What's hot?
What's hot
August 27, 2019
In this monthly column, members of Dermatology World's Editorial Advisory Workgroup identify exciting news from across the specialty.
Bryan Carroll, MD, PhD
Identifying the origin of head and neck squamous cell carcinoma of an unknown primary can inform prognosis and direct multidisciplinary treatment. Histopathologic examination of poorly differentiated squamous cell carcinoma has limited power to differentiate cutaneous and mucosal origins. While overexpression of p16 can identify a subset of mucosal squamous cell carcinoma, p16-negative tumors can be mucosal or cutaneous. The high somatic mutation burden of cutaneous squamous cell carcinoma has inhibited the identification of signature genes for staging. Fortunately, this characteristic high burden of somatic mutations has a strong association with ultraviolet light damage. This feature of UV-specific C->T mutations may provide a highly specific tool for differentiating p16-negative tumors into cutaneous or mucosal origins.
A recent study from Australia has found UV-specific C->T mutations in 15 cutaneous squamous cell carcinoma metastasis of the head and neck (J Invest Dermatol. 2019;139: 1449-58). Whole genome sequencing identified C->T transitions in a mean of 82.5% of all identified somatic mutations. Concurrently, a case report applied a similar strategy of mapping UV-specific C->T mutations in a 62-year-old with 10 pathologically enlarged lymph nodes of the left neck (Head & Neck. 2019;41: E82-E85). In this case, a simpler screening of approximately 500 cancer genes identified a predominance of C->T mutations. The signature mutations of UV damage offer a promising tool for the clinical challenge of diagnosing head and neck metastases of an unknown primary.
Harry Dao Jr., MD
Though frequently ordered in the work-up of dermatomyositis (DM), the actual clinical significance of the ANA status is debatable. Studies with small sample sizes have complicated the literature with conflicting results. The authors of a recent study sought to better understand clinical implications of the ANA status in patients with adult-onset DM (J Am Acad Dermatol. 2019;80(5): 1364-70). They performed a retrospective cohort study of patients diagnosed with DM from 1996 to 2012 at the Mayo Clinic campuses. Exclusion factors were age younger than 18, lack of a clinical presentation or skin biopsy result consistent with DM, less than three years of follow-up, or lack of ANA status obtained by ELISA.
In general, ANA testing can be positive in over half of patients with DM. In this study, out of 231 patients, 140 (61%) were ANA+, and 91 (39%) were ANA-. ANA- patients had a higher frequency of dysphagia and heliotrope rash, and there were no other statistically significant differences in signs and symptoms based on ANA status, including muscle involvement. Fifty-four patients (23%) had a malignancy diagnosed within three years of their DM diagnosis. The most common malignancy types were ovarian (29% females), breast (27% females), and lung (11% either sex). Take home point: In patients with adult-onset DM, ANA negativity was strongly associated with a higher likelihood of malignancy within three years of diagnosis (43% vs 11%). This study has potentially identified a high-risk subgroup that should be closely followed, though we must still do our due diligence in malignancy screening in all cases. I am excited to review my clinical records now to see if my cases of DM follow this finding, but this report is a humbling reminder of how little we know about the complex pathophysiology of this disease!
Seth Matarasso, MD
The therapeutic use of neurotoxins in medicine dates back over a quarter of a century. However, it was not until 2002 that the first toxin, onabotulinumtoxinA, received FDA approval for the “temporary treatment of glabellar lines in adults.” Since then, there has been robust scientific scrutiny of its mechanism of action with a consequent expanding list of therapeutic and aesthetic indications. Ironically, what was once labeled the most poisonous “poison” has received unprecedented acceptance by patients and physicians alike. Currently, treatment with botulinum toxin type A has become the leading nonsurgical cosmetic procedure in the United States. A recent survey by the ASDS shows that the use of botulinum toxin type A by dermatologists has exceeded over 2 million people per year. This created an interest by manufacturers to develop new toxins and share in the multibillion-dollar industry (Allergan generated a $3.58 billion revenue in 2018). The other type A toxins produced by Clostridium botulinum include abobotulinumtoxinA and incobotulinumtoxinA, which have subsequently received FDA approval for specific facial rhytides.
In 2019, Jeuveau received FDA approval solely for the treatment of glabellar lines. Its approval was supported by clinical data from two U.S. Phase III randomized, multi-center, double-blind, placebo-controlled trials that enrolled 2,100 patients (Dermatol Surg. doi: 10.1097/DSS.0000000000001903). Like onabotulinumtoxinA, this biosimilar drug is also a 900 kDa toxin and each 100 unit vial is reconstituted with 2.5 mL of 0.9 non-preserved sterile saline. The intramuscular injection pattern and the 20 unit dose (5 injections 4 units/0.1mL) showed a similar onset of action, percentage of responders, duration (150 days), and adverse events profile. The effectiveness of prabotulinumtoinA and noninferiority to onabotulinumtoxinA make it a safe and viable option for the reduction of facial lines.
As Paracelsus stated, “Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy.”
Christen Mowad, MD
Does adult-onset atopic dermatitis exist? There is an ongoing debate in the literature as to whether adult-onset atopic dermatitis is a real disease, or if it is adult-recurrent atopic dermatitis in those who may not recall their earlier symptoms. A recent study conducted a systematic review and meta-analysis of the prevalence and phenotypes of adult-onset atopic dermatitis (JAAD. 2019;80(6): 1526-1532). They found that 1 in 4 adults with atopic disease report adult-onset over the age of 16. They also found that adult-onset atopic dermatitis was associated with different morphologic characteristics than child-onset atopic dermatitis. They found that childhood-onset atopic dermatitis was found to have more facial dermatitis, eyelid dermatitis, cheilitis, pruritus, sweating, and Dennie-Morgan lines. Adult-onset atopic dermatitis was associated with more foot dermatitis and less flexural disease. The authors point out that biopsy and patch testing may be helpful tools used to rule out other conditions. However, in some of the studies that were reviewed, even positive and relevant patch testing with allergen avoidance did not always resolve the atopic dermatitis. The authors comment that more studies need to be done to further determine incidence, pathomechanisms, triggers, and phenotypic characteristics of adult-onset atopic dermatitis. They go on to point out that considering the possibility of adult-onset atopic disease — whether it is an adult-recurrent or true adult-onset disease — is important so that providers also consider the use of appropriate atopic disease therapy.
