– Dermatologists don’t ordinarily peruse the ophthalmology literature. So they may be unaware that the American Academy of Ophthalmology has issued revised recommendations on weight-based dosing of hydroxychloroquine in order to minimize retinopathy risk, Erik J. Stratman, MD, noted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Most dermatologists routinely dose hydroxychloroquine at 400 mg/day, regardless of body weight. The former AAO recommendation, which dates back to 2011, called for dosing at up to 6.5 mg/kg of ideal body weight or 400 mg/day, whichever is lower. However, the AAO recommendation has changed in light of a large, retrospective case-control study that suggested this practice may be overdosing thin patients – thereby exposing them to increased risk of retinal toxicity and other drug-related adverse events – while at the same time possibly underdosing some obese patients, said Dr. Stratman, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.


This was one of two dermatology practice gaps he highlighted involving suboptimal medication management, the other being most dermatologists’ failure to protect their patients’ gut when prescribing prednisone.

“I think the push over the last 5 years has been ‘protect the bones, protect the bones, protect the bones.’ We’ve done better and better about protecting the bones and getting that into our conversations with patients on prednisone. But we’re not thinking so much about the gut,” the dermatologist said.

Hydroxychloroquine dosing

The former AAO recommendation was revised in response to a retrospective case-control study of retinal toxicity rates in 2,361 patients on the drug continuously for longer than 5 years. The study demonstrated that the risk of retinopathy jumped 5.7-fold with daily consumption of hydroxychloroquine at more than 5.0 mg/kg (JAMA Ophthalmol. 2014 Dec;132[12]:1453-60).

The current AAO recommendation (Ophthalmology. 2016 Jun;123[6]:1386-94) is to dose hydroxychloroquine at a daily maximum of 5.0 mg/kg of real weight, which correlated better with retinopathy risk in the case-control study than did ideal body weight. Hydroxychloroquine doesn’t accumulate well in fat.

Until now, most dermatologists have not routinely measured patients’ body weight in the office or calculated their body mass index. But Dr. Stratman advised against reliance upon a patient’s self-reported body weight, which may diverge substantially from reality. “Get yourself a good office scale – they’re not that expensive – and use it when prescribing drugs with a tight therapeutic window,” he urged.

Another key to minimizing retinopathy risk in patients on hydroxychloroquine is to pay careful attention to how long they’ve been on the drug. As the years go by in patients being treated for cutaneous lupus or other dermatologic disorders where decades-long therapy is often a mainstay, it’s important to check with patients and make sure they’re getting annual ophthalmologic screening for irreversible retinal toxicity by both threshold visual fields and spectral domain optical coherence tomography. In the large, practice-changing retrospective study, patients on hydroxychloroquine at 4.0-5.0 mg/kg daily had a prevalence of retinopathy of less than 2% during the first 10 years of therapy, but the rate shot up to nearly 20% after 20 years of use, Dr. Stratman observed.

He highlighted as helpful an updated review of the use of hydroxychloroquine in dermatology recently published by Anthony P. Fernandez, MD, PhD, of the department of dermatology at the Cleveland Clinic (J Am Acad Dermatol. 2017 Jun;76[6]:1176-82).

Dr. Fernandez recommends following the AAO guidance to dose the drug at 5.0 mg/kg or less of actual body weight in thin or normal-weight patients; however, he departed from the ophthalmologists with regard to treatment of obese patients. Because dosing based on actual weight could potentially lead to relative overdosing in obese patients, in that growing population he recommends calculating the dose based upon 5.0 mg/kg of actual body weight, as well as the dose based on 6.5 mg/kg of ideal body weight, then prescribing the lower of the two, up to a maximum of 400 mg/day.

“The current recommendation is really about not overdosing thin patients. Basically, dosing is not so difficult for obese people because if you weigh more than 175 pounds, you’re going to get 400 mg/day,” Dr. Stratman explained.

That 400 mg/day ceiling is not cast in stone, he continued. The guideline recommends that, if a patient is a nonresponder to several months of hydroxychloroquine at 400 mg/day, it’s worthwhile to order a drug blood level. If it’s not above the efficacy threshold of more than 750 ng/mL, it’s appropriate to titrate up.

Protecting against prednisone-induced gastritis

“We underprotect the gut,” Dr. Stratman asserted.

He referred to a recent comprehensive dermatologic review of the prevention and management of glucocorticoid-related side effects, especially the part on peptic ulcer disease (J Am Acad Dermatol. 2017 Jan;76[1]:11-6). This is an issue that heretofore hadn’t been much emphasized in the dermatology literature.

“I read this and thought, ‘Gosh, I’m not really having a conversation with my patients about a review of systems for gut protection as I should. And I certainly haven’t been thinking about prescribing PPIs [proton pump inhibitors] for my patients,’” he recalled.

Dr. Stratman polled his Hawaii Dermatology Seminar audience as to who had ever prescribed a PPI. Most indicated with their electronic clickers that they had never done so.

“This is what a practice gap is,” he commented. “You read the literature and you say, ‘Oh, I guess that makes sense. Maybe I should be doing that more often, or making sure it gets done.’”

“I don’t want to come across as saying, ‘For everybody we put on prednisone we should be giving vitamin D, calcium, and a PPI.’ That’s not the message. The message is, assess your patient – or make sure your patient is being assessed – for risk of peptic ulcer disease. And if you don’t feel comfortable prescribing a PPI, please get the patient connected with their primary care provider, who should,” Dr. Stratman said.

The authors of the dermatology review made a case for screening for GI risk factors in every patient who is going to receive an oral glucocorticoid. The ones who absolutely should be prescribed a PPI unless contraindicated include patients who are taking daily aspirin or NSAIDs for an essential reason, such as cardiovascular protection or significant arthritic pain. The authors suggest consideration of a PPI in patients with other, less potent risk factors for peptic ulcer disease, including a history of ulcer disease, gastroesophageal reflux disease, Barrett’s esophagus, heavy smoking, heavy alcohol consumption, age greater than 65, and concomitant use of other medications with an associated risk of peptic ulcer disease – such as bisphosphonates, “which you may have just put them on to protect their bones,” Dr. Stratman noted.

Of course, PPIs come with side effects of their own, including increased fracture risk, Clostridium difficile infections, and rebound acid secretion.

Dr. Stratman reported having no financial conflicts regarding his presentation.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.