This month's news from across the specialty

July 1, 2021

In this monthly column, members of the DermWorld Editorial Advisory Workgroup identify exciting news from across the specialty.  

The FDA has approved the first treatment for progeria (Hutchinson-Gilford progeria syndrome). As we all know, progeria is a rare but devastating genetic syndrome that results in premature aging and death in affected patients. Disease results from abnormal accumulation of the structural protein, progerin. Although infants appear normal at birth, they quickly develop the classic clinical findings, which include a small face in relationship to head size, a small jaw, dark circles, and a beaked nose. Skin is very atrophic and appears prematurely aged. Prominent scalp veins are present. Children experience loss of body fat and body hair. Children with progeria die of atherosclerotic disease (including heart attack and stroke) at an average age of 14.5 years old. In November 2020, the FDA approved Zokinvy^® (lonafarnib), an oral medication that inhibits the formation of progerin, for children 12 months of age and older with progeria. In a study of 62 children with progeria treated with lonafarnib, lifespan was increased up to 2.5 years. Prior to this approval, the only treatment for progeria was supportive care.

Have you noticed an increasing trend that your pathology laboratory is using more immunohistochemical stains? You are not alone. The use of immunohistochemistry has been increasing with the development of newer and better stains. In dermatopathology, there are increasing trends in the use of these stains for melanocytic lesions. In an article from last year, Dinehart and colleagues studied the use of immunohistochemistry in the diagnosis of melanoma (J Cutan Pathol. 2020. 47: 446-50). In this report, they studied all biopsy-proven melanomas in an 18-month period from a single dermatology clinic. Of 356 melanomas, 228 (64%) utilized immunohistochemistry. Of these cases, 60% of melanomas from an academic institution employed stains, and 73% of those from a private laboratory. In a more recent paper from New Zealand, Chen and Hitchcock studied 1,230 cases of melanocytic lesions, benign and malignant, in their laboratory (Am J Dermatopathol. 2021. 00: 1-3). Three hundred (24.4%) of the cases utilized immunohistochemistry. This study was performed in a government-funded, not-for-profit laboratory, so there was no financial incentive for ordering more stains.

Why is there so much use of immunohistochemistry with melanocytic lesions? There are multiple explanations including: 1) In amelanotic melanocytic lesions, it is important to confirm the melanocytic lesion lineage using the stains. There is particular benefit in desmoplastic melanoma; 2) The stains assist in distinguishing between an atypical nevus, melanoma in situ, and invasive melanoma; 3) Immunohistochemical stains can assist in identifying lymphovascular invasion in malignant melanoma; 4) In some cases, stains can improve accuracy of margin assessment on melanoma excisions.

While we are seeing this increased utilization of immunohistochemistry in melanocytic lesions, I suspect there is also an increase in other types of cases such as cutaneous lymphoma. In many instances, the stains improve our diagnostic capabilities and help guide therapy, but at the same time they add to the increasing cost of health care. The development of appropriate use criteria on stain utilization is likely in our future.

Erythema multiforme (EM) is over-diagnosed. Target-like papules and plaques may be present in morbilliform drug eruptions, leading to the misdiagnosis/over-diagnosis of EM. Most published cases of drug-induced EM are actually not EM. Using the key words "erythema multiforme," a search of PubMed revealed 1,360 articles from 2010 to February 2016 (Br J Dermatol. 2016; 175(3): 650-651). In that list, 51 articles had "drug" or the name of a specific drug and "erythema multiforme" in their title. Access was obtained to 36 of these articles. Based on the photographs and clinical descriptions, and using the Bastuji-Garin clinical criteria, the reported cases were classified as (1) definite/probable EM (suggestive clinical photograph showing raised typical targets with acral distribution); (2) possible EM (atypical targets or unusual distribution); or (3) "no case" (widespread eruption, no target lesions, strong suspicion of another diagnosis). Of the 36 papers (with 37 cases), the diagnosis was considered definite/probable EM in six cases (16%), possible EM in seven cases (19%), and "no case" in 24 (65%). Alternative diagnoses in the "no case" group included three cases of Stevens-Johnson syndrome, one case of Stevens-Johnson syndrome/toxic epidermal necrolysis overlap, nine cases of maculopapular eruptions due to a drug, and five cases of allergic contact dermatitis.

Concerning drug causality of the six cases of definite/probable EM, the relationship in each case was suggested based on only the time relationship between start of the culprit drug and EM. There were no in vivo or in vitro drug tests and no author mentioned the possibility of coincidence.

This study shows that confusion on the diagnosis of EM is rampant. Disseminated maculopapular drug eruptions can present with lesions resembling targets, which can mimic EM clinically and there may sometimes be some histopathologic similarities with EM. However, one should keep in mind that EM affects well under 10% of the body surface area; the median involvement of EM is 1% of the body surface area.

Ask dermatologists about vancomycin, and they likely will associate it with “Red Man Syndrome,” a term first used in 1959 to describe histamine-mediated reactions, with prominent cutaneous manifestations, to vancomycin infusions. That term is problematic, according to authors of a Perspective in the New England Journal of Medicine (2021;14:1283-6).

Like the term “redskin” — the erstwhile mascot of the Washington Football Team — the term “Red Man” has racist connotations, the authors write, reflecting historical narratives pejorative to Native American and Indigenous people. And that’s not all. Other concerns with the term include its use of white males as a reference group; its alignment with race-based medicine; and its contribution to under-recognition of cutaneous conditions in non-white populations.

This is not merely a semantic issue. A “Red Man Syndrome” diagnosis is more likely for male patients compared with female patients, according to studies, and for white patients compared with Black patients. Physicians likely would be comfortable treating patients with a “Red Man Syndrome” diagnosis with vancomycin, after pretreatment or with a slower infusion rate. But for patients who had “Red Man Syndrome,” but were diagnosed with a less specific “allergic reaction” to vancomycin, physicians might instead choose an alternative, and likely second-line, antibiotic.

What is to be done? Jettison the term, the authors argue, as has been done with Nazi-associated medical eponyms. The authors instead advocate for use of the non-racist, more clinically useful, and more easily documented term “infusion reaction” for non-immune-mediated drug reactions such as that associated with vancomycin.

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