Kembara Xtra - Medicine - Dermatitis Herpetiformis

Kembara Xtra - Medicine - Dermatitis Herpetiformis 
Introduction 
Dermatitis herpetiformis (DH) manifests as a symmetrical, chronic, relapsing, polymorphous, very itchy, papulovesicular eruption that typically affects extensor skin surfaces on the scalp, elbows, knees, buttocks, and back.
Genetic, environmental, and immunologic factors all play a role in the development of DH, an autoimmune disorder linked with gluten sensitivity. DH is distinguishable from other bullous illnesses by distinctive histologic and immunologic findings as well as concomitant gluten-sensitive enteropathy (GSE).
Skin system(s) impacted
An alternative name for the sickness is Duhring-Brocq disease.

Epidemiology (Prevalence and Incidence): Predominant age: most common in the fourth and fifth decades, but may present at any age; childhood DH is uncommon in most countries, although an Italian study showed 27% of patients were under the age of ten and 36% were under the age of twenty; and predominant gender: adults: male > female (1.5:1 in the United States, 2:1 worldwide); ch.
Incidence
1 in 100,000 people in the US each year
11/100,000 people in the United States have the condition, compared to 39/100,000 people worldwide.


Pathophysiology and Etiology 

Epidermal transglutaminase (eTG) 3, a keratinocyte enzyme involved in cell envelope creation and maintenance, may be the autoantigen in DH, according to available data.
The initiating event for DH is thought to be the interaction of wheat peptides with tTGs, which results in the formation of an autoantigen with high affinity for specific class II major histocompatibility complex (MHC) molecules. eTG is highly homologous with tissue transglutaminase (tTG), which is the antigenic target in celiac disease and GSE.
T cells and the humoral immune system are activated when the autoantigen is presented.
IgA anti-tTG antibodies interact with eTG to form IgA-eTG immune complexes, which are then deposited in the papillary dermis. Inflammation and microabscesses follow complement activation and neutrophil migration to the region.

Gluten applied directly to the skin does not cause the eruption, but gluten absorbed by mouth or rectum does. Skin eruption may take up to 5 to 6 weeks to appear after exposure to gluten.
This suggests that the GI system must process information.
Considered to be an immune complex-mediated illness

Genetics Strong association with combination of alleles High association with human leukocyte antigen (HLA)-DQ2 (95%), with the remaining individuals being positive for DQ8, DR4, or DR3. DRB1*03 and DRB1*05/07, DQA1*0301 and DQB1*0302, or DQA1*0501 and DQB1*0201/0202

Risk Elements 
GSE: More than 90% of those with DH will have GSE, which may not show any symptoms.
Celiac disease or DH in the family

Prevention 

A gluten-free diet (GFD) improves DH and lessens reliance on medical treatment. Additionally, GFD may lessen the chance of lymphomas brought on by DH.


Accompanying Conditions 

The most frequent disorder linked to DH is hypothyroidism, which is also linked to GSE, gluten ataxia, gastric atrophy, hypochlorhydria, and pernicious anemia.
GI lymphoma, non-Hodgkin lymphoma, hyperthyroidism, thyroid nodules, and thyroid cancer, as well as IgA nephropathy and autoimmune diseases like systemic lupus erythematosus, dermatomyositis, Sjögren syndrome, rheumatoid arthritis, sarcoidosis, Raynaud phenomenon, insulin-dependent diabetes mellitus, myas

Diagnosis 

A clinicopathologic link between the clinical presentation, histologic and direct immunofluorescence (DIF) analysis, serology, and response to treatment or dietary restriction is required for the diagnosis of DH.

Presenting History: An highly itchy eruption with papules and small vesicles that waxed and waned
GI symptoms may not exist or may not be noticed until prodded; eruption may get worse with gluten consumption.


clinical assessment 

The symmetric, clustered, erythematous papules and vesicles that characterize the typical lesions of DH are described.
Due to scratching and healing of previous lesions, erosions, excoriations, lichenification, hypo- or hyperpigmentation are more frequently observed.
Extensor surfaces of the elbows (90%), knees (30%), shoulders, buttocks, and sacrum are among the affected body parts. The scalp is usually impacted as well. Rare oral lesions exist.
Children may have purpura on their digits and palmoplantar surfaces.
Adults with related enteropathy are typically asymptomatic, with steatorrhea occurring in 20% of cases and bloating, diarrhea, or malabsorption in 10%.
Children with related enteropathy may have diarrhea, an iron shortage, and a slowed pace of growth.


Adults with linear deposition of C3 and IgG at the basement membrane zone are diagnosed with bullous pemphigoid; those with linear IgA illness are diagnosed with homogenous and linear deposition of IgA at the basement membrane zone and lack GSE.
Prurigo nodularis: wheals, angioedema, and cutaneous edema; Urticaria
- Multiform erythema
Atopic dermatitis affects children's faces and flexural areas. Scabies affects interdigital areas, axillae, and the vaginal area.

Initial test results from the laboratory and imaging

Serum IgA tTG antibodies were shown to be detectable in patients on unrestricted diets with up to 95% sensitivity and >90% specificity for DH.

Serum IgA eTG antibodies: Although not commonly available in all labs, antibodies to eTG, the main autoantigen in DH, have been demonstrated to be more sensitive than antibodies to tTG in the diagnosis of individuals with DH on unrestricted diets (95% vs. 79%).

Serum IgA endomysial antibodies (EMA): EMA is more expensive, time-consuming, and operator-dependent than tTG, but antibodies to it have a sensitivity between 50% and 100% and a specificity close to 100% in patients on unrestricted diets.


Tests in the Future & Special Considerations
Serologic evaluation of anti-tTG and anti-eTG correlates with intestinal disease involvement, and when combined with anti-EMA, may be helpful in detecting significant departures from GFD.

Patients may also be offered genetic testing for the HLA-DQ2 and HLA-DQ8 haplotypes to ascertain their hereditary vulnerability, to screen them for CD, or if the diagnosis is unclear.


Other/Diagnostic Procedures
DIF of the perilesional skin that shows distinctive granular IgA deposits in dermal papillae and/or basement membrane is the gold standard test to determine a diagnosis of DH. This essential diagnostic characteristic sets apart all other dermatologic disorders from this blistering skin condition.

A second perilesional skin biopsy should be taken from a different site in patients with high suspicion for DH and a negative DIF. Histopathology of these lesions with routine staining reveals neutrophilic microabscesses in the tips of the dermal papillae and may show subepidermal blistering.


Management: GFD is the cornerstone of treatment for DH and can result in full symptom relief.

 Usually takes 18 to 24 months of strictly following the GFD for skin lesions to clear up without further treatment.
Within 12 weeks of reintroducing gluten, lesions may return.

Drugs Despite being on GFD, DH lesions take several months to resolve up, and active lesions necessitate further care.

While medications are useful for treating symptoms right away, they should only be taken in conjunction with dietary changes.

Initial Line

The most popular drug, dapsone, is approved by the FDA for use in DH.
Symptoms normally begin to improve after the first dose of 25 to 50 mg/day on a strict GFD, which usually takes 24 to 48 hours.

It is advised to utilize the lowest effective dose and gradually titrate the dosage in accordance with the patient's response and tolerability.
One mg/kg/day (50–150 mg/day) is the typical maintenance dose, and it can be increased to 200 mg to improve symptom control.
Minor breakouts on the face and scalp are frequent, even with therapy; long-term usage in DH is not recommended.
Dapsone suppresses the skin reaction by preventing neutrophil recruitment and IL-8 release, limiting the respiratory burst of neutrophils, and shielding cells from damage brought on by neutrophil-mediated reactions. It plays no part in reducing the immunological response in the stomach or preventing IgA deposition.

 Safety measures
- Frequent side effects include hemolysis, headaches, nausea, and vomiting.
Dapsone 100 mg/day is known to cause hemoglobin levels to fall by 1 to 2 g.
- A lack of G6PD makes hemolytic stress more severe.
In patients who lack G6PD, dapsone should be avoided whenever possible.
- Doses more than 100 mg per day may result in dose-related methemoglobinemia. Cimetidine might lessen how bad this adverse effect is.
- Distal motor neuropathy risk

Watch out for the potentially fatal dapsone-induced sulfone syndrome, which can cause serious side effects include exfoliative dermatitis, methemoglobinemia, hemolytic anemia, fever, jaundice, and hepatic necrosis.
Can happen 48 hours or 6 months after therapy begins, but most frequently 5 weeks.


Child Safety Considerations
2 years: No recommended dosage has been determined.0.5 to 1.0 mg/kg/day for two years.

Category C: Safety during pregnancy has not been proved; secreted in breast milk; causes hemolytic anemia in babies; strict adherence to a GFD In order to avoid the necessity for dapsone during pregnancy, 6 to 12 months before conception should be taken into account.


Next Line
Before dapsone starts to work, symptoms can be acutely controlled using high-potency topical steroids.

FDA-approved for treatment in DH, sulfapyridine (1–2 g/day) is believed to be the active metabolite of sulfasalazine (2–4 g/day). Anorexia, vomiting, and nausea are typical adverse effects. The enteric-coated version might lessen adverse effects. Agranulocytosis, hypersensitivity responses, hemolytic anemia, proteinuria, and crystalluria are other adverse effects.

Topical steroids and third-generation antihistamines can be used to treat pruritus and itching symptoms.

Problems with Referral 

Over time, treating DH may call for interdisciplinary care that includes referring patients to registered dietitians, gastroenterologists, and dermatologists.

Further Treatments 

Topical dapsone therapy was mentioned as a possible alternative treatment or as an adjuvant to oral dapsone to reduce systemic exposure and the risk of serious adverse effects in a single case report. However, little research has been done on it.

Patient Monitoring for Continuous Care
Evaluation of GFD compliance and symptom recurrence by a doctor and nutritionist every six to twelve months
Anti-tTG, anti-eTG, and EMA serologic levels can be used to track GFD adherence.

Patients using dapsone must undergo lab testing every week for the first month, biweekly for the next two months, and then every three months for the rest of treatment.


Nutrition 
Wheat (including spelt, kamut, semolina, and triticale), rye, and barley (including malt) should be avoided.
Rice, amaranth, buckwheat, corn, millet, quinoa, sorghum, teff (an Ethiopian cereal grain), and oats are safe grains (gluten-free).
Oats are one example of a gluten-free grain that should be avoided since they can become contaminated with gluten during processing.
Resources for gluten-free starches that can be substituted for flour
– Amaranth, buckwheat, corn, millet, quinoa, sorghum, teff, rice (white, brown, wild, basmati, jasmine), and Montina are among the cereal grains.
– Arrowroot, jicama, taro, potato, and tapioca are examples of tubers.
Chickpeas, lentils, navy beans, kidney beans, pea beans, peanuts, and soybeans are examples of legumes. Almonds, walnuts, pistachios, chestnuts, hazelnuts, and cashews are examples of nuts.
- Sunflower, flax, and pumpkin seeds


Patients starting dapsone should be informed of the possibility of hemolytic anemia and the symptoms of methemoglobinemia.



If a GFD is strictly followed, DH has a favorable prognosis despite being a chronic condition.
Apparently, 10- to 15-year survival rates are comparable to those of the general population.
Remission in 10% to 15%

Skin conditions respond well to dapsone. It is normal to experience a few new lesions (2–3) every week; nevertheless, this is not cause to adjust the recommended daily dosage.
Strict adherence to a GFD reduces the need for dapsone while improving clinical symptoms. The only therapy for permanently curing GI and cutaneous disorders is GFD.
Those who adhere to a GFD may experience a reduced risk of lymphoma.

Complications 
The majority of problems are brought on by GSE, including malnutrition, weight loss, nutritional deficiencies (folate, vitamin B12, iron) and abdominal pain.

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