Dermatitis herpetiformis Duhring: Dermatitis herpetiformis Duhring (DhD) is an epiphenomenon of gluten-sensitive enteropathy (CD) - see below. Dermatitis herpetiformis.
Dermatomyositis: The association of dermatomyositis and celiac disease (CD) has been reported several times, a genetic predisposition seems to play an important role (Soo Song M et al. 2006; Marie I et al. 2001; Iannone F et al. 2001). In patients with concomitant CD and dermatomyositis, a gluten-free diet can improve DM (Muddasani S 2021).
Systemic lupus erythematosus: CD individuals have a threefold increased risk of systemic lupus erythematosus compared to the general population (Ludvigsson JF et al. 2021). A recent study found a prevalence of 3% for biopsy-proven CD in SLE patients (Soltani Z et al. 2021). In an adolescent SLE population, CD was even detected in 6% of patients (Hamseya AM et al. 2020).
Chilblain lupus: Another autoimmunological skin disease associated with CD is chilblain lupus. The links are still unclear (Mašić M et al. 2022; Lemieux A et al. 2020).
Sjögren's syndrome: The association between Sjögren's syndrome (SS) and CD has been described in several case reports (Balaban DV et al. 2020). The prevalence of CD in patients with SS is between 1.2 % and 6.5 % (Ayar K et al. 2020)
Systemic scleroderma: The coexistence of CD and systemic sclerosis (SSc) has been reported in some publications. Prevalences ranged from 4% to 8% (Nisihara R et al. 2011), although the link between these two conditions remains controversial.
Alopecia areata: Overlapping symptoms include alopecia areata (AA). The risk of developing alopecia areata is three times higher in patients with CD than in the general population (Bondavalli P et al. 1998; Xing L et al. 2014). Improvements in AA after starting a gluten-free diet (GFD) in CD patients have been observed (Corazza GR et al. 1995).
Vitiligo: The relationship between CD and vitiligo is still controversial. Some authors found a higher incidence of vitiligo in CD patients, others could not confirm this correlation (Verdelli et al. 2023)
Psoriasis: The risk of developing psoriasis is increased by a factor of 1.7 (1.54-1.92) in people with coeliac disease. A recent meta-analysis found the overlap of 10 psoriasis susceptibility loci with those of CD, including a single nucleotide polymorphism (rs6822844) that is strongly associated with CD and with both psoriasis and psoriatic arthritis (Collaborative Association Study of Psoriasis (CASP) 2012). Given the altered intestinal barrier in CD, it can be assumed that increased permeability to immunogenic triggers may lead to a higher prevalence of immune-mediated diseases (Verdelli A et al. 2023). In addition, a meta-analysis (Bhatia BK et al. 2014) showed a higher rate of positive anti-gliadin IgA antibodies in patients with psoriasis compared to control subjects, suggesting a possible role of gluten in the aetiogenesis of these patients. Other studies indicate a correlation between the level of CD antibodies and the severity of psoriasis or psoriatic arthritis (Woo, WK et al. 2004)
Atopic dermatitis: In a large study by Shalom et al. (Shalom G et al. 2020) of 116,816 patients (including 45,157 adults), atopic dermatitis was associated with a significantly higher prevalence of CD. The prevalence of AD was significantly higher in a pediatric celiac population compared to ulcerative colitis or Crohn's disease. Children with atopic dermatitis were found to be four times more likely to develop CD. Of note is a case-control study of 4,114 adult patients in which the incidence of Alzheimer's disease is threefold higher in CD patients and twofold higher in their relatives than in their spouses.
RAS (recurrent apthous stomatitis): In a meta-analysis (Nieri M et al. 2017), the authors demonstrated a higher incidence of recurrent aphthous stomatitis (RAS) in CD patients (OR: 3.79, 95%CI: 2.67-5.3). This association was mainly studied in pediatric populations. It is not known whether RAS lesions are directly influenced by gluten sensitivity disorder or whether they are related to low serum levels of iron, folic acid and vitamin B12 or deficiency of trace elements due to malabsorption in patients with untreated CD. Local and systemic conditions, immunologic and microbial factors, and oral dysbiosis may also play a pathogenic role in these mucosal ulcers.
Chronic spontaneous urticaria: In one study, the odds ratio for the presence of CD in patients with CU was 26.9 (95% CI, 6.6-110.17; p < 0.0005) compared to controls. Therefore, CD screening should be suggested in CU (Kolkhir P et al. 2017)
Rosacea: A link between CD and rosacea has also been demonstrated. One study showed a higher risk of CD in women with rosacea. In a cohort study, the prevalence of CD was higher in patients with rosacea compared to controls (Egeberg A et al. 2017).
Cutaneous vasculitis: Several studies have found an association between CD and cutaneous vasculitis (CV). The literature suggests that CV is more likely to occur in patients with poorly controlled CD and that a GFD may improve CV lesions in such cases (Meyers S et al. 1981).
Acrodermatitis enteropatica as a consequence of CD: A typical feature of CD is malabsorption and subsequent deficiency of trace elements. Among these, zinc deficiency is the most common and causes diffuse alopecia and seborrhoidal scaling in the perioral regions and around the genitals and bends of the arms. In these patients, the skin symptoms improve with a GFD and oral zinc supplementation.
Neurological-psychiatric diseases (affecting a dermatologic consultation):
-
Migraine: a prevalence study describes a 3.8-fold increased risk of migraine for people with coeliac disease.
- Depression and anxiety disorders
- Epilepsy: A large epidemiological study (n= 29,000 celiac disease patients and 143,000 controls) describes an up to 1.7-fold increased risk for the manifestation of epilepsy.
Other
-
IgA deficiency: IgA deficiency is significantly more common in people with coeliac disease than in the normal population (approx. 2-3%).
- Irritable bowel syndrome (IBS): For those affected, the overall risk of coeliac disease is about 4 times higher. Screening IBS patients for coeliac disease makes sense. In people with microscopic colitis, concomitant coeliac disease is detected in approx. 5% of cases
-
Skin symptoms as a consequence of intestinal malabsorption: Secondary intestinal malabsorption can also cause muco-cutaneous manifestations due to nutrient deficiency. Zinc deficiency in CD patients has been associated with crusty-erythematous-scaly dermatitis localized in perioral regions, genitalia and skin folds. In addition, diffuse alopecia, stomatitis, balanitis, vulvitis and proctitis have also been found in these patients (Rodrigo L et al. 2018). Iron deficiency is associated with atrophy, xerosis, pruritus, hair loss, atrophic glossitis, angular stomatitis and koilonychia, while vitamin A deficiency can cause pytiriasis rubra pilaris-like lesions. Low serum levels of vitamin B12 and folic acid have been associated with angular stomatitis, glossitis, oral aphthosis and hyperpigmentation (Rodrigo L et al. (2018). Finally, pellagroid phenomena may also occur.
- Oral involvement: CD patients are affected by both dental and oral mucosal abnormalities, including enamel defects, RAS, delayed tooth eruption, multiple caries, angular cheilitis, atrophic glossitis, dry mouth and tongue burning. Furthermore, higher prevalences of enamel defects are observed.