1. A previously healthy 8-year-old girl presents with a 3-month history of
persistent, intensely pruritic papules distributed symmetrically on her hands,
thighs, elbows, and buttocks (Figure 1). Thorough questioning may also
reveal:
A. Negative review of systems
B. No relief from oral diphenhydramine
C. Positive family history of celiac disease
D. All of the above
2. This 5-year-old boy presents with similar findings for 6 months duration
(Figure 2). Skin biopsy to aid in the diagnosis of this condition should be
performed:
A. For histopathology and direct immunofluorescence of the freshest
lesion
B. For histopathology and direct immunofluorescence of the most
established lesion
C. For histopathology and tissue culture
D. For histopathology, tissue culture and viral cultures
3. The diagnosis of dermatitis herpetiformis has been made in this
9-year-old boy (Figure 3). The most appropriate therapy includes:
A. Oral corticosteroids
B. Oral antihistamines and topical corticosteroids
C. Gluten-free diet and oral dapsone
D. Oral valacyclovir
Answers: 1D, 2A, 3C
Discussion:
Dermatitis herpetiformis (DH) is considered a
dermatologic hallmark of celiac disease (immune-mediated gluten sensitivity) in
both children and adults, as 100% of affected patients demonstrate subclinical
or latent gastrointestinal disease.[1] It typically presents as a persistent,
intensely pruritic, papulovesicular eruption, and has a pathognomic appearance
on skin biopsy with direct immunofluorescence. It is the most common
immunobullous skin condition seen in adolescents, though it is quite rare in
prepubertal children.[2] When DH does occur in younger children, it is most common in those aged 2 to
7 years, though
it has been reported in an infant as young as 8 months
of age.[1] Importantly for the pediatric clinician, cutaneous
findings may occur in the absence of, or frequently precede,
gastrointestinal symptoms. And while DH itself is rare, celiac disease is
not: estimated prevalence in the United States is approximately 1:80 to 1:300
children,[3] and may be increasing due to more heightened awareness of this
diagnosis. Both DH and celiac disease are strongly associated with HLA (human leukocyte antigen) serotypes DR3 and DQw2,[4]
and approximately 10% of patients with DH will have 1 or more first-degree
relatives with gluten sensitivity.[5] Thus increased suspicion for this condition is
warranted in a child with a positive family history.
Clinically, DH typically presents as extremely itchy, 1-3 mm erythematous
papules and edematous plaques with superimposed vesicles, with striking
predilection for the elbows, knees and buttocks in a symmetric distribution.
Lesions are characteristically grouped, hence the "herpetiform" description, as
they can resemble outbreaks of herpes virus. The nape of the neck and scalp may
also be involved, as can any area of the skin. Mucosal involvement is rare, but
if present, is usually asymptomatic. Patients may describe a prodrome of
stinging or burning in the affected skin prior to the eruption of visible
lesions. Due to the intense pruritus, clinicians most often see unroofed or
crusted lesions, as the primary lesion has been excoriated. Antihistamines and
other anti-pruritic measures usually offer little relief.
In children, several unusual clinical variants have been described,
including a case mimicking chronic urticaria,[6] chronic deep nonpruritic dermal
papules or nodules,[7] palmoplantar erythematous plaques,[8] and isolated palmar
purpura.[9] In all such cases, skin biopsy was diagnostic.
Differential diagnosis of DH in children includes: papular
dermatitis/eczema, urticaria/papular urticaria, scabies, arthropod bites,
chronic bullous disease of childhood (linear IgA dermatosis), pityriasis
lichenoides et varioliformis acuta, erythema multiforme, lupus erythematosus,
bullous pemphigoid, factitial dermatitis and vasculitis. The absence of typical
atopic background, as well as the presence of vesicles on exam, should help to
distinguish this entity from papular atopic dermatitis.
Diagnosis of DH is based on clinical findings, and confirmed with
histologic and laboratory evaluation. Ideally, skin biopsy of the newest
affected area should be performed, and immunofluorescent analysis of
perilesional skin should always be included. Histopathology reveals classic
features of subepidermal blistering, with groups of neutrophils and eosinophils
at the dermal-epidermal junction. Direct immunofluorescence demonstrates
pathognomic granular deposits of IgA at the tips of dermal papillae.
Once the diagnosis of DH is confirmed, an evaluation for the presence of
celiac disease should be performed. Gastrointestinal symptoms may be minimal or
absent at the time of presentation. Suggested testing includes measurement of
IgA antibody to human recombinant tissue transglutaminase (TTG), recently
confirmed as the most reliable diagnostic test for gluten sensitivity.[10] In
addition, baseline IgA levels should be measured, as those patients deficient in
IgA will not have abnormally elevated levels of TTG IgA as otherwise
expected.
Treatment of DH usually involves the combination of sulfone medication
and dietary modification. Dapsone (initial dosage of 2 mg/kg/day) can provide
dramatic relief of pruritic symptoms, typically within 24 to 48 hours after
beginning therapy.[11] Baseline complete blood count and glucose-6-phosphate
dehydrogenase (G6PD) level should be checked prior to initiating this
medication, weekly blood counts repeated for the first month, and monthly checks
continued for the next 5 months. Patients should be also counseled on potential
side effects including hemolytic anemia, methemoglobinemia, leukopenia,
gastrointestinal symptoms, peripheral neuropathy, headache, exfoliative rash,
liver toxicity and lymphadenitis. Fortunately, these side effects are rare. Once
suppression of symptoms has been achieved, dosage can be tapered as tolerated.
If dapsone cannot be used or is ineffective, sulfapyridine may be an acceptable
alternative.
In addition to pharmaceutical therapy, a strict gluten-free diet should
also be strongly encouraged. In fact, many patients can achieve total resolution
of skin disease by diet alone,[12] though dapsone may be necessary to control
symptoms until dietary changes take full effect. Maintaining a gluten-free diet
also leads to regression of small intestinal lesions, if present. DH and celiac
disease have been associated with an increased risk of developing small bowel
lymphoma, and adherence to a gluten-free diet may be protective against the
development of this malignancy in affected patients.[13] Sustaining this diet
can be difficult for anyone but the most highly motivated patient, however, and
referral to a nutritionist or support group (such as the Gluten Intolerance
Group, www.gluten.net, or the National Foundation for Celiac Awareness,
www.celiaccentral.org) may be helpful.
References
[1.] Lemberg D, Day AS, Bohane T. Coeliac disease presenting as
dermatitis herpetiformis in infancy. J Pediatr Child Health
2005;41:294-296.
[2.] Weston W, Morelli J, Huff J. Misdiagnosis, treatment, and outcomes
in immunobullous diseases in children. PediatrDermatol
1997;14:264-272.
[3.] Hill ID, et al. North American Society for Pediatric
Gastroenterology, Hepatology and Nutrition. Guideline for the diagnosis and
treatment of celiac disease in children: Recommendations of the North American
Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr
2005;40:1-19.
[4.] Karell K, et al. Genetic dissection between celiac disease and
dermatitis herpetiformis in sib pairs. Ann Human Genet 2002;66:387-392.
[5.] Reunala T. Incidence of familial dermatitis herpetiformis. Br J
Dermatol 1996;134:394-398.
[6.] Powell GR, Bruckner AL, Weston WL. Dermatitis herpetiformis
presenting as chronic urticaria. Pediatr Dermatol 2004;21:564-567.
[7.] Woolans A, et al. Childhood dermatitis herpetiformis: An unusual
presentation. Clin Exp Dermatol 1999;24:283-285.
[8.] Karpati S, Torok E, Kosnai I. Discrete palmar and plantar symptoms
in children with dermatitis herpetiformis Duhring. Cutis
1986;37:184-187.
[9.] McGovern T, Bennions S. Palmar purpura: An atypical presentation of
childhood dermatitis herpetiformis. Pediatr Dermatol 1994;11:319-322.
[10.] Caproni M. Tissue transglutaminase antibody assessment in
dermatitis herpetiformis. Br J Dermatol 2001;144:196-197.
[11.] Paller AS, Mancini AJ. Dermatitis herpetiformis. In Hurwitz
Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and
Adolescence, 3rd ed. Philadelphia, PA: Elsevier Saunders; 2006:359.
[12.] Garioch JJ, et al. Twenty-five years' experience of a gluten-free
diet in the treatment of dermatitis herpetiformis. Br J Dermatol
1994;131:541-545.
[13.] Collin P, Pukkala E, Reunala T. Malignancy and survival in
dermatitis herpetiformis: A comparison with coeliac disease. Gut
1996;38:582-530.
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