Human Leukocyte Antigen Markers for Distinguishing Pustular Psoriasis and Adult-Onset Immunodeficiency with Pustular Reaction.

Pustular skin diseases, with pustular psoriasis (PP) being the prototype, are immune-mediated diseases characterized by the presence of multiple pustules, resulting from neutrophil accumulation in the layer of epidermis. Sterile skin pustular eruption, like PP, is also observed in 20-30% of patients with adult-onset immunodeficiency syndrome (AOID) and anti-interferon γ autoantibodies (IFN-γ), leading to challenges in classification and diagnosis. While the mechanism underlying this similar phenotype remains unknown, genetic factors in relation to the immune system are suspected of playing an important role. Here, the association between human leukocyte antigen (HLA) genes, which play essential roles in antigen presentation, contributing to immune response, and the presence of skin pustules in AOID and PP was revealed. HLA genotyping of 41 patients from multiple centers in Thailand who presented with multiple sterile skin pustules (17 AOID patients and 24 PP patients) was conducted using a next-generation-sequencing-based approach. In comparison to healthy controls, HLA-B*13:01 (OR = 3.825, 95%CI: 2.08-7.035), C*03:04 (OR = 3.665, 95%CI: 2.102-6.39), and DQB1*05:02 (OR = 2.134, 95%CI: 1.326-3.434) were significantly associated with the group of aforementioned conditions having sterile cutaneous pustules, suggesting a common genetic-related mechanism. We found that DPB1*05:01 (OR = 3.851, p = 0.008) and DRB1*15:02 (OR = 3.195, p = 0.033) have a significant association with pustular reaction in AOID patients, with PP patients used as a control. A variant in the DRB1 gene, rs17885482 (OR = 9.073, p = 0.005), was observed to be a risk factor for PP when using AOID patients who had pustular reactions as a control group. DPB1*05:01 and DRB1*15:02 alleles, as well as the rs17885482 variant in the DRB1 gene, were proposed as novel biomarkers to differentiate PP and AOID patients who first present with multiple sterile skin pustules without known documented underlying conditions.

Comparative immunohistochemical analysis of inflammatory cytokines in distinct subtypes of Sweet syndrome.

Background: A dysregulated immune response has been implicated in Sweet syndrome (SS) pathogenesis; however, cytokine profiles across different conditions associated with SS - including adult-onset immunodeficiency (AOID) due to anti-interferon (IFN)-γ autoantibodies - remain unknown. Objective: To investigate alterations in inflammatory cytokines in skin lesions of distinct subtypes of SS. Methods: Skin biopsies were collected from 42 AOID- and 52 non-AOID-associated SS patients and 18 healthy controls. The comparative immunohistochemical study was conducted using monoclonal antibodies against interleukin (IL)-1ß, IL-6, IL-17, IFN-γ, and tumor necrosis factor-α on paraffin-embedded sections. The quantitative percentage positivity and intensity were calculated using computer-based image analysis. Results: The results showed stronger and more diffuse dermal immunoreactivity for IFN-γ and IL-17 in the AOID-associated (p < 0.001 and p < 0.001, respectively) and non-AOID-associated SS (p < 0.001 and p < 0.001, respectively) groups. However, no significant differences in the levels of these two cytokines were observed between the AOID- and non-AOID-associated SS groups. Increased expression of IFN-γ together with IL-17 was also noted in almost all subtypes among non-AOID-associated SS. Conclusions: These results demonstrate that IFN-γ and IL-17 are implicated in immunopathology of all SS subtypes, including AOID-associated SS, despite the presence of anti-IFN-γ autoantibodies.

Increased tissue expression of IL-31 in patients with psoriasis.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis remains unclear. Although many studies have demonstrated the role of serum interleukin-31 (IL-31) in psoriasis, only one study has examined histopathological expression in lesional skin. This study aimed to investigate the expression of IL-31 in skin biopsy specimens of psoriasis patients compared to healthy subjects and identify its possible correlation to disease severity and itch intensity. Psoriasis patients and healthy volunteers were recruited. Four-millimeter punch biopsy was performed at the lesional skin of psoriasis patients and normal skin of healthy subjects. Expression of IL-31 was measured by immunohistochemistry. Baseline characteristics, disease activity, itch intensity, and related laboratory results were collected. Twenty-six biopsy specimens of psoriasis patients and 10 tissue samples of healthy subjects were evaluated. Epidermal and dermal psoriasis lesions had significantly higher IL-31 expression compared to the healthy skin (P < 0.001). However, there was no significant difference in lesional expression of IL-31 by disease severity or itch intensity. Increased IL-31 expression in the lesions of psoriasis patients suggests the involvement of IL-31 in the pathogenesis of psoriasis.

SERPINB3, Adult-Onset Immunodeficiency, and Generalized Pustular Psoriasis.

BACKGROUND: Generalized pustular psoriasis (GPP; MIM 614204) is a rare and severe pustular autoinflammatory skin disease in which acute generalized erythema and scaling develop with numerous sterile pustules. GPP shares skin manifestations, especially pustular skin reaction, with adult-onset immunodeficiency (AOID) with anti-interferon-γ autoantibodies, an autoimmune disease. METHODS: Clinical examinations and whole-exome sequencing (WES) were performed on 32 patients with pustular psoriasis phenotypes and 21 patients with AOID with pustular skin reaction. Immunohistochemical and histopathological studies were performed. RESULTS: WES identified three Thai patients presenting with similar pustular phenotypes-two with a diagnosis of AOID and the other with GPP. A heterozygous missense variant chr18:g.61325778C>A NM_006919.2: c.438G>T; NP_008850.1: p.Lys146Asn; rs193238900 in SERPINB3 was identified in two patients: one with GPP and the other with AOID. The other patient who had AOID carried a heterozygous missense variant chr18:g.61323147T>C NM_006919.2: c.917A>G; NP_008850.1: p.Asp306Gly in SERPINB3. Immunohistochemical studies showed overexpression of SERPINA1 and SERPINB3, a hallmark of psoriatic skin lesions. CONCLUSIONS: Genetic variants in SERPINB3 are associated with GPP and AOID with pustular skin reaction. The skin of patients with GPP and AOID carrying SERPINB3 mutations showed overexpression of SERPINB3 and SERPINA1. Clinically and genetically, GPP and AOID appear to share pathogenetic mechanisms.

Factors Associated With Refractoriness to an Up to Fourfold Dosage of Antihistamines in Isolated Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease and has a significant impact on patients' quality of life. The aim of treatment is complete symptom control. AIM: To identify potential factors associated with antihistamine-refractory isolated CSU and to determine the factors that predict response to second-generation H1 antihistamines at dosages from one- to fourfold. METHODS: We conducted a retrospective cohort study, which included adult patients diagnosed with isolated CSU and had complete symptom control. Clinical and laboratory findings were compared between the patients who were responsive to second-generation H1 antihistamines (< fourfold) and those who were refractory to a fourfold dose. Clinical and laboratory data were compared by dosage in the antihistamine-responsive group. RESULTS: There were 182 isolated CSU patients who met the study criteria, of whom 150 (82.4%) were responsive to treatment with up to a fourfold dose of second-generation H1 antihistamines, while 32 (17.6%) were refractory. In univariate analysis, age at onset, body mass index, baseline Urticaria Activity Score-7 (UAS7), white blood cell count, total neutrophil count, neutrophil-lymphocyte ratio, platelet count, and new generation antihistamines were significantly higher in the antihistamine-refractory group. According to multivariate analysis, baseline UAS7 was the only independent factor associated with antihistamine-refractory isolated CSU (odds ratio 1.14, 95% CI 1.01-1.28, P = .03). In the antihistamine-responsive group, white blood cell count tended to predict response to antihistamine treatment (P < .001, 0.04, 0.34 between onefold and twofold, twofold and threefold, and threefold and fourfold, respectively). CONCLUSION: Baseline UAS7 was an independent factor associated with antihistamine-refractory isolated CSU.

Increased IL-31 expression in serum and tissue protein in prurigo nodularis.

Background: Prurigo nodularis (PN) is a chronic pruritic skin disease which can greatly impact patients' quality of life. Moreover, the pathogenesis remains unclear, making it a difficult-to-treat condition. Aims: To investigate the expression of interleukin-31 (IL-31) in serum and skin biopsy specimens of PN patients and healthy subjects and identify its possible correlation to disease severity and itch intensity. Methods: Patients with PN and healthy volunteers were recruited for the study. Expression levels of IL-31 were measured by enzyme-linked immunosorbent assay and immunohistochemistry. Baseline characteristics, disease activity, itch intensity, and related laboratory results were collected. Results: Forty-three PN patients and 31 healthy subjects participated in our study. The PN patients had significantly higher mean serum IL-31 levels than the healthy subjects (52.9 ± 18.2 versus 36.3 ± 10.7 pg/ml, p < 0.001). Epidermal and dermal PN lesions also exhibited significantly higher IL-31 expression compared with the healthy skin (p < 0.001 and p = 0.01, respectively). However, there was no significant difference in serum or lesional expression of IL-31 by disease severity or itch intensity. Conclusion: Increased IL-31 expression in serum and PN lesions suggests that IL-31 has a potential role in the pathogenesis of PN.

Comparison of the clinical efficacy of subcutaneous vs. oral administration of methotrexate in patients with psoriasis vulgaris: a randomized controlled trial.

BACKGROUND: Evidence demonstrates that parenteral administration of methotrexate (MTX) has a higher drug bioavailability than oral administration. This difference is even more pronounced for medium to high dosages. AIM: To compare the efficacy, safety, and tolerability of oral and subcutaneous (SC) MTX for treatment of psoriasis. METHODS: A randomized, comparative, single-blind, 32-week study was conducted. The clinical response was evaluated using the Psoriasis Area Severity Index (PASI) and patient global satisfaction was assessed using a visual analogue scale (VAS). RESULTS: In total, 77 completed the study: 38 in the SC and 39 in the oral MTX group. No significant between-group differences were found in the number attaining PASI improvement of 75% (PASI75), 90% (PASI90) and 100% (PASI100) at Weeks 16 and 32: PASI75 (P = 0.14 and P = 0.21, respectively), PASI90 (P = 0.23 and P = 0.18) and PASI100 (P = 0.62 and P = 0.22). According to the mean VAS, no significant differences between the groups were found at any time points except at Week 32 that the mean VAS was significantly higher in the SC group (P = 0.03). Adverse events were comparable in both groups. CONCLUSION: SC and oral administration of MTX had similar efficacies in improving the PASI score even at the highest tolerable dose; however, the SC MTX group had higher overall patient satisfaction than the oral MTX group. No difference in tolerability was found.

Loss of Function TGFBR2 Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency.

BACKGROUND: Generalized pustular psoriasis (GPP; MIM 614204) is a rare multisystemic autoinflammatory disease, characterized by episodes of acute generalized erythema and scaling developed with the spread of numerous sterile pustules. Adult-onset immunodeficiency syndrome (AOID) with anti-interferon-γ autoantibodies is an immunodeficiency disorder associated with disruptive IFN-γ signaling. METHODS: Clinical examination and whole exome sequencing (WES) were performed on 32 patients with pustular psoriasis phenotypes and 21 patients with AOID with pustular skin reaction. Histopathological and immunohistochemical studies were performed. RESULTS: WES identified four Thai patients presenting with similar pustular phenotypes-two with a diagnosis of GPP and the other two with AOID-who were found to carry the same rare TGFBR2 frameshift mutation c.458del; p.Lys153SerfsTer35, which is predicted to result in a marked loss of functional TGFBR2 protein. The immunohistochemical studied showed overexpression of IL1B, IL6, IL17, IL23, IFNG, and KRT17, a hallmark of psoriatic skin lesions. Abnormal TGFB1 expression was observed in the pustular skin lesion of an AOID patient, suggesting disruption to TGFß signaling is associated with the hyperproliferation of the psoriatic epidermis. CONCLUSIONS: This study implicates disruptive TGFBR2-mediated signaling, via a shared truncating variant, c.458del; p.Lys153SerfsTer35, as a "predisposing risk factor" for GPP and AOID.

SERPINA1, generalized pustular psoriasis, and adult-onset immunodeficiency.

Adult-onset immunodeficiency syndrome (AOID) with anti-interferon (IFN)-γ autoantibodies is characterized by an AIDS-like illness with disruptive IFN-γ signaling. Patients generally present with recurrent and disseminated opportunistic infections along with neutrophilic dermatoses. Generalized pustular psoriasis (GPP; Online Mendelian Inheritance in Man #614204) is characterized by acute generalized erythema and scaling with numerous aseptic pustules. Mutations in SERPINA3 have been reported as predisposing risk factors for both AOID and GPP. Here, we report two unrelated patients, one with AOID and a pustular skin reaction and the other with GPP, who both carried the same heterozygous variant c.718G>A (p.Val240Met) in SERPINA1. Our observation of a shared mutation in SERPINA1 in AOID and GPP indicate possible pathobiological and disease mechanism similarities in these two disorders. Thus, variants in both SERPINA1, SERPINA3, and potentially other SERPIN family members may be associated with the etiology of GPP and AOID.

Increased serum IL-31 levels in chronic spontaneous urticaria and psoriasis with pruritic symptoms.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common pruritic skin condition, the pathogenesis of which remains unclear. Interleukin-31 (IL-31) is a major pruritogenic cytokine that plays a role in inducing pruritus in various skin diseases. AIM: To 1) compare serum IL-31 levels among CSU patients, psoriasis patients with pruritic symptoms, and healthy subjects, 2) examine the correlations between serum IL-31 levels and disease severity, and 3) compare IL-31 levels in patients with and without CSU-associated auto-antibodies. METHODS: Patients with CSU, psoriasis with pruritic symptoms, and healthy volunteers were recruited in the study. Serum IL-31 levels were measured with commercial kits. Baseline characteristics, urticaria activity score, psoriasis area severity index, pruritic intensity score, and related laboratory results were collected. RESULTS: Sixty-five CSU patients, 30 psoriasis patients who had pruritus, and 31 healthy subjects participated in our study. The CSU patients had significantly higher mean serum IL-31 levels than the psoriasis patients (252.4 ± 115.5 vs 121.4 ± 16.6 pg/mL, P < 0.001). Both CSU and psoriasis patients also had significantly higher mean serum IL-31 when compared with the healthy subjects. Serum IL-31 levels of CSU and psoriasis patients did not differ significantly according to disease or itching severity. Thyroid antibodies and antinuclear antibodies were positive in 22 (33.8%) and 28 (43.1%) CSU patients, respectively. The CSU patients with ANA titers ≥1:160 had significantly higher mean serum IL-31 levels than in those who were negative for ANA and those with titers of 1:80 (P < 0.003 and P < 0.008, respectively). CONCLUSION: Higher serum IL-31 levels were found in patients with CSU and psoriasis with pruritic symptoms. This suggests that IL-31 has a possible role in the pathogenesis of CSU and psoriasis with pruritic symptoms.

Interleukin-31 and Chronic Pruritus of Unknown Origin.

Chronic pruritus of unknown origin (CPUO) is a refractory condition. The expression of Interleukin-31 (IL-31), a major pruritogenic cytokine, in CPUO patients has not been investigated. This study aimed to investigate the potential association of IL-31 with CPUO. This was a cross-sectional, analytical study. Patients diagnosed with CPUO and healthy subjects were included at a ratio of 1:2. Serum IL-31 levels were measured in both groups and compared. There were 10 CPUO and 20 healthy subjects who participated in this study. The median IL-31 level in the CPUO group was significantly higher than in the healthy group (127.3 vs 34.4 pg/mL; P < .001). The presence of CPUO was independently associated with IL-31 levels with a coefficient of 89.678 (P < .001). The serum IL-31 cutoff point for CPUO was 56.8 pg/mL, with an area under the receiver operating characteristic curve (ROC) of 100%. Chronic pruritus of unknown origin was significantly and independently associated with higher IL-31 levels. Further clinical trials of IL-31-related treatment may be justified in CPUO patients.

Acral Cutaneous Ulcerations and Livedo Reticularis with Rapidly Progressive Interstitial Lung Disease in Anti-MDA5 Antibody-Positive Classical Dermatomyositis.

Rapidly progressive interstitial lung disease (RP-ILD) and its distinctive cutaneous features are highly associated with the presence of anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody in patients with dermatomyositis (DM), leading to a poor prognosis. We describe the case of a 25-year-old man who developed progressive proximal muscle weakness with RP-ILD and had unusual cutaneous findings (cutaneous ulcerations and livedo reticularis) accompanied by classical cutaneous features (heliotrope rash, Gottron's papules, Gottron's sign, and flagellate erythema). Blood test was positive for anti-MDA5 antibody. He was treated with intravenous corticosteroids and immunoglobulin, but passed away due to respiratory failure within 1 month after admission. Our case highlights that the presence of cutaneous ulcerations and livedo reticularis, in addition to RP-ILD, are useful clinical clues that may aid in the detection of anti-MDA5 antibody, early initiation of combined immunosuppressants, and prognosis prediction in patients with classical DM.

Oral Polypodium Leucotomos Extract and Its Impact on Visible Light-Induced Pigmentation in Human Subjects

BACKGROUND: Visible light (VL) has multiple effects on the skin that currently available sunscreens do not protect against. Polypodium leucotomos extract (PLE) has properties that may offer protection against VL. OBJECTIVES: To determine the effectiveness of PLE in preventing VL-induced effects. METHODS: Twenty-two subjects with Fitzpatrick skin phototype IV-VI were enrolled. On day 0, subjects were irradiated with VL. Clinical Investigator's Global Assessment (IGA) scoring and spectroscopic evaluations were performed immediately, 24 hours, and 7 days after irradiation. Subjects then received a 28-day supply of PLE (480 mg daily). Irradiation and evaluation were repeated. Three 4-mm punch biopsies were obtained for immunohistochemistry analysis: one from normal unirradiated skin and the other two twenty-four hours after irradiation, pre- and post-PLE, from sites irradiated with highest dose of VL. RESULTS: All subjects had immediate pigment darkening, persistent pigment darkening, and delayed tanning both pre- and post-PLE. For the highest VL dose (480 J/cm²) spectroscopic assessments demonstrated a statistically significant decrease in persistent pigment darkening and delayed tanning post-PLE. In addition, there was a significant decrease in cyclooxygenase-2, and a trend towards decreases in the markers for cellular damage post-PLE. While there was a trend towards lower IGA scores post-PLE, statistical significance was not reached possibly due to lack of sensitivity of the visual IGA scoring system in detecting small changes. CONCLUSIONS: Spectroscopic data and immunohistochemistry indicate an effect of PLE on visible light induced effects. As such, PLE may be used as an adjuvant to traditional means of photoprotection to protect against the effects of VL. Clinical trial registration number: NCT02904798. J Drugs Dermatol. 2019;18(12):1198-1203.

Spectral characteristics of visible light-induced pigmentation and visible light protection factor.

Solar radiation is a major contributor to the development of skin cancer. Recent studies have shown that visible light (VL), a major portion of solar spectrum, induces biologic effects on the skin. Ultraviolet filters in currently available broad-spectrum sunscreens do not offer protection against VL. This study was designed to identify the spectral characteristics of the skin responses induced by VL, which can be utilized for time efficient in vivo VL testing. Thirty-one subjects were irradiated with a light source emitting visible light with less than 0.5% long wavelength UVA1 (VL + UVA1, 370-700 nm), and 41 subjects were irradiated with pure visible light (pure VL, 400-700 nm). Assessments including clinical photography, investigator's global assessment of pigmentation and erythema, and diffuse reflectance spectroscopy (DRS) performed immediately and seven days after irradiation. Clinical and spectroscopic data showed that VL + UVA1 spectral output induced significantly darker and persistent skin responses as compared to those induced by pure VL. Spectroscopic signatures of skin responses induced by both radiation sources were identified. The signatures were found to be specific to the radiation source and time of collection. A method to evaluate VL protection factor, using quantitative information from the spectral signatures obtained, was proposed.

Coexistence of Fungal Infections in Psoriatic Nails and their Correlation with Severity of Nail Psoriasis.

BACKGROUND: Nail involvement in psoriasis is often complicated by concomitant fungal infections. The aim of this study was to investigate the prevalence of fungal infections in nail psoriasis and correlate it with the severity of nail psoriasis. MATERIALS AND METHODS: This retrospective study included patients with nail psoriasis aged ≥18 years with at least one fingernail and one toenail involvement who were treated at Siriraj Hospital from September 2012 to January 2014. Severity of nail psoriasis was assesed by Nail Psoriasis Area Severity Index (NAPSI) score. The nail clippings from the the least and most severely involved psoriatic fingernails and toenails were cultured to determine the presence of coexisting fungal infections and isolate the fungal species. RESULTS: Sixty-two patients (33 males, 29 females) fulfilling the inclusion criteria were included in the study. The mean age at the time of presentation was 51.3 years mention SD. The most common nail change consistent with psoriasis was onycholysis, followed by subungual hyperkeratosis. The most commonly isolated fungi in the most severely affected fingernails were Candida spp. (41.9%) manifesting as paronychia in 5 patients (19.2%). The most commonly isolated fungi in the most severely affected toenails were nondermatophytes (NDMs) other than candida (32.3%). Dermatophytes were not detected from any of the psoriatic nails. The fungal species isolated from the most severely affected fingernails were significantly different than the isolated fungal species in the most severely affected toenails (P = 0.026). Fungal organisms were identified in 32.3% of the most severely affected fingernails and in 27.4% of the most severely affected toenails. The overall rate of isolation of fungus was significantly significantly higher in severely affected nails than in the least affected nails (P < 0.005). CONCLUSION: A high rate of concomitant fungal infections, especially yeasts and NDMs, was found in psoriatic nail patients. The rate of isolation of fungal species was higher in severely involved psoriatic nails than mildly involved ones. The spectrum of fungal species isolated from the the severely involved toenails and fingernails were also different from each other. These organisms may be true pathogens that cause onychomycosis or their presence may reflect colonization, contamination, or concurrent infection.

The treatment outcomes and dose de-escalation of desloratadine up-dosing in chronic spontaneous urticaria.

BACKGROUND: An increase in dosages up to fourfold of second generation antihistamines is recommended for recalcitrant chronic spontaneous urticaria (CSU). No regimen guidelines about dose de-escalation, however, are mentioned once the disease is controlled. OBJECTIVE: To demonstrate the treatment outcomes and dose reduction in desloratadine assessed using the urticarial activity score over 7 consecutive days. METHODS: Medical records of all patients with CSU treated with desloratadine were collected retrospectively during a period from January 2010 to December 2013. RESULTS: Sixty-seven (94.4%) patients had remission of the disease with variable doses of desloratadine. The patients who had CSU concomitant with antithyroid antibodies or high erythrocyte sedimentation rates had a greater tendency not to respond to the standard dose. Once the disease was completely controlled, 67 patients finished the treatment, but 63 (94%) patients had recurrent symptoms. Sixty-three patients took the same dose that induced the response for a further 4 weeks before stopping or reducing the dose, 41/63 (65.1%), however developed urticaria again. Forty-one patients took the same dose for a further 8 weeks; only 2/41 (4.9%) patients developed the rash again. The mean follow-up period after the disease was controlled was 7.5 months. CONCLUSION: Most patients need higher than the standard doses to obtain remission. Once the disease is completely controlled, however, maintenance of the same dosage for at least 8 weeks before dose reduction is suggested in order to avoid recurrence of the symptoms.

Postinflammatory hyperpigmentation: A comprehensive overview: Epidemiology, pathogenesis, clinical presentation, and noninvasive assessment technique.

Postinflammatory hyperpigmentation (PIH) commonly occurs after various endogenous and exogenous stimuli, especially in dark-skinned individuals. PIH is one of the most common complications of procedures performed using laser and other light sources. The severity of PIH is determined by the inherent skin color, degree and depth of inflammation, degree of dermoepidermal junction disruption, inflammatory conditions, and the stability of melanocytes, leading to epidermal and dermal melanin pigment deposition. The depth of melanin pigment is the key factor to predict prognosis and treatment outcome. Epidermal hyperpigmentation fades more rapidly than dermal hyperpigmentation. Various inflammatory disorders can eventually result in PIH. The evaluation of pigmentation using noninvasive tools helps define the level of pigmentation in the skin, pigmentation intensity, and guides therapeutic approaches. This first article in this 2-part series discusses the epidemiology, pathogenesis, etiology, clinical presentation, differential diagnoses, and investigation using noninvasive assessment techniques that objectively determine the details of pigmentation.

Postinflammatory hyperpigmentation: A comprehensive overview: Treatment options and prevention.

Postinflammatory hyperpigmentation (PIH) occurs after various dermatoses, exogenous stimuli, and dermatologic procedures. The clinical course of PIH is chronic and unpredictable, although the probability of resolution of epidermal hyperpigmentation is better than those of dermal hyperpigmentation. PIH can be prevented or alleviated. When it does occur, the underlying inflammatory conditions should be sought and treated as the first step to reduce the progression of inflammation and PIH (which is an inflammatory consequence). If the inflammatory conditions subsides or there is no evidence of inflammation at the time of diagnosis, the treatments of PIH should be considered as the next step. Understanding the available treatment options helps the physician choose the appropriate treatment for each patient. Having a reproducible model for PIH is essential for the development of treatment modalities. The second article in this 2-part continuing medical education series on PIH specifically addresses the evidence that supports medical and procedural treatments of PIH and other forms of acquired hyperpigmentation. It also describes a PIH model and provides an algorithm for clinical practice along with discussion about the prevention of PIH.

Phototherapy in systemic sclerosis: Review.

Systemic scleroderma-also known as systemic sclerosis (SSc)-is a chronic systemic connective tissue disease characterized by collagen deposition in cutaneous and internal organs, leading to skin sclerosis and multiple organ fibrosis. The pathogenesis is complex and remains poorly understood. Treatment is based on organ involvement and requires a multidisciplinary approach. Skin sclerosis can cause disability, leading to decreasing quality of life. Various systemic antifibrotic therapies have been used; however, most have unsatisfactory results. Recently, phototherapy and in particular ultraviolet A (UVA) has been used to treat skin sclerosis in SSc patients with satisfactory results. The main mechanisms include lymphocyte apoptosis, cytokine alteration, inhibition of collagen synthesis and increased collagenase production, and neovascularization, leading to the breakdown of collagen fibrils resulting in skin softening or even healing digital ulcers. Most studies reported that psoralen plus UVA (PUVA) and UVA1 phototherapy improved clinical outcomes vis-à-vis skin sclerosis, joint mobility, ulcers, and histopathology. PUVA and UVA1 phototherapy therefore have potential as an alternative or adjunctive therapy for patients with SSc.

Clinical features and outcomes of Sweet's syndrome associated with non-tuberculous mycobacterial infection and other associated diseases.

Sweet's syndrome (SS) is associated with various diseases including non-tuberculous mycobacterial infection (NTM). Recent reports have shown that SS associated with NTM is increasing. Clinical features of SS associated with NTM may be different from SS associated with other associated diseases. The aim of the present study was to compare clinical parameters and treatment outcomes of SS associated with NTM and other associated diseases. Patients from January 2004 to April 2014 diagnosed with SS were retrospectively enrolled. Clinical variables were compared between SS patients with and without NTM infection. There were 51 SS patients during the study period; 36 patients (70.59%) had NTM. Clinical variables between the NTM and other associated diseases were comparable: age, sex, and pattern and locations of skin lesions. Five laboratory factors were significantly different between the groups including white blood cell counts (NTM 25 800 vs 12 850 cells/mm(3) ), lymphocyte percentages (13.0% vs 18.7%), monocytes (3.0% vs 7.2%), blood urea nitrogen (BUN) (11.7 vs 8.1 mg/dL) and serum creatinine (Cr) (1.0 vs 0.7 mg/dL). The presence of markedly high white blood cell counts, a low percentage of mononuclear cells and high BUN/Cr levels in SS may be a clinical clue to recognize the association with NTM infections; particularly in dissemination.