Chronic Actinic Dermatitis Patients Research Articles

Efficacy and safety of azathioprine versus mycophenolate mofetil in chronic actinic dermatitis in skin of color: results of a randomized controlled trial.

Chronic actinic dermatitis (CAD) is an immunologically mediated photodermatosis that has been effectively treated with azathioprine and mycophenolate mofetil (MMF) in uncontrolled studies. We conducted a prospective randomized controlled trial to compare the efficacy and safety of azathioprine and MMF in CAD treatment, aiming to address existing evidence gaps. Consecutive CAD patients were randomized into two groups: azathioprine (Group A) or MMF (Group B) for 12 weeks. Primary outcomes included Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) at baseline and Week 12. Secondary outcomes included various clinicodemographic factors predictive of treatment response, defined at least a 75% reduction in EASI score (EASI75) by Week 12. The median (IQR) percentage reduction in EASI at 12 weeks was higher in Group B than in Group A [78.3% (75.0-83.30%) vs. 68.3% (31.2-80.10%), P = 0.034]. Baseline DLQI scores indicated a moderate impact on quality of life, with significant reductions by Week 12 in both groups and no intergroup differences at baseline (P = 0.291) or Week 12 (P = 0.599). Overall, 23 patients were classified as non-responders, with more extended illness duration (P = 0.026) and outdoor occupations (P = 0.042) associated with poorer responses. Adverse effects were consistent with known profiles, with one patient discontinuing azathioprine due to hypersensitivity. Our study highlights the efficacy and safety of azathioprine and MMF in CAD treatment, with MMF showing superior outcomes. However, further research is warranted to explore emerging therapies and prognostic factors in CAD management.

Deficiency of N6-Methyladenosine Demethylase ALKBH5 Alleviates Ultraviolet B Radiation-Induced Chronic Actinic Dermatitis via Regulating Pyroptosis.

Pyroptosis is an inflammatory programmed cell death (PCD) and is reported to be associated with N6-methyladenosine (m6A) modification. This study aimed to investigate the mechanism of m6A demethylase AlkB homolog 5 (ALKBH5) in pyroptosis in the process of chronic actinic dermatitis (CAD). Changes of m6A-related genes were evaluated between CAD and normal samples using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Human keratinocytes (HaCaT cells) exposed to ultraviolet B (UVB; 10, 20, and 30mJ/cm2), followed by evaluation of cell proliferation, cell apoptosis, inflammatory cytokines (interleukin (IL)-1β, IL-18, and tumor necrosis factor (TNF-α)), and pyroptosis-related proteins (gasdermin D (GSDMD), Caspase-1, and Caspase-4). Small interfering RNA (siRNA) targeting ALKBH5 was transfected into HaCaT cells to assess the effect of si-ALKBH5 on CAD. A CAD mice model was induced after exposure to UVB (250mJ/cm2 per day) to confirm the role of ALKBH5 in CAD. AKKBH5 was highly expressed in CAD patients. UVB also promoted ALKBH5 expression, increased cell apoptosis, and induced the release of inflammatory cytokines (IL-1β, IL-18, and TNF-α) as well as pyroptosis-related proteins (GSDMD, Caspase-1, and Caspase-4). Silencing ALKBH5 repressed cell apoptosis and suppressed UVB-induced pyroptosis and inflammatory response. Meanwhile, silencing ALKBH5 attenuated UVB-induced skin damage of CAD mice, accompanied with the reduction in expression of inflammatory cytokines and pyroptosis-related proteins. This study helps to further understand the mechanism of ALKBH5 in CAD-induced pyroptosis and provides novel ideas for the research and management of CAD.

Clinical characteristics of patients with human immunodeficiency virus and immune-mediated photodermatoses: A retrospective study of 39 patients.

HIV/AIDS patients are susceptible to various infectious and inflammatory dermatoses. No systemic work has been done on HIV/AIDS patients with immune-mediated photodermatoses in China. Here, we aim to determine the clinical features of immune-mediated photodermatoses in HIV/AIDS patients. A retrospective analysis of HIV/AIDS patients with immune-mediated photodermatoses was carried out with demographic data, clinical characteristics, laboratory data, and follow-up data at the First Affiliated Hospital of Kunming Medical University between 2012 and 2019. The data were subjected to statistical analysis. A total of 39 HIV/AIDS patients with immune-mediated photodermatoses were enrolled, including 22 cases of polymorphic light eruption (PLE), 16 cases of chronic actinic dermatitis (CAD), and one actinic reticuloid. The CD4 count at the visit of the HIV-positive CAD group was lower than the PLE group (p=.049). The HIV-positive CAD group was more sensitive toward UVB than the PLE group (p=.020) and had a lower MED-UVB value (p=.044). There was no significant difference in UV tests among different categories of skin types. Immune-mediated photodermatoses are a manifestation of the advanced symptom of HIV infection, and sometimes also the presenting feature of HIV infection. Compared with HIV-positive PLE patients, CAD patients showed higher sensitivity to UVB radiation and had a lower MED-UVB value. The primary treatment for immune-mediated photodermatoses in HIV/AIDS patients is HAART and sun avoidance.

Clinical and pathological findings of chronic actinic dermatitis.

Chronic actinic dermatitis (CAD) is a recurrent photosensitive disease occurs predominantly in elderly men on sun-exposed areas, which seriously affect the patient's life quality. The etiology of CAD remains unknown. Sixty-six CAD patients, 66 atopic dermatitis (AD) patients, and 46 healthy people were enrolled into this study. Patient-level data were obtained from the electronic medical record and laboratory databases. We also obtained 29 tissue samples including 16 lichenoid lesions, 7 minimal erythematous dose (MED) analysis induced lesions, and 6 normal skin samples. Histopathologic and immunohistochemical analysis were performed. In the clinical characteristics, albumin was lower and uric acid was higher significantly in patients diagnosed as CAD. The infection rate of CAD patient after skin biopsy was considerably high (23.3%). The serum allergen test was prone to be negative in CAD patients. Lymphocytes were the dominate infiltrating cells in early and late CAD lesions, while more CD4+, CD8+, CD69+, and CD103+cells were found in the late lesions. There is no difference in CD4+/CD8+ratio and CD69+/CD103+ratio among groups. More mast cells were observed in the early-stage lesions, and more dendritic cell was observed in the late-stage lesions. CAD patients have certain oxidative stress and are prone to be infected after skin biopsy. Serum allergen detection is of little significance for CAD diagnosis. Mast cells may be involved in the early process of CAD, while dendritic cells and tissue-resident memory T cell (TRM) may be related to the chronic process of the disease.

Chronic Actinic Dermatitis Revisited.

Chronic actinic dermatitis (CAD) is a persistent eczematous photodermatitis classically described in older, white men with contact allergy to plants. However, evidence from recent studies suggests that some demographics of CAD patients may be changing. The aims of the study were to determine the frequency of CAD in patients presenting with photosensitive eruptions and to identify the allergens and photoallergens most closely associated with this condition. We identified all patients with a diagnosis of CAD from 246 consecutive records of patients undergoing photopatch testing from July 1994 to June 2018 and summarized the demographics and test results in comparison with non-CAD patients. Nineteen (7.7%) of the 246 patients evaluated had CAD with a male-to-female ratio of 1:1.7 among CAD patients. Compared with non-CAD patients, photocontact allergy and/or contact allergy to sesquiterpene lactone mix and contact allergy to fragrances were significantly more common in CAD. Contact allergy to p-phenylenediamine was also common. The results of this study suggest that CAD presents in a broader demographic range, including both men and women of both light and dark skin types. Phototesting and photopatch testing should be considered when patients present with clinical findings consistent with CAD.

Chronic Actinic Dermatitis: a Review

To update readers on the current understandings of chronic actinic dermatitis (CAD) in regard to epidemiology, clinical findings, pathophysiology, treatment, and prognosis. CAD is classically thought to be primarily a disease of elderly Caucasian males, though recent evidence suggests that in skin of color, the disease manifests more often in younger females. Recent studies suggest the pathogenesis of CAD involves a type-IV hypersensitivity reaction, similar to allergic contact dermatitis. There is also evidence of resistance to UV-induced immunosuppression in these patients, similar to polymorphous light eruption (PMLE). Furthermore, a lower CD4/CD8 ratio on flow cytometry in CAD patients has been correlated with increased tissue burden of disease. Photoprotection remains a mainstay of treatment, though recent evidence suggests potential efficacy of tofacitinib or short courses of narrowband UVB phototherapy as treatment options. CAD is an immunologically mediated photodermatosis characterized by pruritic eczematous lesions of sun-exposed areas, most commonly seen in older Caucasian males. While the pathogenesis of the condition is not fully understood, a type-IV hypersensitivity reaction to UV-induced neoantigens is thought to play a role. Photoprotection remains the mainstay of treatment, though adjunctive treatments are rapidly emerging. Though considered a chronic condition, CAD tends to improve over time.

Evaluation of narrow band ultraviolet B phototherapy in the treatment of chronic actinic dermatitis in Chinese patients.

Few studies have been conducted in chronic actinic dermatitis (CAD) treated with narrowband ultraviolet B (NB UVB) phototherapy, especially in Asian patients. We aim to evaluate the efficacy and safety of NB UVB phototherapy in Chinese patients with CAD. 19 CAD patients of Fitzpatrick skin phototype IV received NB UVB phototherapy in spring and treatments were given 3 times weekly with incremental dose and maintenance therapy was given twice weekly for 3-4 weeks. The mean initial, endpoint, and cumulative dose of NB UVB was 0.08, 0.33, and 6.0 J/cm2 , respectively. Patients totally received 27 times of treatments in average. 87.5% of previously ultraviolet B（UVB） sensitive patients and 75% of previously ultraviolet A（UVA） sensitive patients had normal or improved MED after phototherapy. The percentage of patients returned to normal UVB phototesting was higher than that of patients returned to normal UVA phototesting (68.8% vs. 37.5%). The mean 1-week DLQI and the need for using immunosuppressive agents and antihistamines were significantly reduced after treatment (p < .01 or p < .05). In conclusion, prophylactic NB UVB phototherapy is effective and safe in treatment of CAD in Chinese patients with Fitzpatrick skin phototype IV.

Narrow-band ultraviolet B phototherapy regimens for the treatment of chronic actinic dermatitis and analysis of factors influencing treatment compliance

Objective To investigate the optimal regimen of narrow-band ultraviolet B (NB-UVB) phototherapy in the treatment of chronic actinic dermatitis (CAD) , and to analyze factors influencing treatment compliance. Methods Demographic data, results of photobiological tests, treatment parameters and clinical responses were collected from CAD patients who received NB-UVB phototherapy in Huashan Hospital affiliated to Fudan University from January 2008 to June 2015, and were reviewed retrospectively. Statistical analysis was done by using two independent samples t-test and chi-square test with SAS9.3 software to compare the clinical data between patients who completed and did not complete the NB-UVB phototherapy. Results A total of 79 CAD patients with Fitzpatrick skin type Ⅳ received NB-UVB phototherapy. Of these patients, 61 (77%) completed the whole treatment, while 18 (23%) dropped out because of intolerance to the NB-UVB radiation. Among the 61 patients who completed the treatment, the average initial, final and cumulative radiation doses of NB-UVB were (0.08 ± 0.01) J/cm2, (0.32 ± 0.08) J/cm2 and (5.9 ± 2.5) J respectively, and patients received (28 ± 8) times of treatment in average. When the radiation dose went up to 0.30 J/cm2, most skin lesions were cleared in 52 (85%) patients. A total of 19 patients received phototesting again after the end of phototherapy. Among 16 patients sensitive to ultraviolet A (UVA) before the treatment, 6 had normal minimal erythema dose to UVA (UVA-MED) , and another 6 had improved UVA-MED after the treatment. Among 16 patients sensitive to UVB before the treatment, 11 got normal UVB-MED and another 3 had improved UVB-MED after the treatment. Univariate analysis showed no significant differences in gender, age, duration of the disease, sensitivity to UVA and UVB radiation, results of photopatch test and patch test between the patients who completed and did not complete the treatment (all P > 0.05) . Conclusions The appropriate NB-UVB phototherapy for CAD patients should start at an initial radiation dose of 0.08 J/cm2 in spring and end at a final radiation dose of 0.30 J/cm2 for about 28 sessions, which can effectively reduce the photosensitivity to both UVA and UVB in CAD patients. Additionally, NB-UVB phototherapy can be applied in CAD patients of different gender, age, disease duration and photosensitive condition. Key words: Dermatitis, photoallergic; Ultraviolet therapy; Narrow-band ultraviolet ray; Phototest; Photopatch test

Photobiological responses in patients with chronic actinic dermatitis and their relationship with the melanocortin-1 receptor gene Arg163Gln variant: a preliminary study

Objective To explore differences in phototest and photopatch test results, and in skin color-related parameters between healthy subjects and patients with chronic actinic dermatitis (CAD), and to examine their relationship with the melanocortin-1 receptor gene (MC1R) Arg163Gln variant. Methods Phototests were performed by using a sun simulator SUN1000, and skin color was analyzed by using Hexameter MX18 in 25 patients with CAD and 25 healthy subjects. The MC1R genotype at position -163 was determined by PCR. Photopatch tests were performed on 25 patients with CAD and 5 healthy subjects using a standard series of photoallergens (RuiMin) and an ultraviolet (UV) phototherapy equipment, SS-03A. Results Regarding phototest results, both UVA-minimal persistent pigment darkening dose (MPPD) and UVB-minimal erythema dose (MED) were significantly lower in CAD patients compared with healthy controls (both P 0.05), but that of the CAA genotype differed significantly between the two groups (P < 0.01). UVA-MPPD and UVB-MED were both significantly lower in CAD patients with the CAA genotype at position-163 in the MC1R gene than in those without the genotype (P = 0.055, 0.325, respectively). Conclusions Skin photobiological testing plays a critical role in the diagnosis of CAD. Further studies are needed to clarify the role of the CAA genotype at position-163 in the MC1R gene in the diagnosis, prevention and treatment of CAD. Key words: Photosensitivity disorders; Pigmentation; Genes, Arg163Gln; Chronic actinic dermatitis; Photopatch tests

Patch and photo patch test in suspected chronic actinic dermatitis patients

Patch and photo patch test in suspected chronic actinic dermatitis patients

Contact and photocontact sensitization in chronic actinic dermatitis: a changing picture

Patients with chronic actinic dermatitis (CAD) frequently have positive patch or photopatch tests. In our previous study (period 1987-1992), the most prominent contact allergen was the sesquiterpene lactone mix (36% of patients with CAD). To assess whether contact allergy profiles in CAD patients between 2000 and 2005 have changed in respect to our previous data (1987-1992). Fifty CAD patient records from 2000 to 2005 for patch and photopatch testing were retrospectively analysed and data were compared with that from 86 patients seen between 1987 and 1992. Thirty-two (64%) and 64 (74%) patients had positive patch or photopatch tests in 2000-2005 and 1987-1992, respectively. The allergen profile has altered. A decline in sesquiterpene lactone mix positive reactions was noted: 29 (36%) patients were positive in 1987-1992 and 10 (20%) patients in 2000-2005, but this was not significant (P = 0.08). Reactions to non-fragrance consumer allergens (i.e. p-phenylenediamine and preservatives) had risen from 7 reactions (1987-1992) to 21 reactions in 13 individuals (2000-2005) (P < 0.001). Of these allergens, p-phenylenediamine was the most common (12%; P = 0.004). A significant rise in positive patch tests to non-fragrance consumer allergens, particularly p-phenylenediamine, was seen in CAD patients in 2000-2005. We speculate this alteration of allergen profile may be partly due to changes in exposure patterns.

A Korean experience with chronic actinic dermatitis during an 18‐year period: meteorological and photoimmunological aspects

The authors noted that chronic actinic dermatitis (CAD) increased in connection with increased sun exposure and believed that there may be a correlation between the two. The purpose of this study was to determine the relationship between increased sun exposure and CAD. We also applied a clinical severity scoring system to determine the correlation with various laboratory parameters. We investigated trends in sun exposure in Pusan during an 18-year period. We conducted photopatch/patch testing in 51 CAD patients. We also determined the total IgE, percentage of eosinophils, and chemokine receptor profiles in the peripheral blood and analyzed correlations between laboratory data and the clinical severity of CAD. A close correlation was demonstrated between the number of CAD patients and increased sun exposure. Positive patch test reactions and positive photopatch reactions were observed in 35 and 41 of the 51 tested patients, respectively. The total IgE levels were higher in the severe group than in the others. CCR4 expression increased in parallel with clinical severity. Korean patients may have increased susceptibility to CAD with increased sun exposure. We believe that the majority of the CAD patients tested had photoallergy and contact allergy. The clinical severity seemed to correlate well with the total IgE level and CCR4 expression.

The role of interleukins 1, 6 and 8 as lymphocyte attractants in the photodermatoses polymorphic light eruption and chronic actinic dermatitis.

The two photodermatoses, polymorphic light eruption (PLE) and chronic actinic dermatitis (CAD), are characterized by lymphocyte-rich inflammatory infiltrates, the pathogeneses of which are not fully understood. We have therefore studied suction blister fluid (SBF) samples from patients with these conditions before and at two time points after the induction of experimental lesions by means of a solar simulator; this SBF was then tested for the presence of selected cytokines known to induce peripheral blood lymphocyte (PBL) migration in vitro. A specific EL-4 NOB-1 bioassay was used to detect interleukin (IL)-1 activity, which has already been noted in normal skin and this was found in pre-irradiation control samples as well as 1-3 h and 24 h post-irradiation in both patient groups, but at levels not significantly different from those of controls. Use of a B9 cell proliferation assay showed no detectable IL-6-like activity pre-irradiation, but there was substantial activity in samples at both post-irradiation time points in both patient groups. Further, in other experiments, retained SBF samples were tested in an in vitro PBL migration assay in the presence and absence of neutralizing antibodies against IL-1 alpha, IL-1 beta, IL-6 and IL-8; considerable PBL attractant activity was noted in the pre-irradiation SBF from both patient groups; a finding consistent with previous reports of such activity in samples from normal skin, and at least in CAD patients, a proportion of this activity appeared to be due to IL-1, pre-incubation of SBF with neutralizing antibodies against IL-1 alpha and IL-1 beta reducing the effect significantly. Substantial PBL attractant activity was present also in the SBF from 1-3 h and 24 h post-irradiation samples in both patient groups and again, IL-1 neutralizing antibodies reduced this in the 1-3 h and 24 h CAD samples. In addition, neutralizing antibodies against IL-6 and IL-8 reduced the activity in the 24 h PLE samples significantly and although not fully conclusive in the case of IL-1, these data suggest that IL-6, IL-8 and possibly IL-1 may be involved in the induction of PBL infiltrates, and perhaps other events, in both PLE and CAD.

A prospective longitudinal study of the outdoor behaviour and symptoms of photosensitive patients

The purpose of this study was to determine the measures that photosensitive patients use to control their sun exposure. Each week from March until September 1995, 30 patients with polymorphic light eruption (PLE) and 17 patients with chronic actinic dermatitis (CAD) returned a set of reply paid postcards on which they recorded information about their outdoor behaviour and symptoms. The principal differences between the two groups were that CAD patients had a much greater incidence of symptoms despite making more use of protective measures such as covering arms, wearing hats and applying sunscreen, than patients with PLE. And that as summer approached the PLE patients spent more time outdoors, whereas there was less seasonal variation in this respect among CAD patients. Tentative conclusions drawn from mathematical modelling indicated that the incidence of rash on a particular day was influenced by ambient ultraviolet radiation and length of time spent outdoors. There were indications that wearing a hat and keeping the arms covered offered some protection, whereas use of sunscreen may actually increase the likelihood of symptoms.

A study of the kinetics and pattern of E-selectin, VCAM-1 and ICAM-1 expression in chronic actinic dermatitis

It has been postulated that chronic actinic dermatitis (CAD), an eczematous photodermatosis, is a type IV hypersensitivity reaction. Expression of adhesion molecules on dermal blood vessels is critical to the recruitment of inflammatory cells into the skin; the pattern and kinetics of upregulation of these molecules in the skin differ following ultraviolet irradiation and delayed hypersensitivity reactions. We therefore investigated the kinetics of expression of endothelial leucocyte adhesion molecules (E-selectin) vascular-cell adhesion molecules 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) in CAD lesions induced by suberythemal solar-stimulated radiation, by immunohistochemical staining of biopsies taken at 1-168 h after irradiation. In control, unirradiated skin from CAD patients, baseline vessel-associated and interstitial ICAM-1, and vessel-associated VCAM-1 were noted; focal keratinocyte ICAM-1 expression was observed in two of the five patients. Endothelial E-selectin, and vessel-associated and interstitial VCAM-1 expression, were upregulated in induced lesions by 1-5 h in all patients, and remained elevated at 120-168 h. Vessel associated, dermal interstitial, and keratinocyte ICAM-1 expression was upregulated in all patients at 24 h, and remained increased at 120-168 h. These findings differ from those observed following ultraviolet irradiation of normal skin, and resemble those seen in normal skin during a delayed-type hypersensitivity reaction, supporting the hypothesis that CAD involves a type IV response to an as yet unidentified photo-induced antigen.

Immunologic Differentiation of the Sézary Syndrome Due to Cutaneous T-Cell Lymphoma and Chronic Actinic Dermatitis

Peripheral blood mononuclear cells from two well-defined groups of patients with the Sézary syndrome have been studied employing indirect immunofluorescent and indirect immunogold techniques in light and electron microscopy, using monoclonal antibodies against T-cell subpopulations. Four patients had chronic actinic dermatitis (CAD) of the actinic reticuloid variant, with erythroderma. Eight patients had cutaneous T-cell lymphoma. All patients showed the clinical features of the Sézary syndrome, including erythroderma, palmoplantar hyperkeratosis, and peripheral lymphadenopathy, and in all patients significant numbers (0.5-30.5 X 10(9) cells/liter) of circulating mononuclear cells were observed with Sézary cell morphology on light-microscopic examination of blood films. Major differences were observed in the circulating T-cell subpopulations in the two groups. In the erythrodermic CAD patients, there was a moderately elevated T-cell count (1.6 +/- 0.6 X 10(9) cells/liter; normal, 1.0 +/- 0.3 X 10(9) cells/liter) of which the majority of the cells was suppressor T cells (OKT8+) giving a very low helper:suppressor T-cell ratio of 0.1:1-0.36:1 (normal, 1.7:1-3.5:1). In cutaneous T-cell lymphoma, there was also an elevation of the T-cell count (9.5 +/- 12.9 X 10(9) cells/liter), but in these patients the predominant cell was the helper T cell (OKT4+) with a high helper:suppressor T-cell ratio of 3.7:1-98:1.