Conference Coverage
Chronic GVHD linked to fivefold increase in squamous cell skin carcinomas
PORTLAND – Nonmelanoma skin cancers may be a higher risk with GVHD than has previously been quantified.
NEW YORK – Dermatologists have an important role to play in caring for patients with chronic graft versus host disease (GVHD), a condition whose cutaneous manifestations are many, stubborn, and often disabling.
Although a wide range of systemic therapies are available, topical and intralesional treatment with such agents as potent steroids and calcineurin inhibitors can also help with cutaneous manifestations of GVHD in some instances, said Kathryn Martires, MD, at the American Academy of Dermatology summer meeting. However, she noted, “there are no studies or series examining the use of topical steroids alone in these patients, partly speaking to the complexity of these patients and required other care, but partly also due to the lack of dermatologists’ involvement in the care of these patients on a wide scale.”
“The types of GVHD that are particularly amenable to high dose steroids are predominantly the epidermal types,” she said. These include ichthyotic and eczematous as well as lichen planus–like cutaneous GVHD. “We also use topical steroids frequently in the papulosquamous type, though this is a rare variant,” she added.
Topical steroids can be used for dermal skin changes of GVHD as well, including lichen sclerosus–like and focal morphea–like plaques, according to Dr. Martires of the department of dermatology at Stanford (Calif.) University. These lesions are often first seen in the skin folds of the neck.
Even for patients with more diffuse dermal sclerosis, topical steroids have a role in quieting specific areas where active flares are occurring, she noted. These flares can look like erythematous, scaly patches and are “particularly amenable” to spot treatment with topical steroids.
“Just like in vitiligo that’s not associated with GVHD, certainly, topical steroids have their role in treating vitiligo that’s associated with chronic GVHD,” Dr. Martires said. This scenario stands in contrast to the situation where a patient has postinflammatory hyperpigmentation, for example, further along in the course of epidermal GVHD. Steroids should be avoided in situations where there’s hyperpigmentation.
Topical steroids are not usually useful for chronic poikilodermatous GVHD, or, generally, when patients have little epidermal change and the GVHD-associated changes are mostly dermal or subcutaneous, she said.
“Intralesional steroids have their role” in GVHD, although this is another instance where there are no studies to back up their efficacy, and recommendations are based on consensus, Dr. Martires pointed out. Nodular sclerotic GVHD is a rare manifestation, with firm, keloid-like lesions. These can flatten with intralesional injections, said Dr. Martires.
Intralesional injections have also been described in the literature as a treatment for ulcerative oral GVHD, she noted. Other therapy options for oral mucosal GVHD are fluocinonide gel 0.05% or clobetasol gel 0.05%, with spot application to the lesions. When there’s more diffuse lichenoid GVHD of the mouth, dexamethasone or prednisolone oral rinses can also be used, but should be combined with nystatin to prevent thrush, she advised. Triamcinolone 0.1% can be used with topical benzocaine dental paste (Orabase).
Calcineurin inhibitors are another option for oral lesions. Patients generally have a good comfort level with starting topical calcineurin inhibitors, said Dr. Martires, because they’ve likely had exposure to the systemic formulation. Case series have reported improvement “primarily in lichenoid GVHD” with the adjunctive use of topical calcineurin inhibitors, she said. In the mouth, tacrolimus 0.1% can be put in dental paste for focal lesions, and cyclosporine and azathioprine oral solutions can also be used.
Dry mouth is common in GVHD. “Remember, in patients who have other skin symptoms like pruritus, to ask about oral sicca symptoms in order to avoid things that might exacerbate it, like antihistamines and [tricyclic antidepressants],” she added.
Genital mucosal GVHD can respond to topical steroids, with ointment as the preferred vehicle, said Dr. Martires, noting that clobetasol 0.05% ointment and fluocinolone 0.025% ointment are good options, and tacrolimus 0.1% ointment is a logical nonsteroidal topical choice for the genital mucosa.
“Intralesionals are also first-line therapy here,” and “may prevent progression and permanent scarring if initiated early,” she pointed out. However, these injections are quite painful, so “patients have to be quite motivated” to be on board with this line of therapy, she said, adding that numbing prior to injections can help with pain.
Genital discomfort in women may not all be GVHD-related. “Remember, in patients who have undergone several cycles of chemotherapy prior to transplant, that they often have been experiencing menopausal symptoms, sometimes for years, so estrogen cream can sometimes go a long way,” said Dr. Martires, adding, “Certainly, a reminder about lubrication during intercourse is appropriate.”
Also, she said, dermatologists can help patients understand how important it is to be vigilant in preserving skin integrity by, for example, keeping skin well moisturized, avoiding aggressive nail care, and wearing gloves for wet work.
Dr. Martires reported no relevant financial relationships.
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