Dermatitis herpetiformis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Dermatitis herpetiformis is a neutrophilic blistering eruption caused by IgA autoimmunity associated with gluten-sensitive enteropathy. It is classically symmetrical over extensor elbows and knees, buttocks, sacrum, shoulders and scalp. Vesicles are small, grouped and exquisitely itchy, but most patients present with excoriations, crust and post-inflammatory pigment rather than intact blisters. In richly pigmented skin, active inflammation may appear violaceous, grey or dark brown and residual hyperpigmentation can dominate the visible picture.

The intestinal disease may be clinically silent. Epidermal transglutaminase antibodies and granular IgA deposits in dermal papillae connect skin to the tissue-transglutaminase-driven coeliac response. Confirmation requires the right skin site and dietary state. Routine histology from a lesion can show a subepidermal neutrophilic blister but is less specific; direct immunofluorescence from nearby normal skin is decisive. Coeliac serology and gastroenterology assessment proceed while gluten remains in the diet.

Treatment has different clocks. Dapsone often stops itch within 48 to 72 hours but can cause dose-dependent haemolysis and methaemoglobinaemia plus rare agranulocytosis or hypersensitivity. Gluten exclusion takes longer to suppress cutaneous IgA but treats the enteropathy and permits dapsone reduction. A specialist dietitian is essential to protect nutrition, identify hidden gluten and make a lifelong diet practical rather than simply issuing a prohibited-food list.

Key points

Dermatitis herpetiformis is a very itchy symmetrical eruption of grouped papules and small vesicles on elbows, knees, buttocks, shoulders and scalp; scratching often removes intact blisters before examination.
The name describes a herpes-like grouping, not herpes infection. It is the skin manifestation of gluten-sensitive coeliac disease and can occur without gastrointestinal symptoms.
Take direct-immunofluorescence tissue from normal-appearing perilesional skin, not an excoriated lesion; granular IgA at dermal papillary tips is the diagnostic pattern.
Check total IgA with IgA tissue transglutaminase while the person is still eating gluten and use an IgG-based pathway when IgA deficient.
A strict lifelong gluten-free diet treats intestinal disease, nutritional and lymphoma risk and eventually reduces the skin's dapsone requirement, but improvement takes months to years.
Dapsone controls itch and new lesions within days but does not heal gluten-sensitive enteropathy; it is a bridge and adjunct, not a substitute for dietetic treatment.
Before dapsone, check G6PD, full blood count, reticulocytes, liver and renal function and establish frequent early blood monitoring.
Dapsone commonly lowers haemoglobin and raises methaemoglobin to some degree; clinically important cyanosis, dyspnoea, jaundice, fever or mouth ulcers requires urgent testing and cessation.
Do not advise gluten withdrawal before coeliac serology, histology or specialist diagnosis unless unavoidable, because reduced exposure lowers diagnostic sensitivity.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Gluten-sensitive autoimmunity

Dietary gluten drives a coeliac immune response in genetically susceptible people, with related IgA recognising epidermal transglutaminase in skin.

HLA-associated susceptibility

Most patients carry coeliac-associated HLA-DQ2 or DQ8, but these common alleles support susceptibility and cannot diagnose disease alone.

Persistent hidden exposure

Cross-contact, misunderstood labels and unrecognised gluten in food or medicines can sustain IgA deposition despite an apparently restricted diet.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
IgA deposits in papillae
Granular IgA accumulates at dermal papillary tips and along the junction, creating a tissue signature outside the intestine.
2
Neutrophils form microabscesses
Immune deposition recruits neutrophils into papillae, where proteases weaken the junction and create tiny subepidermal vesicles.
3
Scratching destroys morphology
Extreme itch leads to rapid excoriation of fragile vesicles, leaving crust and pigment that can obscure the underlying grouped-blister pattern.
4
Enteropathy persists silently
Small-bowel immune injury and nutrient malabsorption can continue without gastrointestinal symptoms, linking skin diagnosis to lifelong systemic management.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Symmetrical extensor itch

Intense burning itch affects both elbows, knees, buttocks, shoulders or scalp in a distribution unlike ordinary flexural eczema.

Grouped tiny vesicles

Closely clustered papules and small clear blisters create the herpetiform pattern, although excoriation often destroys them before review.

Excoriations and pigment

Crust, erosions and post-inflammatory hyperpigmentation may be the only visible evidence when scratching is vigorous or erythema is subtle.

Silent enteropathy

Absence of diarrhoea, weight loss or anaemia does not exclude coeliac-associated intestinal injury and long-term complications.

Nutrient-deficiency clues

Pallor, glossitis, mouth ulcers, neuropathy, low weight or bone pain suggests iron, folate, B12, vitamin D or calcium consequence.

Dapsone toxicityRed flag

Cyanosis, dyspnoea, jaundice, dark urine, fever, mouth ulcers, bruising or widespread rash while taking dapsone requires urgent cessation and investigation.

Red flags requiring action

Rapidly blistering or painful skin, extensive mucosal disease, fever, weight loss, persistent diarrhoea, severe anaemia, neurological symptoms or dapsone toxicity is not routine dermatitis herpetiformis follow-up and needs urgent assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Direct immunofluorescence of normal perilesional skinFirst step
Why
Detect the characteristic IgA deposits while avoiding excoriated, inflamed tissue that has lost them.
Interpretation and limitations
Granular IgA at dermal papillary tips or along the junction is diagnostic in a compatible eruption; negative testing after wrong-site biopsy or gluten withdrawal may need specialist repeat.
02
Lesional routine histology
Why
Show neutrophils in dermal papillae and a subepidermal blister while excluding mimics.
Interpretation and limitations
The pattern supports but is not specific for dermatitis herpetiformis, so routine histology cannot replace direct immunofluorescence.
03
Total IgA and IgA tissue transglutaminase
Why
Assess coeliac autoimmunity and detect IgA deficiency that changes test selection.
Interpretation and limitations
Test while eating gluten; use IgG tTG or deamidated gliadin peptide when IgA deficient and refer positive or strongly suspected disease to gastroenterology.
04
Gastroenterology assessment and duodenal biopsy
Why
Confirm and stage gluten-sensitive enteropathy when the current adult coeliac pathway requires tissue.
Interpretation and limitations
Specialists apply current BSG criteria for selected no-biopsy diagnosis or sample bulb and distal duodenum because changes can be patchy.
05
Deficiency and bone profile
Why
Identify systemic consequences of enteropathy even when bowel symptoms are absent.
Interpretation and limitations
Check FBC, ferritin, folate, B12, vitamin D, calcium and liver profile and assess bone-density need from age, fracture and malabsorption risk.
06
Dapsone safety baseline
Why
Reduce predictable haemolytic, methaemoglobin, marrow and organ toxicity.
Interpretation and limitations
Obtain G6PD, FBC with reticulocytes, liver and renal function; deficiency raises haemolysis risk but a normal G6PD result does not remove routine haemolysis.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Scabies

Nocturnal household itch, burrows, genital, wrist and finger-web distribution and positive scraping favour infestation over symmetrical extensor IgA disease.

Excoriated eczema

Flexural or exposure-shaped dermatitis with barrier dryness and no granular IgA may resemble scratched dermatitis herpetiformis.

Bullous pemphigoid

Larger tense bullae and urticarial plaques in later life with linear IgG or C3 distinguish pemphigoid from papillary granular IgA.

Linear IgA bullous dermatosis

Annular vesicle strings and smooth linear IgA at basement membrane indicate a separate autoimmune blistering disorder.

Prurigo nodularis

Chronic scratching produces firm nodules that can dominate the picture, but distribution and correctly sited immunofluorescence resolve an underlying trigger.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First diagnostic sequenceKeep gluten in place until evidence is securedFirst stepA symmetrical excoriated extensor eruption raises dermatitis herpetiformis.

1Document distribution, intact vesicles, treatment, diet, bowel and deficiency symptoms and photograph a fresh representative area with consent.
2While gluten is still being eaten, take normal perilesional skin for direct immunofluorescence and a separate lesion for routine histology when useful, then request total IgA and IgA tTG.
3Refer confirmed or strongly suspected disease to dermatology and gastroenterology for integrated skin, coeliac and nutritional assessment before recommending lifelong restriction.

02Disease-modifying treatmentBuild a strict nutritionally complete gluten-free dietDermatitis herpetiformis and associated gluten-sensitive disease is confirmed.

1Arrange specialist dietetic teaching on wheat, barley and rye, cross-contact, labels, oats, eating out and nutritionally adequate replacements.
2Measure and replace documented iron, folate, B12, vitamin D or calcium deficits and assess bone and vaccination needs through the coeliac pathway.
3Track skin, serology, weight and deficiencies over months and reduce dapsone only after sustained control, explaining that diet benefit is slower than drug benefit.

03Rapid symptom controlStart dapsone with intensive early monitoringItch and blistering remain clinically important while the gluten-free diet takes effect.

1Review G6PD, blood count, reticulocytes, liver and renal function, interacting medicines and pregnancy context before the first dose.
2Start 50 mg orally daily under specialist care and increase only if required, reducing promptly toward the minimum 25–50 mg daily once lesions subside.
3Check blood counts and organ tests frequently at initiation and teach urgent cyanosis, breathlessness, jaundice, fever, mouth-ulcer, bruising and rash stop rules.

04Persistent diseaseFind gluten, toxicity or a wrong diagnosisLesions continue despite a credible diet and dapsone plan or recur during dose reduction.

1Use expert dietetic review to find hidden gluten and barriers, repeat coeliac serology and check whether enough time has elapsed for dietary response.
2Reassess adherence, dose, medicine interaction and dapsone toxicity and reconsider linear IgA disease, pemphigoid, scabies and excoriated eczema.
3EscalationRepeat properly sited immunofluorescence or pursue gastroenterology reassessment when original diagnostic evidence was weak, rather than escalating indefinitely from a label.

Key medicines and prescribing safety1 treatment · regimens, roles and cautions

Rapidly suppresses neutrophilic skin inflammation and itch while a gluten-free diet slowly removes the disease driver.

Dapsone

Start 50 mg by mouth once daily and increase gradually only if required, up to the specialist maximum; once lesions subside reduce promptly to the minimum, usually 25–50 mg daily.

Check G6PD, FBC, reticulocytes, liver and renal function before treatment and frequently early. Haemolysis and methaemoglobinaemia can occur despite normal G6PD; stop urgently for cyanosis, dyspnoea, jaundice, fever, mouth ulcers, bruising, hepatitis or severe rash.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Nutrient deficiency and bone loss

Silent enteropathy can cause iron, folate, B12, calcium and vitamin D deficiency, anaemia, neuropathy and osteoporosis.

Coeliac-associated malignancy

Ongoing gluten-driven intestinal inflammation increases lymphoma and other complication risk, which falls with sustained strict dietary treatment.

Dapsone haematological toxicity

Dose-related haemolysis and methaemoglobinaemia plus rare agranulocytosis can become life threatening without symptom education and monitoring.

Dapsone hypersensitivity

Fever, rash, lymphadenopathy, hepatitis and organ involvement can develop as a severe delayed reaction requiring immediate cessation and urgent care.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Follow the local dapsone schedule for frequent FBC and reticulocytes plus liver and renal tests during initiation, after dose changes and when symptoms arise.
Ask specifically about exertional dyspnoea, blue lips, headache, fatigue, jaundice, dark urine, fever, mouth ulcers, bruising, rash and neuropathy.
Use specialist dietetic review, coeliac serology, weight and deficiency correction to monitor gluten-free treatment without equating one normal antibody result with perfect mucosal recovery.
Review bone health, vaccination and associated autoimmune disease according to the adult coeliac pathway.
Reduce dapsone toward the minimum only after sustained skin control and increase again through specialist review rather than patient-led dose cycling.
Re-biopsy a fresh correctly selected site if disease behaviour and original immunofluorescence remain discordant.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Herpetiform is geometry

The name refers to grouped vesicles resembling herpes arrangement; no herpesvirus causes the underlying gluten-linked disease.

Normal bowel symptoms mislead

Cutaneous IgA disease can coexist with silent villous injury, so absence of diarrhoea does not remove dietetic and gastroenterology care.

Normal-looking skin is diagnostic

IgA is best preserved in uninvolved perilesional skin, while an excoriated blister centre can lose deposits and produce false reassurance.

Dapsone and diet solve different problems

Dapsone rapidly controls neutrophils and itch but does not correct enteropathy, deficiency or the long-term gluten-driven immune process.

Pulse oximetry can confuse

Methaemoglobin can hold pulse saturation near the mid-eighties despite adequate arterial oxygen tension, making co-oximetry the clarifying test.

11Common pitfallsFrequent interpretation and management errors.

01
Calling the eruption herpes and prescribing antiviral treatment from the name alone.
02
Taking direct immunofluorescence from an excoriated active blister instead of nearby normal skin.
03
Advising a gluten-free diet before serology and specialist diagnostic sampling are completed.
04
Using dapsone as a substitute for a strict diet and coeliac complication assessment.
05
Starting dapsone without G6PD, blood, reticulocyte, liver and renal baseline testing.
06
Reassuring from a normal G6PD result when breathlessness, cyanosis or haemolysis develops.