Autoimmune Skin Disease Research Articles

140 Comparative scRNA-Seq profiling of four autoimmune skin diseases points to CXCL13 as a potential player in skin autoimmunity

140 Comparative scRNA-Seq profiling of four autoimmune skin diseases points to CXCL13 as a potential player in skin autoimmunity

1099 Rational development of JAK1-selective siRNA therapeutics for the treatment of autoimmune skin diseases

1099 Rational development of JAK1-selective siRNA therapeutics for the treatment of autoimmune skin diseases

092 Opsonization of the bullous pemphigoid antigen BP180 by complement component 3-derived fragments may precipitate autoimmune skin disease

092 Opsonization of the bullous pemphigoid antigen BP180 by complement component 3-derived fragments may precipitate autoimmune skin disease

674 The impact of race on the health outcomes of the autoimmune skin disorder pemphigus vulgaris

674 The impact of race on the health outcomes of the autoimmune skin disorder pemphigus vulgaris

Lichen planus – A refractory autoimmune disorder

Lichen planus (LP) is a chronic inflammatory mucocutaneous disease of unknown aetiology with an estimated incidence of 0.5%–4.0% having a female preponderance at a ratio of 1.5:1. Oral lichen planus (OLP) is commoner than the cutaneous form and tends to be more persistent and more refractory to the treatment. The prevalence of oral lichen planus in Indian population is around 3% with more female predilection. Oral lesions occur in 50%–70% of the patients with lichen planus. LP is considered to be a T-cell-mediated autoimmune skin disease, in which CD8+ cytotoxic T lymphocytes are major mediators. TNF-α and IL-10, interferon-gamma (IFN-γ), IL-4, and IL-8, have been suggested to have an important role in the pathogenesis of OLP. The complications of Lichen Planus include post-inflammatory hyperpigmentation, scarring alopecia, dyspareunia, oesophageal stenosis & possible malignant transformation. Mucocutaneous site biopsy can confirm the diagnosis when taken from the edge of a plaque. There is no cure for Lichen Planus, the management is often performed with the use of antihistamines, corticosteroids, retinoids, immunomodulators, phototherapy and immunosuppressives. Inconsistent results are shown by griseofulvin and chloroquine derivatives. (further prospective studies are needed).

Baricitinib as the first systemic treatment for severe alopecia areata

ABSTRACT Introduction Alopecia areata is a heterogenous, immune-mediated hair loss disorder that can affect any hair-bearing site on the body. Despite being one of the most prevalent autoimmune skin diseases, treatments have historically been limited to off-label medications that have demonstrated limited efficacy, especially in more severe forms of disease. Thus, there has long been an unmet need for rigorously studied therapeutics in alopecia areata. Areas covered Janus kinase inhibitors have proven to be an effective class of drugs for treating several inflammatory disorders. One such drug, baricitinib, has recently demonstrated significant hair regrowth in phase 2 and 3 alopecia areata trials. It has since become the first systemic therapy approved for treating severe alopecia areata. This review examines the role of Janus kinase pathways in alopecia areata’s pathogenesis and the safety and efficacy of baricitinib for treating severe alopecia areata. Expert opinion The approval of baricitinib for treating severe alopecia areata marks a major milestone in the disease’s history. While baricitinib has proven to be efficacious for this indication and has demonstrated an overall good safety profile, patients’ individual risk factors for serious adverse events should be assessed during shared decision-making with patients before initiating treatment.

Ayurvedic Management of Ek-Kushtha (Psoriasis): Review Article

Ek- Kustha is a kind of Kshudra Kushtha that resembles psoriasis in its clinical presentations and is primarily caused by an imbalance of the Vata and Kapha doshas. It bears a greater resemblance with Psoriasis, which is a long-lasting autoimmune and chronic inflammatory skin disorder clinically characterized by erythematous, sharply demarcated papules and rounded plaques, covered by silvery micaceous scale predominantly affecting the skin of elbows, knees, gluteal cleft, and scalp. Some people may have severe Psoriasis is involving their entire body. The quality of life of patient with Psoriasis is often diminished because of the appearance of skin. The mainstays of psoriasis treatment include immune system suppressing drugs like methotrexate, PUVA, vitamin D3 lotion, and steroid creams. Some contemporary therapeutic methods do have serious drawbacks, particularly when used for an extended period of time. These modern treatment modalities are not devoid from grave complications mainly in long term use. Owing to these reasons, there is a need for treatment having good efficacy and no toxicity profile. So this case study was conducted considering Psoriasis as Ek-kuhstha and Ayurvedic management was planned accordingly. Drastic results were witnessed by Shodhana (Vasantik Vaman & Shardik Virechana) and Shamana (Some internal herbo-mineral preparations, External oil application).

Evaluation of serum vitamin D concentration and blood eosinophil and basophil counts in patients with vitiligo: cross-sectional study from Rafsanjan and Zarand, Iran

Objective: Vitiligo is a chronic autoimmune depigmenting skin disorder. In this disease, the destruction of functional melanocytes can lead to reduced or absent pigmentation of the skin. Vitamin D deficiency has been reported in some autoimmune diseases. The association of eosinophils and basophils with autoimmune diseases has also been recently examined. Methods: The present study was performed to evaluate the serum vitamin D concentration and blood eosinophil and basophil counts in patients with vitiligo. Results: This descriptive cross-sectional study involved 30 patients with vitiligo. The average serum vitamin D concentration was significantly lower in the case group than in the control group (P = 0.01). Furthermore, the mean serum vitamin D concentration was significantly lower in women than in men (P = 0.03). The average eosinophil and basophil counts were not significantly different between the case and control groups. Discussion: The results of this study showed that the serum vitamin D concentration is low in patients with vitiligo. However, whether this reduction is a factor in the promotion of vitiligo or occurs after the onset of vitiligo remains unknown. Further studies on the serum vitamin D concentration in patients with vitiligo are needed to clarity this issue and develop effective treatments.

The effect of autoimmune skin disorders on post-operative outcomes following arthroplasty

IntroductionThe impact of autoimmune skin disorders on post-operative outcomes after TJA is conflicting and studies are limited by small sample sizes. The purpose of this study is to analyze a range of common autoimmune skin disorders and identify whether an increased risk of post-operative complication exists after total joint arthroplasty. MethodsData was collected from NIS database for patients diagnosed with autoimmune skin disorder (psoriasis, lupus, scleroderma, atopic dermatitis) and who underwent total hip arthroplasty (THA), total knee arthroplasty (TKA), or other TJA (shoulder elbow, wrist, ankle) between 2016 and 2019. Demographic, social, and comorbidity data was collected. Multivariate regression analyses were performed to assess the independent influence of autoimmune skin disorder on each post-operative outcome including implant infection, transfusion, revision, length of stay, cost, and mortality. ResultsAmong 55,755 patients with autoimmune skin disease who underwent TJA, psoriasis was associated with increased risk of periprosthetic joint infection following THA (odds ratio 2.44 [1.89–3.15]) and increased risk of transfusion following TKA (odds ratio 1.33 [1.076–1.64]). Similar analyses were performed for systemic lupus erythematosus, atopic dermatitis, and scleroderma, however no statistically significant associations were observed in any of the six collected post-operative outcomes. ConclusionThis study suggests psoriasis is an independent risk factor for poorer post-operative outcomes following total joint arthroplasty, however similar risk was not observed for other autoimmune skin disorders such as lupus, atopic dermatitis, or scleroderma.

Expression Signature of Immune-Related MicroRNAs in Autoimmune Skin Disease: Psoriasis and Vitiligo Insights.

Psoriasis and vitiligo are both chronic, skin-specific diseases classified as autoimmune diseases due to the involvement of several biochemical pathways in their pathogenesis, similar to those altered in other autoimmune diseases. The role of miRNAs in regulating skin autoimmune function has yet to be fully characterized. The aim of this study was to assess the expression profile of a panel of 11 circulating immune-related miRNAs in patients with autoimmune skin diseases, specifically psoriasis and vitiligo, and correlate their expression signature with the clinicopathological features of the diseases. Relative gene expression quantification for 11 immune-related circulating miRNAs in plasma was done for 300 subjects-100 patients with psoriasis, 100 patients with vitiligo and 100 normal healthy volunteers-followed by different modalities of bioinformatics analysis for the results. The expression levels of all the studied immune-related miRNAs were elevated in both autoimmune skin disorders, with much higher levels of expression in psoriasis than in vitiligo patients. There was a significant correlation between most of the studied miRNAs, suggesting shared target genes and/or pathways. Moreover, all the studied miRNAs showed significant results as biomarkers for autoimmune skin disease, with miRNA-145 being the best candidate. Regarding the clinicopathological data, miRNA-7, miRNA-9, miRNA-145, miRNA-148a, and miRNA-148b were positively correlated with age. All the miRNAs were inversely correlated with obesity and disease duration. This study highlights the critical role of miRNAs in skin-specific autoimmune diseases that proved to be potential biomarkers for autoimmune skin disorders, warranting their exploration as therapeutic targets.

Galectin-1 in Psoriatic arthritis, Psoriasis, Rheumatoid arthritis and its relation with disease activity and skin lesion

Immune mediated inflammatory diseases (IMIDs) are a diverse range of diseases that affect joints with early overlapping symptoms. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are the most common disorders sharing immune-pathogenic mechanisms that cause peripheral arthritis. Psoriasis (Ps) is a chronic inflammatory autoimmune skin disease characterized by epidermal hyperplasia with significant invasion by inflammatory cells. New biomarkers are required to enable an early diagnosis and differentiation between different types of IMIDs. In autoimmune disorders, galectin 1 (Gal-1) is a recognized as negative immune system regulator. This study aimed to determine the possibility of using gal-1 as a diagnostic marker to differentiate between RA and PsA with polyarthritis pattern, and between PsA and Ps, and to assess its relationship with disease activity and with skin lesion. In this case-control study included 40 PsA patients with polyarthritis pattern, 40 psoriatic patients, 40 RA patients and 20 normal controls. Gal-1 levels were measured in serum and skin biopsy and disease Activity Score (DAS-ESR) was assessed. Serum gal-1 level was significantly higher in RA group in comparison to PsA, psoriatic and control. In addition, compared to the normal group, psoriatic skin lesions from PsA and Ps patients had lower levels of gal-1. Serum gal-1 levels in the RA group did not correlate with other factors such as age, disease duration, deformity, extra-articular symptoms, or DAS-ESR. Furthermore, there was no correlation between the skin's level of gal-1 and psoriatic area and severity index (PASI) score, body surface area (BSA). In conclusion, serum Gal-1 concentration may serve as a diagnostic biomarker to distinguish between RA and PsA. However, it cannot assess activity or severity of RA, and cannot differentiate psoriatic lesion either from only Ps or PsA.

MiR-149-5p inhibits cell proliferation, promotes cell apoptosis and retards cell cycle of IL-22-stimulated HaCaT and NHEK keratinocytes via regulating PDE4D.

Psoriasis is a chronic autoimmune skin disease with unclear pathogenesis. It was found that miR-149-5p was significantly decreased in psoriatic lesion tissues. In this study, we aims to investigate the role and related molecular mechanism of miR-149-5p on psoriasis. IL-22 was used to stimulate HaCaT and NHEK cells to establish psoriasis model in vitro. The miR-149-5p and phosphodiesterase 4D (PDE4D) expression levels were detected by quantitative real-time PCR. HaCaT and NHEK cells proliferation was determined by Cell Couting Kit-8 assay. The cell apoptosis and cell cycle were detected by flow cytometry. The cleaved Caspase-3, Bax and Bcl-2 protein expressions were detected by western blot. The targeting relationship between PDE4D and miR-149-5p was predicted and confirmed by Starbase V2.0 and dual-luciferase reporter assay, respectively. There was a low expression level of miR-149-5p and a high expression of PDE4D in psoriatic lesion tissues. MiR-149-5p could target PDE4D. IL-22 promoted HaCaT and NHEK cells proliferation, while inhibited cell apoptosis and accelerated cell cycle. Moreover, IL-22 decreased the expressions of cleaved Caspase-3 and Bax, and increased the expression of Bcl-2. And the overexpressed miR-149-5p promoted HaCaT and NHEK cells apoptosis, inhibited cell proliferation and retarded cell cycle, meanwhile increased the cleaved Caspase-3 and Bax expressions, decreased the Bcl-2 expression. In addition, PDE4D overexpression has the opposite effect as miR-149-5p. The overexpressed miR-149-5p inhibits IL-22-stimulated HaCaT and NHEK keratinocytes proliferation, promotes cell apoptosis and retards cell cycle by down-regulating the expression of PDE4D, which could be the promising therapeutic target of psoriasis.

Serum levels of ifn-γ, complement component c3 c4 and vitamin d3 in the prognosis of patients with alopecia areata prospective teachers

Alopecia areata is a prevalent autoimmune skin disorder. The current investigation aims to evolve the function of serum IFN-, complement component C3 C4, and vitamin D3 levels in the prognosis of patients with alopecia areata. The blood sample was taken from twenty AA patients and twenty healthy controls. Interferon (IFN-) levels in serum were evaluated using the ELISA method, V.D3 was detected using the Roche electrochemiluminescence method, and C3 and C4 were detected using the immunoturbidimetry method. . In the current study observed elevated levels of IFN-γ (299±115.7 Pg/ml), while the control group was lowest 73±10.84 Pg/ml .This funding was highly significantly different (p-value 0.00). The Mean±SD Level of components C3 and C4 in the current study were (1.37±0.903) (0.29±0.029) Alopecia Areata cases were not statistically different from the usual range, however vitamin D3 levels were severely deficient. (6.86±4.03) when compared to normal range. Distribution of AA among male was highly observed in age group NO = 10 (50%) 1 - 19years follow by age group NO = 4(20%) 20-39 and (40-50) respectively while Alopecia Areata among females was the lowest distribution.

The Free Sign in morphea and other sclerosing disorders: A clue to the presence of early sclerosis?

The Floating Sign is a histopathologic clue to the diagnosis of autoimmune sclerosing skin disorders such as morphea and interstitial granulomatous dermatitis (IGD). On the other hand, the "free-floating" sign has been associated with neoplasms, for example, dermatofibroma and interstitial mycosis fungoides. Herein, we report the Free Sign in sclerosing skin disorders. In a case-control study, we applied detailed histopathologic definitions of Floating Sign and Free Sign to assess their presence in morphea, IGD, and other sclerosing disorders. Free Sign was present in most cases of morphea (46/55, 84%) and IGD (7/13, 54%) but not necrobiosis lipoidica (NL) (6/14, 42.8%) or sclerodermoid graft versus host disease (SGVHD) (2/7, 28.5%). The sensitivity and specificity of Free Sign for morphea versus other disorders was 84% and 56%, respectively. Floating Sign was not identified in most cases: NL (3/14, 21.4%), SGVHD (1/7, 14.2%), morphea (5/55, 9%), IGD (1/13, 7.7%). The diagnostic sensitivity of Floating Sign in morphea was 9%. The Free Sign was present in most cases of morphea in our series and may represent a clue to the presence of evolving sclerosis. Free Sign may be seen in other sclerosing disorders. Technical artifact is a potential cause of a false-positive Free Sign.

Risk of skin cancers in mycosis fungoides patients receiving PUVA therapy: A real-life experience from a single tertiary center.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Skin-directed therapies, including phototherapy, are the first-line treatment modalities. Psoralen plus ultraviolet A light photochemotherapy (PUVA) is quite effective in controlling the disease; however, long-term adverse effects, particularly carcinogenesis, are the cons of this treatment. There are various studies on the negative impact of PUVA on skin cancer in patients with autoimmune skin diseases. The data on the long-term effects of phototherapy on MF patients are scarce. All MF cases that received PUVA alone or combined with other treatments at a single tertiary center were analyzed. This study compared the development of non-melanoma skin cancers, melanoma, and solid organ tumors in MF patients with at least 5-year follow-up data with age- and sex-matched controls. A total of 104 patients were included in the study. Ninety-two malignancies were detected in 16 (15.4%) patients, and six developed multiple malignancies. Skin cancers consisted of 56 basal cell carcinomas, 16 Bowen's disease, four squamous cell carcinomas, three melanomas, two basosquamous cell carcinomas, one Kaposi sarcoma, and one keratoacanthoma were found in nine (8.7%) patients. Eight patients developed three solid cancers and six lymphomas. The risk of developing skin cancer was associated with the total number of PUVA sessions (<250 vs ≥250 sessions; hazard ratio (HR) 4.44, 95% confidence interval (CI) 1.033-19.068; p = .045). 9 (13.2%) of 68 patients who had follow-ups for at least 5 years developed skin cancer. Compared to an age- and sex-matched cohort, the prevalence of new skin cancer was considerably greater (p = .009). Patients with MF are predisposed to develop secondary malignancies, and continual exposure to PUVA may potentiate this risk. Annual digital dermoscopic follow-up in MF patients treated with UVA is advised for early diagnosis and treatment of secondary cutaneous malignancies.

The Role of Oxidative Stress in Vitiligo: An Update on Its Pathogenesis and Therapeutic Implications.

Vitiligo is an autoimmune skin disorder caused by dysfunctional pigment-producing melanocytes which are attacked by immune cells. Oxidative stress is considered to play a crucial role in activating consequent autoimmune responses related to vitiligo. Melanin synthesis by melanocytes is the main intracellular stressor, producing reactive oxygen species (ROS). Under normal physiological conditions, the antioxidative nuclear factor erythroid 2-related factor 2 (Nrf2) pathway functions as a crucial mediator for cells to resist oxidative stress. In pathological situations, such as with antioxidant defects or under inflammation, ROS accumulate and cause cell damage. Herein, we summarize events at the cellular level under excessive ROS in vitiligo and highlight exposure to melanocyte-specific antigens that trigger immune responses. Such responses lead to functional impairment and the death of melanocytes, which sequentially increase melanocyte cytotoxicity through both innate and adaptive immunity. This report provides new perspectives and advances our understanding of interrelationships between oxidative stress and autoimmunity in the pathogenesis of vitiligo. We describe progress with targeted antioxidant therapy, with the aim of providing potential therapeutic approaches.

Mixed muco-cutaneous pemphigoid: Clinical and immunological features of 15 cases.

We describe a series of patients whose auto-immune bullous skin disease (AIBD) of the dermal-epidermal junction (DEJ) was characterized by clinical, immunological and ultrastructural features intermediate between bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP), and a recalcitrant course. From the database of the French reference centre for AIBD, we screened all the patients who were referred for an AIBD of the DEJ with a mucosal involvement, who neither met the diagnostic criteria for the diagnosis of BP, nor were typical of MMP. Sera were analysed by NC16A-ELISA and immunobloting against the C-terminal and LAD-1 parts of BP180. Skin biopsies were studied by direct immunoelectron microscopy (IEM). Fifteen patients (4 males, 11 females) of mean age 70.8 ± 11.8 years were included. The mucosal involvement was localized in oral cavity in all cases and in pharyngeal/laryngeal or genital area in 8 (53%), and 6 patients (40%), respectively. No patient had ocular involvement, nor atrophic or fibrosing scars. All patients had extensive skin lesions (mean BPDAI score =65.9 ± 24.4), which predominated on the upper body part. Direct IEM performed on 8 patients showed IgG deposits on the lamina lucida in all cases, and the lamina densa in 5 cases. All sera recognized NC16A, while none recognized BP-230 in ELISA. 10 out of the 13 tested sera (76.9%) contained IgG which recognized the C-terminal domain of BP180 and 10 sera (76.9%) the LAD-1 domain of BP180. Patients poorly responded to super potent topical corticosteroids and were treated with oral corticosteroids ± immunosuppressant in 13 cases (86.6%). This mixed muco-cutaneous pemphigoid differs from BP by the younger age of patients, multiple mucosae involvement, circulating antibodies against both the C- and N-terminal part of BP180, and very poor response to topical CS. It differs from MMP by extensive inflammatory skin lesions, absence of ocular involvement and atrophic/fibrosing scars.

Interleukin-21 in autoimmune and inflammatory skin diseases.

Studies on the role of interleukins (ILs) in autoimmune and inflammatory diseases allow for the better understanding of pathologic mechanisms of disease and reshaping of treatment modalities. The development of monoclonal antibodies targeting specific ILs or IL signaling pathways (i.e., anti-IL-17/IL-23 in psoriasis or anti-IL-4/IL-13 in atopic dermatitis) is the shining example of therapeutic interventions in research. IL-21, belonging to the group of ɣc-cytokines (IL-2, IL-4, IL-7, IL-9, and IL-15), is gaining attention for its pleiotropic role in several types of immune cells as activator of various inflammatory pathways. In both health and disease, IL-21 sustains T- and B-cell activity. Together with IL-6, IL-21 helps to generate Th17 cells, promotes CXCR5 expression in T cells, and their maturation into follicular T helper cells. In B cells, IL-21 sustains their proliferation and maturation into plasma cells and promotes class switching and antigen-specific antibody production. Due to these characteristics, IL-21 is a main factor in numerous immunologic disorders, such as rheumatoid arthritis and MS. Studies in preclinical skin disease models and on human skin strongly suggest that IL-21 is crucially involved in inflammatory and autoimmune cutaneous disorders. Here, we summarize the current knowledge of IL-21 in well-known skin diseases.

Dermoscopy of granulomatous and autoimmune skin diseases

Dermoscopy is an easily accessible, noninvasive diagnostic tool, originally used in the differentiation of benign and malignant skin tumors. Other structures beside pigment content observed by dermoscopy, e.g., scaling, follicles, or vessels, may present in aspecific pattern in different dermatoses. Recognition of these patterns may aid the diagnosis of inflammatory and infectious dermatological conditions. The aim of this article is to review the distinct dermoscopic features of granulomatous and autoimmune skin diseases. Diagnosis of granulomatous skin disorders is based on the histopathological examination. The dermoscopic picture of these diseases (cutaneous sarcoidosis, granuloma annulare, necrobiosis lipoidica, and granulomatous rosacea) show many similarities; however, there are some differences to note between the dermatoses, mainly in granuloma annulare. The cornerstones of the diagnostic process of autoimmune skin diseases (morphea, systemic sclerosis, dermatomyositis, cutaneous lupus erythematosus) include the clinical picture, immunoserology, and histology; however, dermoscopy may aid the diagnostic process and follow-up of the patients. For those diseases, where vascular abnormalities play an important role in the pathogenesis, videocapillaroscopy is used for examination of the microcirculation at the nailfold capillaries. Dermoscopy can be an easy-to-use everyday diagnostic tool in clinical practice regarding granulomatous and autoimmune skin diseases. Although punch biopsy is inevitable in many cases, the distinct dermoscopic structures can aid the diagnostic process.

The First Live-Cell Based Product in The Iranian Drug List; ReColorCell®.

Vitiligo is an autoimmune skin disorder that can significantly affect the quality of life in patients. However, current treatment strategies such as phototherapy, topical glucocorticosteroids, or systemic immunosuppressants can be helpful in vitiligo management, and treatments for disease stability which is the main challenge in vitiligo management. Novel therapeutic modalities have made promising advances in this regard. Molecular targeted therapy to target Janus-activated kinase (JAK) such as Tofacitinib and Ruxolitinib in addition to the cell-based treatments are innovative therapeutic options, which are recently used for vitiligo treatment. Transplantation of non-cultured melanocytes-keratinocytes have been studied in Iran and phase one data published in 2010 on 10 patients that continued on 300 patients as phase three in 2018. Cell Tech Pharmed™ Co. registered and applied this cell-based product, ReColorCell®, as a GMP certified by Iranian Food and Drug Administration (IR-FDA). On 11th December 2021, ReColorCell® officially registered as the first cell-based product in the Iranian drug list (IDL). Currently, the post-market study of this product is ongoing.