1Cutaneous Graft-Versus-Host Disease Treatment Table
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Table 125-1 Cutaneous Graft-Versus-Host Disease Treatment Table
MEDICATION NAME INDICATIONSb MECHANISM OF ACTION DOSING ADVERSE EFFECTS SUGGESTED MONITORING LEVEL OF EVIDENCE (REFERENCE)
Topical Therapy
Corticosteroids A, EC Anti-inflammatory Mid- to high-potency; low-potency for face, axilla, and long-term use, BID Skin atrophy, striae None IV1,2
Calcineurin inhibitors EC, ScC Anti-inflammatory Tacrolimus 0.03%, 0.1%; pimecrolimus 1% BID Burning sensation—transient None IIA3,4
Calcipotriene A, EC Vitamin D analogues 0.005% BID Skin irritation None III5,6
Tretinoin EC Immuno­modulator 0.05% QD. Np preferred vehicle Hypo/hyperpigmentation, sun sensitivity None III7
Ruxolitinibc EC, ScC JAK1/2 inhibitor 1.5% BID Erythema, transient acne Baseline CBC, Plt count, LFTs III8-10
Antipruritics A, EC Anesthetic, antihistamine, emollient Pramoxine, diphenhydramine, menthol-based creams None None IV1
Systemic Therapyd
Corticosteroids A, EC, ScC Anti-inflammatory A: methylprednisone 1-2 mg/kg; C: prednisone 0.5-1 mg/kg Osteoporosis, bone necrosis, diabetes Routine lipid panel, blood glucose, bone mineral density IIB2,11-14
Calcineurin inhibitors A, EC, ScC Anti-inflammatory Cyclosporine (CsA): 6.25 mg/kg BID orally, trough levels >200 mg/L; tacrolimus: 0.03 mg/kg/d IV or 0.12 mg/kg/d orally, target levels 5-10 ng/mL Infection, hypertension, renal insufficiency, hepatotoxicity, neurotoxicity, TMA Trough levels, CMP, blood pressure, lipid profile, blood glucose 3× weekly for the first month

CsA: IB15

Tacrolimus: III16,17
mTOR inhibitors A, EC, ScC Anti-inflammatory Rapamycin: loading dose 10 or 15 mg/m2, then 4-5 mg/m2 daily; reduce if levels >20 ng/mL, target levels 3-12 ng/mL Infections, TMA, cytopenias, increased blood triglycerides, lipids Weekly to monthly serum trough levels, CBC, LFTs, lipids, creatinine, urine protein III18,19
Rituximab A, EC, ScC Monoclonal antibody against CD20 antigen 375 mg/m2/wk for 4 consecutive weeks Cytopenias, hepatitis B reactivation, infections, renal toxicity CBC, Plt count, electrolytes, renal function, blood pressure every 2-4 mo; baseline HBV screening

A: III20

EC/ScC: IIB21,22
Ruxolitiniba A, ScC JAK1/2 inhibitor 5-10 mg BID Cytopenias, viral infection CBC, Plt count every 2-4 wk IB23-25
Ibrutiniba EC, ScC BTK inhibitor 420 mg once daily Cytopenias, bruising, stomatitis, diarrhea, nausea, hemorrhage, pneumonia (>20%), atrial fibrillation CBC monthly IB26...

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