Risk factors for cardiovascular diseases in patients with vitiligo: an analysis of current evidence.

OBJECTIVE: The relationship between vitiligo and cardiovascular diseases remains controversial. This study aimed to systematically review the evidence comparing cardiovascular disease risk factors between patients with vitiligo and controls and to perform a meta-analysis of the results. DATA SOURCES: A comprehensive database search was performed for all studies in PubMed, EMBASE, and Cochrane Central Register databases from inception to November, 2023. The main keywords used were vitiligo, hypertension, diabetes, hyperlipidemia, metabolic syndrome, obesity, smoking, alcohol consumption, C-reactive protein, and homocysteine. STUDY SELECTION: Only observational studies and no randomized controlled trials were included. Of the 1269 studies initially selected, the full texts of 108 were assessed for eligibility, and 74 were ultimately included in the analysis. DATA EXTRACTION AND SYNTHESIS: Three reviewers independently extracted the following data: study design, number and characteristics of participants, inclusion indicators, and disease duration. A meta-analysis of the single-group rates was performed for the diabetes, hypertension, hyperlipidemia, and obesity groups. Random-effects or fixed-effects models were used to calculate the sample-size weighted averages for the indicators included in the studies. MAIN OUTCOMES AND MEASURES: The primary outcomes were co-morbidity analysis and co-morbidity rates of vitiligo with metabolic syndrome, obesity, hyperlipidemia, hypertension, and diabetes mellitus. Secondary outcomes were factors associated with vitiligo and cardiovascular disease. RESULTS: This meta-analysis concluded that comorbidities in patients with vitiligo included metabolic syndrome, diabetes, obesity, hyperlipidemia, and hypertension, with comorbidity rates of 28.3%, 6.0%, 38.5%, 43.0%, and 15.8%, respectively. Simultaneously, we showed that the vitiligo group differed significantly from the control group in the following aspects: fasting blood glucose, insulin, systolic and diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, homocysteine, C-reactive protein, smoking, and alcohol consumption. However, no significant differences were observed between the vitiligo and control groups in terms of waist circumference, body mass index, or phospholipid levels. LIMITATIONS: The vast majority of the studies were from Eastern countries; therefore, extrapolation of these results to Western populations is questionable. The significant heterogeneity may be due to different protocols, doses, durations, center settings, population registries, etc., which severely compromise the validity of the results. CONCLUSION: This study summarized not only the factors associated with, but also those not associated with, cardiovascular disease in patients with vitiligo. This study provides a foundation for the prevention and treatment of cardiovascular disease in patients with vitiligo.

The relationship between vitiligo and cardiovascular diseases remains controversial.This meta-analysis concluded that comorbidities in patients with vitiligo include metabolic syndrome, diabetes, obesity, hyperlipidemia, and hypertension, with comorbidity rates of 28.3%, 6.0%, 38.5%, 43.0%, and 15.8%.Our study identified cardiovascular disease risk factors in patients with vitiligo, including smoking, alcohol consumption, high serum SBP, DBP, FBG, CRP, TC, TG, LDL, insulin, and Hcy, and low serum HDL levels.

Actinic keratoses and squamous cell carcinoma limited to photo-exposed skin in vitiligo vulgaris in pigmented skin type.

Vitiligo skin has a lesser number of photoprotective melanocytes-theoretically, there is a higher risk of development of non-melanoma skin cancers in such patients. But most studies in Caucasian patients have shown decreased incidence of non-melanoma skin cancers in patients with vitiligo. In Indian patients, there is a paucity of literature on such adverse events. We report a case of actinic keratoses, cutaneous horn with dysplasia and squamous cell carcinoma developing exclusively over photo-exposed vitiligo lesions in an Indian woman in her 60s (housewife, Fitzpatrick skin type V and average daily photo-exposure time 2-4 hours) of long-standing vitiligo vulgaris without any history of phototherapy. The photoprotected lesional skin was completely normal with no clinically appreciable enlarged regional lymph nodes. Shave and elliptical excision of the suspicious lesions were done, and histopathology showed various degrees of malignant transformation in various lesions. The patient was started on topical imiquimod for the lesions of actinic keratoses and was referred for staging and wide excision of squamous cell carcinoma lesion. We report this case for its rarity and to emphasise the fact that there is a need for counselling for lifestyle modification in patients with vitiligo as the use of sunscreens is often not practised by Indian patients due to financial constraints and physical measures such as using full sleeves, high-collared dresses and scarves should be encouraged.

The Risk of Keratinocyte Cancer in Vitiligo and the Potential Mechanisms Involved.

Although light skin types are associated with increased skin cancer risk, a lower incidence of both melanoma and nonmelanoma skin cancer (NMSC) has been reported in patients with vitiligo. We performed a systematic review and meta-analysis on the NMSC risk in patients with vitiligo, indicating a reduced relative risk ratio of NMSC in vitiligo. Furthermore, we propose a series of hypotheses on the underlying mechanisms, including both immune-mediated and nonimmune-mediated pathways. This study reveals insights into the relationship between vitiligo and keratinocyte cancer and can also be used to better inform patients with vitiligo.

All-Cause and Cause-Specific Mortality among Patients with Vitiligo: A Nationwide Population-Based Study in Korea.

Vitiligo is a common autoimmune skin disorder; however, there is limited information about risks of mortality among patients with vitiligo. Therefore, we aimed to investigate the mortality in patients with vitiligo. A population-based cohort study was conducted using the data linkage of the National Health Insurance Service database and the National Death Registry. Patients with incident vitiligo were matched with sociodemographic factors-matched controls without vitiligo in a 1:5 ratio. All-cause and cause-specific mortalities were compared between patients with vitiligo and controls. In total, 107,424 patients with incident vitiligo and 537,120 matched controls were included. The mortality rates were 34.8 and 45.3 per 10,000 person-years in patients and controls, respectively. Patients with vitiligo showed a significantly lower risk of mortality (adjusted hazard ratio = 0.75, 95% confidence interval = 0.72-0.78). The cause-specific mortality from infectious diseases, oncologic diseases, hematologic diseases, endocrine diseases, neurologic diseases, cardiovascular diseases, respiratory diseases, and renal/urogenital disease was significantly lower in patients with vitiligo. Patients with vitiligo were associated with a lower risk of mortality, suggesting that vitiligo-associated autoimmunity might contribute to reduced morbidity and mortality.

Association Between Eight Autoimmune Diseases and Thyroid Cancer: A Nationwide Cohort Study.

Background: It has often been reported that thyroid-specific autoimmune diseases (ADs), such as Hashimoto's thyroiditis and Graves' disease, could increase the risk of thyroid cancer, but the association between other ADs beyond thyroid and thyroid cancer has not been well investigated. This study aimed to examine the risk of thyroid cancer in patients with eight ADs compared with those without ADs. Methods: This nationwide retrospective matched cohort study was conducted to investigate the relationship of eight ADs (Hashimoto's thyroiditis, Graves' disease, type 1 diabetes mellitus, Sjogren's disease, inflammatory bowel disease [IBD], vitiligo, systemic lupus erythematosus, and rheumatoid arthritis [RA]) with the risk of incident thyroid cancer using the National Health Insurance Service-National Sample Cohort. The Cox-proportional hazard model was used to estimate the adjusted hazard ratio (HR) and confidence intervals (CI) for thyroid cancer in relation to each of AD compared with control group without AD. Results: During the average follow-up of 9.49 years, 138 thyroid cancer cases were newly developed in control group and 268 cases were occurred in group with 8 ADs. For all of study participants, the risk of thyroid cancer was significantly increased in patients with Hashimoto's thyroiditis (HR = 2.10 [1.57-2.81]), Graves' disease (HR = 2.67 [1.99-3.62]), IBD (HR = 2.06 [1.50-2.83]), vitiligo (HR = 1.71 [1.13-2.59]), RA (HR = 1.76 [1.07-2.90]), and total of 8 ADs (HR = 1.97 [1.60-2.42]) compared with control group without ADs. When ADs were divided into three types, thyroid-specific ADs (HR = 2.37 [1.85-3.03]) showed the strongest and significant association with thyroid cancer, followed by local ADs (HR = 1.83 [1.41-2.38]), and systemic ADs (HR = 1.77 [1.14-2.74]). Conclusions: Specific ADs-especially for thyroid-specific AD, vitiligo, IBD, and RA-were associated with increased risk for thyroid cancer.

Atypical herpes zoster ophthalmicus with madarosis of upper eyelid, recurrent iridocyclitis and atrophic multifocal chorioretinopathy.

INTRODUCTION: Ocular involvement due to varicella-zoster virus (VZV) infection includes conjunctivitis, scleritis, keratitis, uveitis, and necrotizing retinitis. Non-necrotizing chorioretinopathy as a late manifestation has been described. CASE REPORT: A 50-year-old immunocompetent man developed herpes zoster ophthalmicus (HZO) in the right V1 dermatome with acute anterior uveitis (AAU) treated with oral valaciclovir and topical steroid and a chalazion in the upper eyelid with associated madarosis. Four months later, he presented recurrence of the AAU and multiple areas of chorioretinal atrophy on fundoscopy. Biopsy of the upper eyelid lesion revealed granulomatous inflammation of the eyelid margin and polymerase chain reaction study (PCR) tested positive for VZV-specific DNA. The iridocyclitis was resolved with oral valaciclovir at maximum doses with minimal choroidal pigmentary changes. DISCUSSION: VZV ophthalmic infection starts by reactivation from the trigeminal ganglion, and it spreads to the isthmus of the pilosebaceous follicles and the epidermis, which can cause involvement of follicle and sebaceous glands. Chorioretinopathy is a rare form of late-onset non-necrotizing herpetic uveitis characterized by atrophic-appearing hypopigmented lesions, the pathogenesis of which is unknown. A direct viral infection or secondary to occlusive choroidal vasculitis is postulated at the level of the choriocapillaris and more recently it has been referred to as "choroidal vitiligo" due to possible involvement of choroidal melanocytes, as occurs in cases of cutaneous vitiligo due to VZV infection.

Vitiligo and Crohn's disease form an autoimmune cluster: insights from a population-based study.

BACKGROUND: While the coexistence of vitiligo and Crohn's disease (CD) has been reported in individual patients, the epidemiological association between these autoimmune conditions remains inconclusive. OBJECTIVE: To assess the bidirectional association between vitiligo and CD. METHODS: A population-based study was performed to compare vitiligo patients (n = 20,851) with age-, sex- and ethnicity-matched control subjects (n = 102,475) regarding the incidence of new-onset and the prevalence of preexisting CD. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by multivariable Cox regression and logistic regression, respectively. RESULTS: The incidence rate of new-onset CD was evaluated at 3.6 (95% CI, 2.7-4.9) cases per 10,000 person-years (PY) in patients with vitiligo and 2.4 (95% CI, 2.0-2.9) cases per 10,000 PY in controls. Patients with vitiligo experienced an elevated risk of CD (fully adjusted HR, 1.60; 95% CI, 1.10-2.34; p = 0.015). Congruently, a history of preexisting CD predicted elevated odds of having subsequent vitiligo (fully adjusted OR, 1.49; 95% CI, 1.15-1.93; p = 0.002). Compared to other patients with vitiligo, those with vitiligo and comorbid CD were older and had a higher prevalence of diabetes mellitus, hyperlipidemia, and hypertension but a comparable all-cause mortality rate. CONCLUSIONS: The current study depicts a robust bidirectional association between vitiligo and CD. This knowledge is of clinical implication for physicians managing patients with both conditions. The diagnostic threshold for CD should be lowered in vitiligo patients with compatible symptoms.

Vitiligo as a First Sign of Vogt-Koyanagi-Harada Disease.

Vogt-Koyanagi-Harada (VKH) disease is a multisystem disorder characterized by bilateral granulomatous panuveitis resulting in serous retinal detachments, disk edema, and a sunset glow fundus development. Furthermore, it is associated with various extraocular findings, such as tinnitus, hearing loss, vertigo, poliosis, and vitiligo (1). VKH is considered to be an autoimmune disease mediated by T-cells targeting melanocyte antigen tyrosinase peptide (2). Moreover, VKH more often occurs in individuals with a genetic predisposition to the disease, including those of Asian and Hispanic heritage (3). Three disease categories have been recognized, including complete, incomplete, and probable VKH. Each category has different clinical features, varying from neurological and auditory manifestations to ophthalmologic and dermatologic findings (1). Herein, we present a case of chronic complete Vogt-Koyanagi-Harada disease, which started with vitiligo. CASE REPORT A forty-year-old female patient presented to the Department of Ophthalmology with photophobia, dull eye pain, and a gradual decrease in visual acuity over two months. In addition, at clinical examination, vitiligo spots were observed on the patient's hands and the periocular area. The patient's medical history revealed she had vitiligo from a young age. Additionally, she developed generalized epilepsy and headaches in adolescence. The neurologic symptoms had been treated, whereas dermatologic workup and treatment were never performed. It was also found that our patient was of Hispanic heritage, which later helped establish a diagnosis. Ophthalmologic examination revealed eye redness, hypotony, keratic precipitates, anterior chamber cells, and posterior synechiaes. Fundoscopy showed mild vitreous haze, optic disc and macular edema, chorioretinal thickening (also seen on eye ultrasound), and disturbance of retinal pigment epithelium (Figure 1). A standard diagnostic protocol for uveitis was performed. Serology for infectious causes was performed, and IgG for CMV and HSV 1 were positive. Tuberculosis testing was negative. HLA testing showed positive HLA-DR1, HLA B13/18, and HLA DQ-1 antigens. There were no cells in the intraocular fluid, and PCR of the fluid was negative for CMV and HSV 1 and 2. Considering the noninfectious uveitis, a history of neurological and dermatological disorders, and the Hispanic heritage of our patient, the diagnosis of Vogt-Koyanagi-Harada disease was established. Systemic methylprednisone in a 1.5 mg/kg dose was introduced during the first hospitalization. After slow tapering of the corticosteroid therapy, cyclosporine A in a 175 mg/day dose and azathioprine in a 100 mg/day dose were introduced for prolonged therapy. Although signs of eye inflammation were reduced, poor prognostic signs such as hypotony and optic disc edema were persistent. Therefore, the TNF-α inhibitor adalimumab was introduced. After the introduction of adalimumab, the disease was considered stable with no worsening of visual function, but vitiligo spots continued to progress (Figure 2). DISCUSSION Our case presents a chronic stage Vogt-Koyanagi-Harada disease in a person with a Hispanic heritage. VKH is a rare autoimmune disease that involves multiple organ systems, including the eyes, skin, and auditory and neurological systems. In the pathogenesis of the disease, there is an underlying granulomatous inflammation mediated by T-lymphocytes targeting melanocyte-specific antigens (4). Besides the immune response, genetics is an integral part of the etiology of the disease. HLA-DR1 and HLA-DR4 have been associated with VKH disease, specifically in the Hispanic and Asian populations (3,5). Other studies have found that VKH is more common in people of Asian and Hispanic heritage than in Caucasian or African-American individuals (6). In our case report, the Hispanic origin of our patient was essential for the diagnosis of the disease. There are four phases of VKH disease. The prodromal phase lasts a few days to a few weeks and is characterized by extraocular findings such as headache, vertigo, meningismus, and nausea (1). After the prodromal phase, the acute uveitic phase occurs, with sudden onset of blurred vision, conjunctival injection, and photophobia (1,7). Weeks to months after, the convalescent phase occurs, with signs of depigmentation such as vitiligo, poliosis, and vitiligo in the ocular limbal area, called the Sugiura sign. Finally, six to nine months after initial symptoms, the chronic recurrent phase occurs, leading to exacerbations of anterior uveitis (1). Even though most patients develop skin changes in the convalescent phase, our patients experienced skin depigmentation years before ocular involvement. VKH can be complete, incomplete, or probable. Our patient is an example of complete VKH, since she fulfilled all criteria for complete VKH, including 1) no history of penetrating ocular trauma or surgery, 2) no clinical or laboratory evidence of other ocular diseases, 3) bilateral ocular involvement, 4) neurological findings, and 5) integumentary findings (8). Treatment for VKH consists of high-dose systemic corticosteroids, administered orally or through intravenous delivery, followed by slow tapering of oral corticosteroids. Immunosuppressive therapy with cyclosporine and/or azathioprine is considered if the symptoms are persistent or worsening. In case of no improvement, biological agents such as infliximab and adalimumab are included (4).

The time window for the reversal of depigmentation from aggravation to recovery in a non-small-cell lung cancer patient with pre-existing vitiligo using anti-programmed cell death-1 therapy: A case report.

Immune checkpoint inhibitors have made remarkable breakthroughs in the treatment of lung cancer, bringing significant survival benefits to the patients. A number of adverse events aggravated by immunotherapy in patients with pre-existing autoimmune diseases have been reported in the past, especially skin toxicity, such as rash, pruritus, erythema, and vitiligo. However, whether the exacerbated autoimmune disease is reversible and when it will return to its original state after immunotherapy discontinuation is still inconclusive. In our report, we described a patient diagnosed with non-small cell lung cancer whose vitiligo was stable for about 10 years. We followed up and observed the patient's skin depigmentation for the complete time window, from aggravation of application anti-programmed cell death-1 receptor antibody (anti-PD-1 antibody) to recovery after the withdrawal. We presented the objective images at particular time points using reflectance confocal microscopy and wood's light. We found that the use of anti-PD-1 antibody aggravated in skin toxicity, but it was reversible, the time window from the beginning to recovery status was approximately 9 months. We used this real case scenario to explain the relationships between immunotherapy and autoimmune diseases.

Fenómeno infrecuente la co-localización de alopecia frontal fibrosante y vitiligo en un varón: informe de un caso / Infrequent phenomenon the co-localization of fibrosing frontal alopecia and vitiligo in a male: case repor

La alopecia frontal fibrosante es una alopecia cicatricial que se caracteriza por la recesión de la línea de implantación frontotemporal que afecta principalmente a mujeres caucásicas en edad posmenopáusica y rara vez a hombres. Actualmente los mecanismos específicos de desarrollo continúan en estudio; sin embargo hay varias hipótesis sobre la asociación de la alopecia frontal fibrosante con otros trastornos autoinmunitarios. Se comunica el caso de un paciente masculino de 58 años con alopecia frontal fibrosante en áreas comprometidas por vitiligo. (AU)

Frontal fibrosing alopecia is a cicatricial alopecic characterized by progressive regression of the frontotemporal hairline. It usually affects postmenopausal caucasian women, and rarely men. Currently the specific mechanisms of development remain unknown, however there are several hypotheses about the association of frontal fibrosing alopecia with other autoimmune disorders. The case of a 58-year-old male patient with frontal fibrosing alopecia in areas affected by vitiligo. (AU)

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study.

Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]025 > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC025 = 4.87), bullous pemphigoid (IC025 = 4.08), lichenoid dermatitis (IC025 = 3.69), erythema multiforme (IC025 = 1.03), toxic epidermal necrolysis (IC025 = 0.95), Stevens‒Johnson syndrome (IC025 = 0.41), drug eruption (IC025 = 0.11), and eczematous dermatitis (IC025 = 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.

Eruptive facial lentiginosis-like repigmentation in a patient with longstanding generalized vitiligo without a detectable trigger.

Spontaneous appearance of hyperpigmented macules on chronic vitiligo lesions is a very rare phenomenon, which is described as eruptive lentiginosis. We describe the case of a patient with chronic non-segmental generalized vitiligo who presented with a sudden onset of hyperpigmented macules on depigmented areas of the face. A biopsy showed pigmented basal keratinocytes in the interfollicular epidermis, and immunohisochemistry with anti-SOX10 antibodies showed nuclei of single melanocytes. This case shows that even long-standing depigmented vitiligo lesions may contain functional melanocytes or their precursors.

[Eosinophilic duodenitis associated to food allergy debuting as acute visceral pain in an adult with vitiligo: a case report]. / Duodenitis eosinofílica asociada a alergia alimentaria debutando como dolor visceral agudo en un adulto con vitíligo: reporte de un caso.

BACKGROUND: Eosinophilic duodenitis has a prevalence of 5.1 to 8.2 per 100000 persons. The underlying molecular mechanisms are unknown, but hypersensitivity (seasonal and food allergies, asthma, eczema) response plays a major role in its pathogenesis, allergic predisposition can be found up-to 25-35% of cases. The diagnosis includes clinical manifestation, imaging findings and histological evidence of eosinophilic infiltration >20 eosinophils per high-power field. This is a clinical case report. a 25-years old man with vitiligo consult to emergency department referring dyspepsia symptoms, vomiting and abdominal pain of maximal intensity, in the medical exam upper abdominal pain was found, blood laboratories were unremarkable except a high net eosinophil-count >2000 cells/ul, abdominal ultrasound were normal, upper endoscopy revealed duodenitis with rigid and thickened folds, colonoscopy show hemorrhoids grade I. Coproscopy exam was negative for parasites, total IgE, IgA and IgG were in normal range, a positive IgG to Toxoplasma gondii was reported, autoimmunity panel was negative. In the following 4 days the abdominal pain and eosinophils count increase, a new abdomin-pelvic tomography was done showing thickened duodenum with a new endoscopy showing marked edema in duodenum with severe biliary reflux with biopsies describing an atrophic chronic duodenitis. Allergy tests -skin prick and patch tests- were done resulting positive to cereals (rye, soy, barley), Manihot esculenta, green banana, tomato, cow milk, orange and pineapple. A restrictive diet and protons pump inhibitor was indicated, ambulatory control at 45 days after show symptoms resolution with a normal blood eosinophils count. Here is reported a case of eosinophilic duodenitis related to food allergy in a young man with vitiligo debuting with an unusual clinical presentation of acute visceral pain and biliary reflux which resolved with elimination diet and pantoprazole without use of corticoids, with both, IgE and non-IgE mechanisms playing important roles explaining food sensitization.

Case Report: Severe Hypocalcemic Episodes Due to Autoimmune Enteropathy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic disorder, associated with endocrine deficiencies and non-endocrine involvement. Gastrointestinal (GI) manifestations appear in approximately 25% of patients and are the presenting symptom in about 10% of them. Limited awareness among pediatricians of autoimmune enteropathy (AIE) caused by destruction of the gut endocrine cells in APECED patients delays diagnosis and appropriate therapy. We describe an 18-year-old female presenting at the age of 6.10 years with hypoparathyroidism, oral candidiasis and vitiligo. The clinical diagnosis of APECED was confirmed by sequencing the autoimmune regulator-encoding (AIRE) gene. Several characteristics of the disease-Hashimoto's thyroiditis, Addison's disease, diabetes mellitus type 1 and primary ovarian insufficiency-developed over the years. She had recurrent episodes of severe intractable hypocalcemia. Extensive GI investigations for possible malabsorption, including laboratory analyses, imaging and endoscopy with biopsies were unremarkable. Revision of the biopsies and chromogranin A (CgA) immunostaining demonstrated complete loss of enteroendocrine cells in the duodenum and small intestine, confirming the diagnosis of AIE. Management of hypocalcemia was challenging. Only intravenous calcitriol maintained calcium in the normal range. Between hypocalcemic episodes, the proband maintained normal calcium levels, suggesting a fluctuating disease course. Repeated intestinal biopsy revealed positive intestinal CgA immunostaining. The attribution of severe hypocalcemic episodes to AIE emphasizes the need for increased awareness of this unique presentation of APECED. The fluctuating disease course and repeated intestinal biopsy showing positive CgA immunostaining support a reversible effect of GI involvement. CgA immunostaining is indicated in patients with APECED for whom all other investigations have failed to reveal an explanation for the malabsorption.

Vitiligo and chronic autoimmune thyroiditis.

Vitiligo, the discoloration of the skin, has different autoimmune mechanisms reflected by many biomarkers as shown by skin histology, staining for CD4 and CD8 T lymphocytes, chemokine ligand 9 or circulating cytokines such as interleukin (IL)-1 beta, interferon (IFN)-gamma, transforming growth factor (TGF)-beta, antibodies, markers of oxidative stress, chemokines, and others. In this narrative review, we aim to overview vitiligo in relationship with chronic autoimmune thyroiditis. Regarding vitiligo, more than 50 different genetic loci have been associated with this disease, and the heritability is high. There is a 20% risk of an environmental connection which may also act as a trigger; moreover, the association with human leukocyte antigen (HLA) expression is well recognized. The specific lesions display CD8+ tissue-resident memory T cells as continuous key activators of melanocytes. The association with chronic thyroiditis is based on common autoimmune background and excessive reactive oxygen species that destroy melanocytes and thyrocytes (oxidative stress hypothesis) with thyroxine and melanin as target molecules, thus sharing a common origin: tyrosine. Moreover, common epigenetic anomalies or mutations of the Forkhead transcription factor D3 (FOXD3) have been described. Since vitiligo affects up to 1-2% of the population worldwide and 34% of patients have positive thyroid antibodies, apart from common autoimmunity background and oxidative stress toxicity, the association is clinically relevant for different practitioners.