ARTICLE
Auteur(s) : Philippe
Humbert1, Fabien Pelletier1, Brigitte
Dreno2, Eve Puzenat1, François
Aubin1
1Department of Dermatology, University of
Franche-Comté, CHU Saint Jacques, 25030 Besançon, France
2Department of Dermatology, Hôtel Dieu, 1 place Alexis
Ricordeau, 44093 Nantes Cedex 1, France
accepté le 15 Juillet 2005
Gluten sensitivity with or without classical coeliac disease (CD)
symptoms and intestinal pathology has been suggested as a
potentially treatable cause of various diseases. CD is a chronic
disease, characterized by small bowel villous atrophy which impairs
nutrient absorption and improves on withdrawal of wheat gliadins
and barley, rye and oat prolamins from the diet [1]. The
alcohol-soluble prolamin fraction of gluten (gliadin in wheat,
secalin in rye, avenin in oats, and hordein in barley) is one of
the offending substances. CD has a wide variety of clinical
manifestations, including failure to thrive, chronic diarrhea,
abdominal pain and distension, muscle wasting, irritability. An
increasing number of patients should be diagnosed with subclinical
forms characterized by minor, transient or apparently unrelated
dermatological symptoms [1]. Maki et al. [2] estimate that the
prevalence of coeliac disease among Finnish schoolchildren is at
least one case in 99 children.Over the last few years there have
been numerous reports linking CD with several skin conditions.
Thus, gluten intolerance (GI) or CD gives rise to a variety of
dermatological manifestations which may benefit from the
gluten-free diet (GFD) given for GI or CD (table 1).To establish
the diagnosis of CD, an intestinal biopsy is usually needed. Indeed
anti-gliadine antibodies are not considered as a good marker for
CD. Thus anti-endomysial and anti-transglutaminase antibodies are
more specific and more sensitive markers for CD.Many diseases are
found with a higher frequency in patients with CD, but also in
dermatitis herpetiformis (DH). Some autoimmune diseases linked with
HLA DQ2 or DQ8 phenotype (e.g., diabetes mellitus, thyroid
disease), are particularly associated with CD. Moreover HLA typing
is often useful in association with serologic tests to diagnose
CD.Due to the high prevalence of gluten intolerance in the
population, it is thus probable that combination of CD with other
frequent diseases may be fortuitous. The strength of evident
association between gluten intolerance and the main skin diseases
is related in table 1.
Gluten intolerance and autoimmunity
Dermatitis herpetiformis
( Table 1 )Since the first observation
by Marks et al. [3] the relation between CD and dermatitis
herpetiformis (DH) has been well established. Nowadays a body of
evidence shows that DH is actually a cutaneous manifestation of CD
and may affect approximately twenty-five per cent of patients with
CD [4]. Twenty percent of patients with DH have clinical symptoms
of CD. However, in 80% of cases of DH, intestinal investigation
shows endoscopic and histologic changes consistent with CD [5].
From a statistical point of view, the main conditions associated
with DH are autoimmune thyroid disease, diabetes mellitus, lupus
erythematosus, Sjögren’s syndrome, sarcoidosis, vasculitis,
rheumatoid arthritis, vitiligo and alopecia areata [6, 7].
Considered as an autoimmune condition, DH can be associated with
more than one other autoimmune condition, leading to the concept of
Multiple Autoimmune Syndromes [8]. Nevertheless, in these cases,
the role of GI seems to be negligible. There is an increased
incidence of lymphoma in patients with DH as there is in patients
with CD. It has been shown that a gluten-free diet protects against
the development of lymphoma both in CD and DH [9]. Besides, DH is
associated in most cases with particular HLA phenotypes, i.e. A1,
B8 and/or DR3 [6]. These haplotypes confer a genetic predisposition
for autoimmunity. Two recent studies have raised the predominant
presence of the alleles DQB2 and DQ8 in both CD and DH [10, 11]. It
has now been claimed that transglutaminase (TGT) is the autoantigen
in CD and antibodies to TGT are present in the circulation. The
mechanism of how it induces the enteropathy has still to be
elucidated. In addition transglutaminase antibodies play a role in
the production of the skin lesions of patients with DH [6].
Furthermore a long term recent follow-up study of CD and DH showed
that first-degree relatives are frequently affected in CD and DH
[12].
Table 1 Strength of evidence for association between
gluten intolerance and main skin diseases
|
Proved association
|
Improvement in skin disease by gluten free-diet or/and presence
of serologic markers in several data
|
Fortuitous association (Sporadic cases reports)
|
|
Autoimmune diseases
|
Dermatitis herpetiformis
|
Alopecia areata
|
IgA linear dermatosis
|
|
Dermatomyositis
|
Vitiligo
|
|
Cutaneous vasculitis
|
Lupus erythematosus
|
|
Lichen sclerosous
|
|
Allergic diseases
|
|
Urticaria
|
|
|
Atopic dermatitis
|
|
Prurigo nodular
|
|
Inflammatory diseases
|
|
Psoriasis
|
Palmoplantar pustulosis
|
|
Pityriasis rubra pilaris
|
|
Erythroderma
|
|
Miscellaneous diseases
|
|
Oral mucosa
|
Necrolytic migratory erythema
|
|
Chronic ulcerative stomatitis
|
Cutaneous amyloidosis
|
|
Annular erythema
|
|
Partial lipodystrophy
|
|
Generalized acquired cutis laxa
|
|
Ichthyosis
|
|
Transverse leukonychia
|
IgA linear dermatosis
Linear IgA dermatosis is a rare bullous disorder first described by
Jablonska and Chorzelski in 1979 [13]. Linear IgA dermatosis is
often associated with malignancy, in particular lymphoma. And the
occurrence of lymphoma as a complication of CD is well recognized.
Nevertheless, the association of IgA linear dermatosis in a patient
with lymphoma and subsequent CD should probably be linked more to
the malignant condition [14].
A recent case report demonstrated that linear bullous dermatosis
can respond to gluten restriction if an underlying gluten-sensitive
enteropathy is present [15].
Benign chronic bullous dematosis of childhood is a distinct
clinical entity among the bullous diseases of childhood. It shares
with IgA linear dermatosis some immunopathological features. In an
eleven-year old patient, the bullous condition was associated with
CD [16] and responded well to GFD.
Bullous pemphigoid
Some authors showed antigliadin antibodies in the serum of patients
with bullous pemphigoid [17] and in chronic benign mucous membrane
pemphigoid [18] as well, suggesting similar particularities with
DH. If there is no evidence that these patients have
gluten-sensitive enteropathy, either clinically or histologically,
it is assumed that their mucosa may be permeable to proteins such
as gliadin.
Alopecia areata
Patients with alopecia areata were recently found to be at high
risk of gluten-sensitive enteropathy [17]. The prevalence of
gluten-induced enteropathy in patients with alopecia is from 1:89
[19] to 1:116 [20], and is significantly higher than that of CD in
the general population (1:305) [21]. Thus, only two out of 232
patients with alopecia areata were positive for IgA antibodies, and
had a severe partial or subtotal villous atrophy [20].
Nevertheless, in only one of the two cases of this study was the
withdrawal of gluten from the diet followed by a partial regrowth
of scalp, which was affected by alopecia universalis. Benefits from
a GFD also occurred in some other cases [19, 20, 22]. However, in
one case, alopecia areata developed after the beginning of such a
diet [23], and in five alopecic patients with CD, both conditions
seemed to have an independent course, GFD being successful for the
CD but not for alopecia areata [24]. In two other reports of three
cases [25], low serum zinc levels were detected, but zinc
supplementation did not improve the scalp condition, whereas GFD
led to regrowth of hair respectively within the year in two cases,
and after 2 years in the other one.
Recently Storm described a young girl with Down’s syndrome,
alopecia areata and documented CD, who displayed a normal growth of
hair after a gluten-free regimen [26].
Thus, it is noteworthy that gluten sensitive enteropathy needs
to be searched for in alopecia areata, even if the frequency of the
association is rare. Indeed, GFD could be beneficial in some
patients.
Vitiligo
The possible relation between vitiligo and GI remains a debated
question [27]. In a study, none of the 198 patients with vitiligo
who were screened for IgA antibodies, was positive [20], and the
authors concluded that the sporadic associated cases must be
considered coincidental.
Lupus erythematosus
A few previous reports of protein-losing enteropathy leading to
malabsorption have been described associated with systemic lupus
erythematosus (SLE) [28]. In a series of twenty-one SLE patients,
the prevalence of malabsorption was approximately ten per cent but
the pathogenesis is not yet clear and needs further investigation
[29]. Also, gluten enteropathy has been described in a case of
sub-acute cutaneous lupus erythematosus [30]. Twelve months after a
successful GFD on gastro-intestinal symptoms, the patient developed
erythematous annular and gyrate lesions on the face, neck and
forearms. The relation between both conditions might be due to the
presence of HLA DR3 which has a high incidence in subcutaneous
lupus erythematosus and in gluten sensitive enteropathy. However,
GFD was unsuccessful in preventing lupus erythematosus. Moreover, a
recent American study examined the prevalence of CD autoantibodies
in SLE patients [31]. Twenty-four of one hundred and three patients
tested positive for antigliadin antibody, whereas none of the
twenty-four antigliadin positive patients was found to have
endoscopic or histological evidence of CD. Antiendomysial
antibodies were also negative in these patients. In fact, false
positive antigliadin antibodies with SLE are common. There does not
seem to be an association between CD and SLE, although previous
cases in the medical literature have described the diagnosis of CD
in patients with known SLE and the diagnosis of SLE in patients
with CD [32-35].
Scleroderma
Systemic sclerosis may be associated with other different
autoimmune diseases [36].
Among these conditions, CD may be one of the different causes of
malabsorption in scleroderma patients [37].
Polymyositis and dermatomyositis
A wide range of neuromuscular diseases may be the presenting
feature of CD [38]. Polymyositis may be associated with CD in some
patients [39-42]. In some cases, treatment with GFD resolved
clinical and laboratory abnormalities [41, 42].
Juvenile dermatomyositis, as well as dermatomyositis in adult
patients, may exhibit malabsorption syndrome. Especially when
patients present with unusual and unexplained gastrointestinal
features, an evaluation for CD should be considered, and could lead
to its early management [43-46].
Sclero-atrophic lichen
Probably due to its low frequency, only one report of
sclero-atrophic lichen has been described associated with CD [47].
Cutaneous vasculitis
When associated with cryoglobulinemia, it is not surprising to
observe cutaneous vasculitis in the course of CD [48]. In other
cases [49-51], cutaneous vasculitis occurred in the presence of
severe, poorly controlled bowel disease. The increased intestinal
permeability of CD [52] (intestinal hyper-permeability does not
mean increased absorption, both mechanisms being different) could
induce the production of immune complexes which are the
pathophysiological factors involved in leucocytoclastic vasculitis.
Thus, these patients are likely to improve on a GFD [51].
Erythema elevatum diutinum
Erythema elevatum diutinum should be regarded as a rare variant of
cutaneous leucocytoclastic vasculitis. Dapsone is known to be
effective in some cases. A few cases have been described in
association with CD [53, 54]. In these cases GFD was successful in
improving cutaneous symptoms. The erythema elevatum diutinum skin
lesions could be the result of immune complex deposition composed
of IgA, which could merely constitute a marker of the disease.
Gluten intolerance and allergic diseases
Urticaria
Different immuno-allergical manifestations, such as asthma, eczema,
hayfever and urticaria could be improved by a GFD, when they are
associated with CD [55, 56]. Moreover, histological alterations of
the small bowel mucosa consistent with the diagnosis of CD were
found in some patients with urticaria [57]. These experiences
suggest that CD should at least be considered when studying
patients with chronic urticaria, even in the case of hereditary
angioneurotic, which can be associated with CD [58].
Atopic dermatitis
Cereal allergy or intolerance can be one of the underlying causes
of atopic dermatitis in some patients. Despite the role of cereal
products in the beginning or the course of the disease in some
patients with atopic dermatitis, the coexistence of CD seems to be
rare [59], with a prevalence of 1%, which is nevertheless higher
than that in the general population [60]. Atopic dermatitis can be
one of the underlying symptoms of the so-called subclinical CD (the
characteristic symptoms of CD being absent), especially in children
[61]. Since food allergy seems to play an important role in atopic
dermatitis, occult enteropathy should thus be suspected in patients
with atopic dermatitis [57]. Skin prick tests and
radioallergosorbent tests allow the detection of wheat-allergic
atopic dermatitis patients, suggesting in such cases an
IgE-dependent allergic mechanism [62]. On the contrary, the
presence of IgA and IgG antibodies to different cereal antigens
displays little diagnostic significance in atopic dermatitis [63].
Prurigo nodularis
Prurigo nodularis is sometimes considered as an itching condition
related to psychological disorders, or due to different mechanisms
[64]. Since the description by Wells in 1962 of six patients with
eczematous skin manifestation associated with steatorrhea [65], one
of them having been cleared after a GFD [66], the underlying role
of GI was suggested again. Howell [67] described a female aged 53
years who was shown to have gluten enteropathy associated with a
so-called exsudative nummular prurigo. Appropriate treatment of her
gut and skin led to substantial improvement. McKenzie et al. [66]
reported two female patients with suspected GI in whom a GFD did
not clear nodularis prurigo, but increased the sense of well-being.
The underlying intestinal disturbance in patients with prurigo
nodularis seems to be unquestionable when considering some
published cases with malabsorption. Gluten might be one of the
related factors responsible for malabsorption. Two other cases give
clues to this pathological link between both skin and gut
conditions [68, 69] since both patients significantly improved
under GFD. In one case, prurigo nodularis preceded by 15 years the
onset of CD, and both conditions showed a similar and concomitant
course [70]. The combination of CD, DH and prurigo nodular has just
been reported in a 40-year-old woman [71]. The response to gluten
withdrawal of both skin diseases suggests the possibility that
prurigo nodular also should alert to CD.
Gluten intolerance and deficiencies
The following skin conditions may be due to deficiency symptoms
related to malabsorption. Hemorrhagic diathesis [72], iron
deficiency, and scurvy have a clinical dermatological expression,
and should be explored to detect subclinical CD.
Scurvy is usually due to alcoholism, a limited diet and poor
socio-economic conditions. It has been described related to Whipple
disease [73], Crohn’s disease [74] and CD [75]. When not diagnosed,
CD induces long term malabsorption of different nutriments. Among
them, ascorbic acid deficiency occurs very early on. Indeed, only a
three-month deficiency period is necessary to completely deplete
the vitamin C stocks of the body.
Gluten intolerance and psoriasis and related conditions
Psoriasis
In 1971, Shuster and Marks described a psoriatic enteropathy in a
small group of patients with severe psoriasis and gastro-intestinal
changes similar to CD [76], In 1976, Bazex et al. [77] examined 16
patients with severe psoriasis. In 11 patients, they showed a clear
atrophy of the intestinal mucosa. All four patients with psoriatic
rheumatism presented with malabsorption. It was not possible to
precisely evaluate the benefit of GFD in this series, nevertheless
the conviction of the authors was that patients got better and that
psoriasis improved. In one case, they observed the relapse of
psoriasis three days after the withdrawal of the GFD. For many
years, Michaëlsson et al. have been taking into consideration the
role of gluten in the determinism of psoriasis [78-84]. Their first
reports involved six patients with moderate to severe psoriasis,
and one with severe palmo-plantar pustulosis, with durations of
6-37 years, and total or almost total clearance of the lesions on a
GFD with no other treatment [78]. Their conclusion was that the
response to a GFD was impressive. These results prompted them to
question whether GI might be more common in patients with psoriasis
than in healthy subjects [79]. Three hundred and two patients were
compared with blood donors. Sixteen per cent of the patients had
IgA antigliadin antibodies values above the 90th
percentile of the reference subjects. There was a more pronounced
tendency in male than in female patients, and in the male group a
trend to a correlation between IgA antigliadin antibodies and the
age of the patient was demonstrated. The authors noticed that
raised serum levels of antibodies to gliadin were more common in
patients with psoriasis requiring systemic therapy.
The question remains as to whether the enteropathy is secondary
or not to the skin disease. Different data, including increased
intestinal permeability [85] suggest an intestinal involvement in
psoriatic patients. Moreover, 42% of psoriasis patients with
moderately elevated levels of serum IgA and/or IgG antibodies to
gliadin had an increased number of mononuclear cells in the
duodenal epithelium [80]. Independently of the presence of IgA
antigliadin antibodies, psoriasis patients may have a pronounced
increase of EG2+ eosinophils and tryptase + mast cells in their
duodenal stroma [81, 82].
Furthermore, the effect of a GFD in the 33 previously reported
patients was evaluated [84]. After a 3-month GFD period followed by
all these patients, thirty of them, who were suspected to have GI,
showed a highly significant decrease in mean PASI (psoriasis area
and severity index). In addition, six of the antigliadin
antibody-negative patients did not improve. The positive effects
were observed not only in patients with an increased number of
lymphocytes in the duodenal epithelium but also in some patients
with seemingly normal epithelium.
All these findings raise questions about how they could be
explained [86]. Nevertheless, Reunala et al. did not observe any
increased incidence of psoriasis among patients with CD or DH [7].
It has been suggested that determining the levels of tissue
transglutaminase antibodies in psoriasis patients improves the
sensitivity and the specificity of the research of gluten sensitive
enteropathy [87, 88]. However, the absence of randomized studies
concerning the beneficial effect of a GFD in psoriasis still
suggests a placebo effect of this therapy.
In addition, due probably to its frequency, CD has been
associated with psoriatic arthritis [88]. Lindqvist et al. [89]
showed that patients with psoriatic arthritis had an increased
prevalence of raised serum IgA antibodies to gliadin and of coeliac
disease (4.4%). Patients with raised IgA antibodies to gliadin
seemed to have more pronounced inflammation than those with low IgA
antibodies to gliadin concentration.
Palmoplantar pustulosis
Among the conditions known to be associated with palmoplantar
pustulosis, Eriksson et al. [83] noticed a high prevalence of
antigliadin antibodies in ten of 39 patients examined. Two of them
were known to have gluten hypersensitivity.
Pityriasis rubra pilaris
Pityriasis rubra pilaris (PRP) is a disease of unknown etiology.
The association of PRP with CD in one case [90] may bring a clue to
its cause. If malabsorption may be present in some patients with
PRP, causing decreased concentrations of serum carotene and vitamin
A, the origin of the enteropathy remains unknown. In the present
case, the enteropathy preceded the PRP by more than thirty years.
The authors came to the conclusion of a coincidental finding, even
if hyperkeratosis became minimal after vitamin A therapy followed
by a GFD.
Erythroderma
Pruritic eczema of a seborrheic or psoriasiform pattern has been
reported as a cutaneous manifestation of CD. A minority of adults
can be affected, but also children, where the condition can be of
particular severity [91].
Gluten intolerance and miscellaneous
Necrolytic migratory erythema
Necrolytic migratory erythema (NME) is a characteristic skin
disease mainly associated with glucagonoma. The skin eruption may
occur during the course of other conditions, some of them being
characterized by intestinal dysfunction. Deficiencies in zinc,
amino acids or essential fatty acids have been taken into
consideration. Three cases of NME have been described in patients
with gluten sensitive enteropathy [92, 93] in which symptoms
completely resolved with adherence to a GFD. In one case NME was
associated with an excess production of enteroglucagon by the
intestinal mucosa, which could be due to exposure of the distal gut
to unabsorbed nutrients because of the associated CD [92].
Annular erythema
Annular erythema might also be considered as a clinical
manifestation of DH or from a more general point of view, as the
expression of GI. The successful GFD in a 5-year old girl with
annular erythema and cutaneous histopathological aspects of DH [94]
shows that annular erythema is a plurifactorial condition and that
the role of GI must be evoked in some cases.
Malignancies
Patients with CD have a higher risk than the general population for
the development of malignancies and particularly lymphomas [95-99].
Lymphomas usually involve gut and lymph nodes, but can also have
skin locations, as it was presumed in a case of primary T cell
CD30-positive anaplastic large-cell lymphoma [100]. A Swedish study
followed up 12,000 patients with CD or DH and evaluated cancer
incidence [101]. Adults (but not children or adolescents) with CD
had an elevated overall risk of cancer that declined with time.
Elevated risks were found for malignant lymphoma, small-intestinal,
oro-pharyngeal, esophageal, large intestinal, hepatobiliary and
pancreatic carcinomas.
Pseudopurpuric palmar lesions
Pseudopurpuric palmar involvement could be now considered as an
unusual clinical manifestation of DH [102], and has been reported
associated with IgA linear dermatosis [103]. In the reported cases,
the palmar lesions looked like purpuric angiokeratomas, their
intermittence allowing to distinguish them from this condition.
These lesions respond partially to a GFD or sulfone treatment.
Partial lipodystrophy
In a patient with serum IgA and C3 complement deficiencies and CD,
partial lipodystrophy was described [104]. Partial lipodystrophy is
characterized by a noticeable global reduction of adipose tissue
above the waist and a normal or hypertrophic appearance of the
buttocks and lower limbs. This condition is coupled with C3
hypocomplementemia due to accelerated C3 complement factor
degradation because of the presence of a serum complex, the
so-called C3 nephritic factor, stabilizing the C3 convertase
enzyme. Partial lipodystrophy has been reported in combination with
different autoimmune conditions. The underlying immunological
abnormalities in the course of this condition could induce the
development of autoimmunity.
Generalized acquired cutis laxa
A possible immunological abnormality has been postulated by some
authors to explain the destruction of elastic tissue in the course
of acquired cutis laxa (ACL). Glutenin which is one of the main
components of gluten, presents a secondary structure and several
amino acid sequences similar to elastin [105]. The association of
progressive ACL and patterns of CD in a patient [106] and the
moderate improvement of the papular eruption with dapsone and GFD
support the hypothesis of a link between GI and the condition. The
possible role of some antibiotics, especially penicillin, is of a
particular interest in patients with gluten sensitive enteropathy
who developed generalized ACL [107].
Cutaneous amyloidosis
Lichen amyloidosis is one of the clinical patterns of primary
cutaneous amyloidosis. It may succeed to an itching condition such
as chronic eczema, the deposition of amyloid being considered as
secondary to lichenification. Thus, since eczema may be a cutaneous
manifestation of gluten sensitive enteropathy, the report of a case
where lichen amyloidosis followed chronic eczema associated with CD
is not surprising [108]. Amyloid deposits were not responding to a
GFD whereas eczema significantly improved.
Oral mucosa
Apart from the intestine and the skin, coeliac sprue can also
involve oral mucosa. Recurrent oral ulceration is the most frequent
presenting symptom. Mouth ulcers are one of the most common
complaints of the population. Recurrent oral aphthae may be the
unique manifestation of GI, and may lead to the diagnosis of CD
[109]. About 4% of patients with recurrent aphthae are supposed to
have CD [110]. In such cases aphthae can result from iron, folate
or vitamin B12 deficiency induced by CD. The oral cavity of
patients suspected of having CD needs to be examined, since no less
than 66% of the patients have oral mucosal lesions or dental enamel
defects [111].
Even if CD has been excluded in some patients with recurrent
aphthous stomatitis, a GFD shows a beneficial therapeutic effect in
25% of them [112]. Furthermore, the association with oral mucosal
lichen planus should be considered, since one patient suffered from
both conditions in a series of 39 patients with oral mucosal lichen
planus. Moreover, about one third of these patients had IgA
anti-gliadin autoantibodies [113].
In 1990, Jaremko et al. [114] identified a new disease involving
the oral mucosa which was named chronic ulcerative stomatitis.
Unusual anti-nuclear antibodies (stratified epithelium-specific
antibodies) SES-ANA have been described in the course of chronic
ulcerative stomatitis.
Chorzelski et al. [115] have published a cohort which comprised
15 cases of chronic ulcerative stomatitis with typical clinical
features and immunological findings. Among these cases, one woman
had high titers of IgA EmA detected in the serum, and a duodenal
biopsy disclosed flat mucosa and inflammatory infiltrates in the
lamina propria. The diagnosis of latent coeliac disease was
confirmed. A gluten free diet was able to clear the mucosal and
skin lesions, with occasional slight cutaneous relapses.
The relationship between chronic ulcerative diseases and CD is
not known, however both cutaneous and mucosal lesions responded to
the gluten free diet.
Ichthyosis
Menni et al. [116] described a patient with coeliac disease
revealed by the sudden appearance of a keratinization disorder. The
woman presented with lamellar scaling lasting for some months.
Anti-endomysial antibodies were positive, and a duodenal biopsy
showed total atrophy of the villi. A gluten-free diet corrected the
biological markers of malabsorption. Six months later, milder
lamellar scaling was still detectable and serum values were normal
except for sideraemia.
Acquired ichthyosis with bowel disorders such as Crohn’s disease
and coeliac disease has also been already reported [117].
Nails
Transverse leukonychia in severe hypocalcemia caused by
hypoparathyroidism and coeliac disease has been reported [118].
Transverse leukonychia disappeared after calcium supplementation.
Persistant lower calcium levels were probably due to the
concomitant presence of coeliac disease.
Conclusion
GI or CD should be kept in mind when investigating certain
cutaneous conditions, and especially diseases with immunological or
allergic pathophysiological mechanisms [119]. Dermatologists should
be familiar with the appraisal of gluten sensitive enteropathy, and
should be able to search for an underlying GI. GI or CD is a
frequent disorder: coincidental observations can be observed with
other common diseases. Moreover, high titers of anti-gliadine
antibodies are not synonymous with GI. To establish whether some
cutaneous conditions, especially immunologically mediated skin
diseases, could be related to gluten-sensitive enteropathy, a
serological screening by means of antigliadin, antiendomysial and
transglutaminase antibodies, which are considered to be the most
reliable serological markers of CD [120, 121] in large series of
consecutive patients with these conditions should be performed. HLA
typing can be a good tool to reveal links between skin diseases and
GI. The diagnosis is confirmed by intestinal biopsy. Such an
analysis could lead to establish the prevalence of CD among these
patients.
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