Keratosis follicularis spinulosa decalvans (KFSD) is a rare X-linked hereditary disorder characterized by the triad of follicular hyperkeratosis-photophobia-alopecia. The clinical heterogeneity makes the diagnosis difficult. To investigate the clinicopathologic and trichoscopic features of KFSD and to further clarify the essential requisites for the diagnosis, we conducted a retrospective study of patients with KFSD. The clinical information, histologic features, and trichoscopic findings were evaluated. Eight patients were from seven separate families. Two females were mother and daughter from the same family and the other six patients were male and represented sporadic cases. The average age of onset of alopecia was 21.25 years. Involvement of the scalp hairs leading to progressive scarring alopecia on the midline of the scalp with variable degrees of inflammation was the pathognomonic feature. It typically began after puberty. Vellus hair-associated follicular hyperkeratosis affected all of the patients. However, photophobia was not a constant feature. Histopathologic examination revealed disorders of the hair follicle with an acute-chronic inflammatory response. Follicular changes including fused infundibulum, the protrusion of the outer root sheath into the follicular canal, and a dilatation of the follicles at the isthmus level caused by the occlusion of keratin were observed. The trichoscopic features included perifollicular scaling, tufted hairs, and loss of follicular openings. In conclusion, terminal hair involvement, either scalp hairs, eyebrows, or eyelashes, and the hyperkeratosis of the follicle of vellus hairs is the diagnostic basis of KFSD. We hypothesize that follicular changes in histopathology are the primary event that trigger variable inflammation and further follicular destruction.

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BACKGROUND: Keratosis pilaris is a common keratinization disorder of the extensor surfaces of the proximal extremities. Various treatment modalities reduce symptoms, but their efficacy is limited.
OBJECTIVE: The aim of this study is to compare the efficiency of Q-Switched Nd: YAG laser and fractional Er: YAG laser.
METHODS: The lesions in both arms were randomly divided into areas A and B. Fractional Er: YAG 2940 nm laser performed to area A 1.5 J/cm2 , spot size 7 mm, frequency 3 Hz and three passes and Q-Switched Nd: YAG 1064 nm laser performed to Area B, 4-6 J/cm2 spot size 4 mm, 8 Hz frequency, and as a single pass. Both lasers were performed in 4 sessions at 3-week intervals. The global improvement scale evaluated treatment responses in dyspigmentation and skin texture.
RESULTS: Twenty patients completed the study, and the mean age of a total of 20 patients was 22.9. There was no significant difference in dyspigmentation and skin texture with global improvement scale between Area A and Area B, respectively (p = 0.078, p = 0.638). In addition, there was no significant difference between patient satisfaction levels after treatment in Area A and Area B (p = 0.868).
CONCLUSIONS: The efficiency of the fractional Er: YAG 2940 nm laser was found equal to the Q-switched Nd: YAG 1064 nm laser. Fractional Er: YAG 2940 nm laser may be a new treatment option in the treatment of keratosis pilaris.

Keratosis pilaris (KP) associates with epidermal barrier defects in atopic dermatitis (AD) but its role in disease severity and concomitant atopic diseases seems to vary between populations. We performed a cross-sectional observational study with 502 randomly selected AD patients of a Finnish tertiary health care center. At a single clinical examination, disease severity (Rajka Langeland severity score and EASI), clinical signs and patient history were evaluated and total IgE levels and frequent filaggrin (FLG) loss-of-function mutations were investigated. There was no link with disease severity (p = 0.649, 95% CI 0.569-0.654), asthma (p = 0.230, 95% CI 0.206-0.281) or atopic sensitization (p = 0.351, 95% CI 0.309-0.392). Keratosis pilaris was significantly associated with palmar hyperlinearity (p < 0.000, 95% CI 0.000-0.006, OR 4.664, 95% CI 2.072-10.496) and the filaggrin loss-of-function mutation 2282del4 (p < 0.000, 95% CI 0.000-0.009, OR 4.917, 95%CI 1.961-12.330). The prevalence of KP in the cohort was generally low and KP seems to be infrequent in Finnish AD patients. This may be explained by the fact that the tested FLG loss-of-function mutations are rarer in the Finnish population compared for example, with central Europe or Asia. Mutations in other locations of the FLG gene or other genes of the epidermal barrier may play a more important role.

Darier disease and Hailey-Hailey disease are severe, monogenetic dermatological disorders with mutations affecting all cells, making them liable to exhibit extra-dermal symptoms. The aim of this study is to assess broad cognitive function in individuals with these diseases, using an experimental, case-control set-up comparing cognition in patients with that in healthy controls matched for age, sex and level of education. Cognition was assessed with the Cambridge Neuropsycho-logical Test Automated Battery. Patients with Darier disease (n = 29) performed significantly poorer on 5 of the 10 key cognitive measurements, while patients with Hailey-Hailey disease (n = 25) did not perform differently from controls. The main conclusion is that patients with Darier disease exhibit significant impairment in cognitive function, which reinforces the view that Darier disease should be regarded as a disorder affecting multiple organs, and should therefore be given medical consideration, and possibly treat-ment, as such.

Patients with Hailey-Hailey and Darier diseases present with disabling inflammatory lesions located in large skin folds, which are often exacerbated or induced by sweating. Quality of life is highly impaired because of pain and recurrent skin infections. An improvement in skin lesions after botulinum toxin A injections has previously been reported in some patients but no prospective interventional studies are available. The aim of this open-label, 6-month, interventional pilot study (NCT02782702) was to evaluate the effectiveness and safety of botulinum toxin A for patients with moderate to very severe skin lesions located in folds.
Thirty patients (26 Hailey-Hailey/4 Darier) were included. Botulinum toxin A proved effective within the first month in two-thirds of patients, taking all study parameters (itchiness, cutaneous pain, sweating and odour, infections, psychosocial impairment and quality of life) into account and persisted during the 6-month follow-up period. No patient was classed as a BtxA non-responder, but 11 (37%) Hailey-Hailey patients (the most severe ones), experienced a relapse during the study. No serious side effects were reported. Mild transient clear fluid discharge at the site of the injections was reported for 27% of patients.
Botulinic toxin seems to be an effective and safe treatment for Hailey-Hailey and Darier diseases. Nevertheless, it may prove insufficient for the severest of Hailey-Hailey cases and could be considered as supplementary to other conventional treatments. Further studies are required to confirm our results on larger Darier cohorts.

Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in heart disease is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum Ca2+ ATPase isoform 2 (SERCA2), which causes calcium dyshomeostasis and ER stress. We hypothesized that DD patients would have an increased risk for common heart disease. We performed a cross-sectional case-control clinical study on 25 DD patients and 25 matched controls; and a population-based cohort study on 935 subjects with DD and matched comparison subjects. Main outcomes and measures were N-terminal pro-brain natriuretic peptide, ECG and heart diagnosis (myocardial infarction, heart failure and arrythmia). DD subjects showed normal clinical heart phenotype including heart failure markers and ECG. The risk for heart failure was 1.59 (1,16-2,19) times elevated in DD subjects, while no major differences were found in myocardial infarcation or arrhythmias. Risk for heart failure when corrected for cardivascular risk factors or alcohol misuse was 1.53 (1.11-2.11) and 1.58 (1,15-2,18) respectively. Notably, heart failure occurred several years earlier in DD patients as compared to controls. We conclude that DD patients show a disease specific increased risk of heart failure which should be taken into account in patient management. The observation also strenghtens the clinical evidence on the important role of SERCA2 in heart failure pathophysiology.

BACKGROUND: Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in diabetes is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum ATPase 2 (SERCA2) calcium pump, which causes calcium dyshomeostasis and ER stress. We hypothesize that DD patients have a diabetes-like metabolic phenotype and the objective of this study was to examine the association between DD with impaired glucose tolerance and diabetes.
METHODS: Cross-sectional clinical study on 25 DD patients and 25 matched controls. Metabolic status was assessed primarily by fasting blood glucose, oral glucose tolerance test, HOMA2-%S (insulin resistence) and HOMA2-%B (beta cell function).
RESULTS: DD subjects showed normal oral glucose tolerance test and HOMA2-%S, while fasting blood glucose was lower and c-peptide as well as HOMA2-%B was higher.
CONCLUSIONS: Increased HOMA2-%B values are indicative of increased basal insulin secretion which is a type of beta cell dysfunction associated to diabetes development. These results supports a role of ER stress in diabetes pathophysiology and contribute to the understanding of DD as a multi-organ syndrome.

The aim of this study was to assess and compare the efficacy of fractional CO2 laser, Q-switched Nd:YAG laser (1064 nm), and their combined use in treatment of keratosis pilaris. The study included twenty female patients. For each patient, three areas were randomly assigned to treatment by either fractional CO2 laser (area A) or Q-switched laser (1064 nm) (area C), or both types of laser (area B). All patients were assessed by digital photography at baseline and 1 month after the last session. Assessment was done by two non-blinded and two blinded investigators (blinded investigators do not know which area is treated with which machine and non-blinded knows). Patients reported the degree of satisfaction or any adverse effects also after 1 month from the last session. The three treatment modalities led to overall improvement in the KP lesions. According to patients\' score and investigator two, area B showed statistically significant improvement compared to areas A and C (p=0.001 and p=0.039, respectively). The first blinded investigators\' assessment revealed that there was statistically significant improvement in area C compared to A and B (p = 0.023). The assessment of both investigator one and the second blinded investigator revealed that there was improvement in the three areas with no statistically significant difference between them. Both fractional CO2 and Q-switched Nd:YAG laser (1064 nm) proved to be safe and effective in the treatment of keratosis pilaris regarding not only pigmentation but also follicular prominence; their combination may have an additive effect.

Keratosis pilaris (KP) is a common follicular disorder for which various topical agents and energy-based devices have been used with some efficacy. To evaluate the efficacy of a novel 1064-nm Nd:YAG laser for the reduction of skin roughness, erythema, and hyperpigmentation in KP subjects.
Twenty-three subjects with untreated KP on the upper outer arms participated in a randomized, single-blind fashion. One arm of each subject was divided into upper and lower parts. One part was randomized to be treated with an innovative 1064-nm Nd:YAG laser, while the other part received sham irradiation. Subjects received four consecutive treatments at 4-week intervals. Antera3D was used to measure skin roughness, erythema, and hyperpigmentation at baseline and 4 weeks after the last treatment. Moreover, clinical outcomes were also evaluated by subjects\' Global Improvement Score (GIS) and subjects\' satisfaction grading scores.
Twenty-three subjects completed the study. There was statistically significant reduction of skin roughness measured by Antera3D compared with control group (P < 0.001). There were statistically significant improvements of skin roughness, erythema, hyperpigmentation, and overall appearances graded by subjects\' Global Improvement Score (P < 0.001 all). Subjects\' satisfaction scores were graded significantly better in treatment parts (P < 0.001). No adverse events including burning, bulla, erosion, post-inflammatory hyper/hypopigmentation, and scar formation developed in any subjects throughout the study period.
This innovative 1064-nm Nd:YAG laser has proved to significantly and safely reduce skin roughness in Thai KP subjects compared with control after four sessions. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.