Challenges of COVID‐19 pandemic for dermatology
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a new coronavirus responsible for the pandemic named coronavirus disease 2019 (COVID‐19). The disease causes SARS with a significant morbidity and mortality. We provide a review with a focus on COVID‐19 in dermatology. We discuss triage of suspected infectious patients, protection of medical doctors and nurses. We discuss the available data on cutaneous symptoms, although disease‐specific symptoms have yet not been observed. COVID‐19 is a challenge for the treatment of dermatologic patients, either with severe inflammatory disorders or with skin cancer. The consequences for systemic treatment are obvious but it will be most important to collect the clinical data for a better decision process. Last but not least, education in dermatology for students will not be temporarily possible in the classical settings. COVID‐19, although not a skin disease, by itself has an immense impact on dermatology.
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a new coronavirus responsible for the pandemic named coronavirus disease 2019 (COVID‐19). The disease causes SARS with a significant morbidity and mortality. We provide a review with a focus on COVID‐19 in dermatology. We discuss triage of suspected infectious patients, protection of medical doctors and nurses. We discuss the available data on cutaneous symptoms, although disease‐specific symptoms have yet not been observed. COVID‐19 is a challenge for the treatment of dermatologic patients, either with severe inflammatory disorders or with skin cancer. The consequences for systemic treatment are obvious but it will be most important to collect the clinical data for a better decision process. Last but not least, education in dermatology for students will not be temporarily possible in the classical settings. COVID‐19, although not a skin disease, by itself has an immense impact on dermatology.
Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data
Summary
Background
Relamorelin, a pentapeptide ghrelin receptor agonist, accelerated gastric emptying significantly and improved symptoms in adults with diabetic gastroparesis in phase 2 trials.
Aim
To assess the safety and tolerability of relamorelin across phase 2 trials.
Methods
Safety assessments in patients aged 18‐75 years (weight, adverse events [AEs] and laboratory tests) from two randomised, double‐blind phase 2 trials (NCT01571297, NCT02357420; results published previously) were reviewed descriptively. Analysis of covariance assessed treatment effect on glycated haemoglobin (HbA1c) and blood glucose post hoc. Phase 2a and 2b trial durations were, respectively, 4 weeks (relamorelin 10 µg once or twice daily [b.d.] or placebo b.d.) and 12 weeks (relamorelin 10, 30 or 100 µg or placebo b.d.) with 1‐ and 2‐week, single‐blind placebo run‐ins.
Results
Among 204 phase 2a and 393 phase 2b patients, respectively, 67% and 62% were female, and 88% and 89% had type 2 diabetes. Proportions of patients reporting serious AEs were similar across treatment groups, as were those with ≥1 treatment‐emergent AE (TEAE). TEAE‐related discontinuations were proportionally higher in relamorelin groups than placebo. Of 12 serious TEAEs in phase 2a, none occurred in >1 patient. In phase 2b, five serious TEAEs were reported in >1 patient, and one (100 µg) died (urosepsis), all unrelated to relamorelin. In phase 2b, increased HbA1c and fasting blood glucose levels were dose‐related (P
Infantile hypertrophic pyloric stenosis in patients with esophageal atresia
Abstract
Background
Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive of a relationship. A shared etiology makes sense from a developmental perspective as both affected structures are foregut derived. A genetic component has been described for both conditions as single entities and EA and IHPS are variable components in several monogenetic syndromes. We hypothesized that defects disturbing foregut morphogenesis are responsible for this combination of malformations.
Methods
We investigated the genetic variation of 15 patients with both EA and IHPS with unaffected parents using exome sequencing and SNP array‐based genotyping, and compared the results to mouse transcriptome data of the developing foregut.
Results
We did not identify putatively deleterious de novo mutations or recessive variants. However, we detected rare inherited variants in EA or IHPS disease genes or in genes important in foregut morphogenesis, expressed at the proper developmental time‐points. Two pathways were significantly enriched (p
Long‐term results of the treatment of primary hyperhidrosis with oxybutynin: follow‐up of 1,658 cases
Abstract
Background
Hyperhidrosis (HH) is characterized by exaggerated sweating in a specific region due to hyperfunction of the sweat glands. In the late 2000s, we started treating patients with an anticholinergic, oxybutynin, that was not being used until then.
Objectives
To present, after 12 years of utilizing this medication in our service, the substantial experience obtained with the use of oxybutynin as an initial treatment of HH in a large series of 1,658 patients.
Methods
We analyzed 1,658 patients treated with oxybutynin for HH from May 2006 to June 2018. The patients were divided into four groups according to the main site of HH: the plantar group, the axillary group, the facial group, and the palmar group. To measure the degree of satisfaction, a quality of life (QoL) questionnaire was used.
Results
Pre‐treatment QoL was poor or very poor in more than 94% of the cases, and the palmar group had the worst quality of life. After treatment, we observed an improvement in the quality of life in 77% of patients. More than 70% of the patients in all groups present moderate or optimal subjective clinical improvement in sweating after treatment. The group with the best result was the facial group. Intense dry mouth was reported in 24.9% of all patients in all groups.
Conclusions
This study included a large number of patients followed for a long period and demonstrated the good effectiveness of treatment with oxybutynin for hyperhidrosis in the main sites of sweating.
A case of Exemestane induced pseudocellulitis
Botulinum toxin type A in chronic non‐dyshidrotic palmar eczema: A side‐by‐side comparative study
Abstract
New indications are being reported for intradermal botulinum toxin type A (BTX‐A) owing to its anti‐inflammatory and antipruritic actions. Its successful use for dyshidrotic hand eczema and lichen simplex has been reported in a few cases, while its utility in dry palmar eczema not associated with hyperhidrosis has not yet been investigated. The aim of this study was the assessment of the additive efficacy and tolerability of BTX‐A in chronic dry palmar eczema. This prospective non‐randomized side‐by‐side comparative study included 30 cases of chronic bilateral dry palmar eczema with no associated hyperhidrosis. Combined emollients and topical mid‐potency steroid on one side were compared with an additive 100 units of intradermal BTX‐A on the other side for efficacy and tolerability using both patient‐ and physician‐oriented scores over a period of 6 months. Timing and extent of improvement and relapse were recorded on both sides, together with the frequency of development of side‐effects. Both lines were effective and well tolerated, with significantly greater reduction of symptom and sign scores and higher overall patient satisfaction on the side receiving BTX‐A, an effect which lasted for a significantly longer duration on this side (4 months) as compared with the other side (1 month). In conclusion, intradermal BTX‐A at a dose of 100 units/palm is beneficial and well tolerated in chronic dry palmar eczema. Compared with topical steroid and emollients alone, its addition yielded superior efficacy that was longer lasting and more satisfactory to the patients, while exerting a steroid‐sparing effect.
New indications are being reported for intradermal botulinum toxin type A (BTX‐A) owing to its anti‐inflammatory and antipruritic actions. Its successful use for dyshidrotic hand eczema and lichen simplex has been reported in a few cases, while its utility in dry palmar eczema not associated with hyperhidrosis has not yet been investigated. The aim of this study was the assessment of the additive efficacy and tolerability of BTX‐A in chronic dry palmar eczema. This prospective non‐randomized side‐by‐side comparative study included 30 cases of chronic bilateral dry palmar eczema with no associated hyperhidrosis. Combined emollients and topical mid‐potency steroid on one side were compared with an additive 100 units of intradermal BTX‐A on the other side for efficacy and tolerability using both patient‐ and physician‐oriented scores over a period of 6 months. Timing and extent of improvement and relapse were recorded on both sides, together with the frequency of development of side‐effects. Both lines were effective and well tolerated, with significantly greater reduction of symptom and sign scores and higher overall patient satisfaction on the side receiving BTX‐A, an effect which lasted for a significantly longer duration on this side (4 months) as compared with the other side (1 month). In conclusion, intradermal BTX‐A at a dose of 100 units/palm is beneficial and well tolerated in chronic dry palmar eczema. Compared with topical steroid and emollients alone, its addition yielded superior efficacy that was longer lasting and more satisfactory to the patients, while exerting a steroid‐sparing effect.
Paravertebral extramedullary haemopoiesis in a patient with pachydermoperiostosis
New‐generation, non‐SSRI antidepressants: Drug‐drug interactions and therapeutic drug monitoring. Part 2: NaSSAs, NRIs, SNDRIs, MASSAs, NDRIs, and others
Abstract
After the development of “classical” tricyclic antidepressants and monoamine oxidase inhibitors, numerous other classes of antidepressant drugs have been introduced onto the market. The selective serotonin reuptake inhibitor class is the best‐known one, but many others exist, usually identified by their mechanism of activity. In this second part of the review, focused on new‐generation antidepressants not included among selective serotonin reuptake inhibitors, the following classes are considered: noradrenergic and selective serotonergic antidepressants; norepinephrine reuptake inhibitors; serotonin, norepinephrine and dopamine reuptake inhibitors; melatonergic agonists and selective serotonergic antagonists; norepinephrine and dopamine reuptake inhibitors; and so forth. These different mechanisms underlie tolerability and safety profiles that can be very different among the classes, with each one providing significant advantages and disadvantages in comparison with others. The main characteristics of the following antidepressants are described: mianserin, mirtazapine, setiptiline, reboxetine, viloxazine, teniloxazine, atomoxetine, nefazodone, agomelatine, bupropion, esketamine, and tianeptine. The paper is focused on their metabolism and interactions, but also includes brief notes on analytical methods useful for their therapeutic drug monitoring.
After the development of “classical” tricyclic antidepressants and monoamine oxidase inhibitors, numerous other classes of antidepressant drugs have been introduced onto the market. The selective serotonin reuptake inhibitor class is the best‐known one, but many others exist, usually identified by their mechanism of activity. In this second part of the review, focused on new‐generation antidepressants not included among selective serotonin reuptake inhibitors, the following classes are considered: noradrenergic and selective serotonergic antidepressants; norepinephrine reuptake inhibitors; serotonin, norepinephrine and dopamine reuptake inhibitors; melatonergic agonists and selective serotonergic antagonists; norepinephrine and dopamine reuptake inhibitors; and so forth. These different mechanisms underlie tolerability and safety profiles that can be very different among the classes, with each one providing significant advantages and disadvantages in comparison with others. The main characteristics of the following antidepressants are described: mianserin, mirtazapine, setiptiline, reboxetine, viloxazine, teniloxazine, atomoxetine, nefazodone, agomelatine, bupropion, esketamine, and tianeptine. The paper is focused on their metabolism and interactions, but also includes brief notes on analytical methods useful for their therapeutic drug monitoring.
The effect of freeze‐thaw cycles on determination of immunoreactive plasma adrenocorticotrophic hormone concentrations in horses
Abstract
Background
Determination of plasma adrenocotrophic hormone (ACTH) concentration (endogenous or thyrotropin‐releasing hormone [TRH] stimulation test) is the most commonly used diagnostic test for pituitary pars intermedia dysfunction (PPID) in horses. Because ACTH is unstable, samples often are frozen to be shipped to laboratories or to allow for batch analysis of research samples. However, the effect of multiple freeze‐thaw cycles on equine ACTH is unknown.
Objective
To determine the effects of multiple freeze‐thaw cycles on immunoreactive ACTH concentration.
Animals
Twenty‐eight horses ranging from 10 to 27 years of age were used.
Methods
Prospective study. Horses were divided into 4 groups: group 1, PPID‐negative, without TRH stimulation; group 2, PPID‐negative, with TRH stimulation; group 3, PPID‐positive, without TRH stimulation; and group 4, PPID‐positive, with TRH stimulation. Whole blood was collected from each horse at baseline or 30 minutes after TRH stimulation. Immunoreactive plasma ACTH concentration was determined using a chemiluminescence assay. Plasma samples then were frozen at −80°C >24 hours, thawed at 4°C and reanalyzed for 5 freeze‐thaw cycles. Changes in plasma ACTH concentration were analyzed using a linear mixed‐effect model.
Results
Significant effects of freeze‐thaw cycles (P = .001) and PPID status (P = .04) on plasma ACTH concentration were observed, but no significant effect of TRH stimulation was identified.
Conclusions and Clinical Importance
The plasma ACTH concentration is altered by freeze‐thaw cycles, and the effect is observed sooner in horses with PPID. To diagnose PPID, multiple freeze‐thaw cycles should be avoided when measuring plasma ACTH concentration.