Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus:important lessons from longitudinal follow-up

OBJECTIVES: To observe if capillary patterns in childhood-onset SLE (cSLE) change over time and find associations between a capillary scleroderma pattern with disease activity, damage or scleroderma-like features. METHODS: Clinical and (yearly) capillaroscopy data from a longitudinal cohort of patients with cSLE (minimum of four Systemic Lupus International Collaborating Clinics (SLICC) criteria, onset <18 years) were analysed. Disease activity was measured by Systemic Lupus Erythematosus Activity Index (SLEDAI) and disease damage by SLICC Damage Index. A scleroderma pattern was defined according to the ‘fast track algorithm’ from the European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases. An abnormal capillary pattern, not matching a scleroderma pattern, was defined as ‘microangiopathy’. RESULTS: Our cohort consisted of 53 patients with cSLE with a median disease onset of 14 years (IQR 12.5–15.5 years), median SLEDAI score at diagnosis was 11 (IQR 8–16), median SLEDAI at follow-up was 2 (IQR 1–6). A scleroderma pattern (ever) was seen in 18.9%, while only 13.2% of patients had a normal capillary pattern. Thirty-three patients had follow-up capillaroscopy of which 21.2% showed changes in type of capillary pattern over time. Type of capillary pattern was not associated with disease activity. Raynaud’s phenomenon (ever) was equally distributed among patients with different capillaroscopy patterns (p=0.26). Anti-ribonucleoprotein antibodies (ever) were significantly more detected (Χ(2), p=0.016) in the scleroderma pattern subgroup (n=7 of 10, 70%). Already 5 years after disease onset, more than 50% of patients with a scleroderma pattern had SLE-related disease damage (HR 4.5, 95% CI 1.1 to 18.8, p=0.034), but they did not develop clinical features of systemic sclerosis at follow-up. Number of detected fingers with a scleroderma pattern was similar between cSLE, juvenile systemic sclerosis and juvenile undifferentiated connective tissue disease. CONCLUSION: This longitudinal study shows that the majority of capillary patterns in cSLE are abnormal and they can change over time. Irrespective of disease activity, a capillary scleroderma pattern in cSLE may be associated with higher risk of SLE-related disease damage

Comparison of real-world treatment outcomes of systemic immunomodulating therapy in atopic dermatitis patients with dark and light skin types

Background Few data exist on differences in treatment effectiveness and safety in atopic dermatitis patients of different skin types. Objective To investigate treatment outcomes of dupilumab, methotrexate, and ciclosporin, and morphological phenotypes in atopic dermatitis patients, stratified by Fitzpatrick skin type. Methods In an observational prospective cohort study, pooling data from the Dutch TREAT (TREatment of ATopic eczema) NL (treatregister.nl) and UK-Irish A-STAR (Atopic eczema Systemic TherApy Register; astar-register.org) registries, data on morphological phenotypes and treatment outcomes were investigated. Results A total of 235 patients were included (light skin types [LST]: Fitzpatrick skin type 1-3, n = 156 [Ethnicity, White: 94.2%]; dark skin types [DST]: skin type 4-6, n = 68 [Black African/Afro-Caribbean: 25%, South-Asian: 26.5%, and Hispanics: 0%]). DST were younger (19.5 vs 29.0 years; P .05). Limitations Unblinded, non-randomized. Conclusion Atopic dermatitis differs in several characteristics between LST and DST. Skin type may influence treatment effectiveness of dupilumab

Confocal histopathology of irritant contact dermatitis in vivo and the impact of skin color (black vs white)

BACKGROUND: The pathogenesis of irritant contact dermatitis and its modulation according to skin color is not well understood. Reflectance confocal microscopy (RCM) enables high-resolution, real-time, in-vivo imaging of human skin. OBJECTIVE: The goal of our study was to use RCM to determine whether susceptibility to irritant contact dermatitis differs between black and white skin. METHODS: Participants were placed in groups on the basis of skin color and the volar aspects of their forearms exposed to 1% and 4% sodium lauryl sulfate using Finn Chambers (Allerderm Laboratories Inc, Petaluma, Calif). They were evaluated at 6, 24, and 48 hours by RCM, transepidermal water loss, laser Doppler velocimetry, and routine histology. RESULTS: Participants with white skin had more severe clinical reactions than those with black skin. RCM revealed microscopic changes even without clinical evidence of irritation. Confocal features included parakeratosis, spongiosis, perivascular inflammatory infiltrate, and microvesicle formation, and these features were confirmed by routine histology. Also, participants with white skin had greater mean increases in transepidermal water loss after exposure to 4% sodium lauryl sulfate than did participants with black skin. CONCLUSION: In-vivo RCM can track early pathophysiologic events revealing differences between black and white skin during the development of irritant contact dermatitis, and may support the theory that those with black skin are more resistant to irritant

Topical application of a protein kinase C inhibitor reduces skin and hair pigmentation

To determine whether inhibition of PKC-beta activity decreases pigmentation, paired cultures of primary human melanocytes were first pretreated with bisindolylmaleimide (Bis), a selective PKC inhibitor, or vehicle alone for 30 min, and then treated with TPA for an additional 90 min to activate PKC in the presence of Bis. Bis blocked the expected induction of tyrosinase activity by activation of PKC. Addition of a peptide corresponding to amino acids 501-511 of tyrosinase containing its PKC-beta phosphorylation site, a presumptive PKC-beta pseudosubstrate, gave similar results. To determine whether Bis reduces pigmentation in vivo, the backs of four shaved and depilated pigmented guinea pigs were UV irradiated with a solar simulator for 2 wk excluding weekends. Compared to vehicle alone, Bis (300 microM), applied twice daily to paired sites for various periods encompassing the irradiation period, decreased tanning. Bis also, although less strikingly, reduced basal epidermal melanin when topically applied twice daily, 5 d per wk, for 3 wk to shaved and depilated unirradiated skin. Moreover, topical application of Bis (100 microM) once daily for 9 d to the freshly depilated backs of 8-wk-old mice markedly lightened the color of regrowing hair. These results demonstrate that inhibiting PKC activity in vivo selectively blocks tanning and reduces basal pigmentation in the epidermis and in anagen hair shaft

Orally administered Polypodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin

BACKGROUND: The use of psoralen-UVA (PUVA) in patients of skin phototype I to II is limited by side effects of acute phototoxicity and possible long-term carcinogenesis. OBJECTIVE: We sought to assess oral Polypodium leucotomos (PL) extract in decreasing PUVA-induced phototoxicity of human skin on a clinical and histologic level. METHODS: A total of 10 healthy patients with skin phototypes II to III were exposed to PUVA alone (using 0.6 mg/kg oral 8-methoxypsoralen) and to PUVA with 7.5 mg/kg of oral PL. RESULTS: Clinically, phototoxicity was always lower in PL-treated skin after 48 to 72 hours (P <.005), and pigmentation was also reduced 4 months later. Histologically, PL-treated skin showed a significant numeric reduction of sunburn cells (P=.05), preservation of Langerhans cells (P <or =.01), decrease of tryptase-positive mast cell infiltration (P <.05), and decrease of vasodilation (P <or =.01). No differences were found in Ki-67+ proliferating cells. CONCLUSIONS: PL is an effective chemophotoprotector against PUVA-induced skin phototoxicity and leads to substantial benefits of skin protection against damaging effects of PUVA as evidenced by histolog

Skin barrier in atopic dermatitis

The skin represents the largest organ of the body and provides a vital interface between the body and the environment. Hereditary and acquired alterations of structural proteins and lipids of the stratum corneum and epidermal tight junctions leading to a diminished skin barrier function are major causative factors for a number of skin diseases, in particular atopic dermatitis (AD). This review summarizes current knowledge on the role of the skin barrier in AD with regard to pathogenesis and treatment, on the relationship between skin barrier abnormalities and immune aberrations, and on potential therapies aimed at repair of the skin barrier. Furthermore recent advances in the genetics of AD will be addresse

Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin

BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL). METHODS: A total of 9 healthy participants of skin types II to III were exposed to varying doses of artificial UV radiation without and after oral administration of PL (7.5 mg/kg). At 24 hours after exposure the erythema reaction was assessed and paired biopsy specimens were obtained from PL-treated and untreated skin. RESULTS: A significant decrease in erythema was found in PL-treated skin (P <.01). Histologically, PL-treated biopsy specimens showed less sunburn cells (P <.05), cyclobutane pyrimidine dimers (P <.001), proliferating epidermal cells (P <.001), and dermal mast cell infiltration (P <.05). A trend toward Langerhans cell preservation was seen. CONCLUSION: Oral administration of PL is an effective systemic chemophotoprotective agent leading to significant protection of skin against UV radiatio