Atopic Dermatitis

ATOPIC ECZEMA

Definition:

Atopic eczema is an acute, subacute, or chronically relapsing inflammatory skin disorder that is characterized by intense pruritus and dry skin, occuring predominantly in infants and children.

Epidemiology:

1. Age of onset: First 2 months of life, and by first year in 60% of patients, by 5 years of age, 85% of affected children. 30% are seen for the first time by age 5, and only 10% develop AD between 6 and 20 years of age. Rarely, AD has and adult onset. ²

2. Sex: Male > Female (Ratio 1.2:1).

3. Prevalence: Between 7% and 15% in Scandinavia and Germany ²; 3.7% in one report (Jaffar et al, Clin Exp Dermatol, 1993) in KL ¹. 27.3% in Copenhagen (Stensen, L. et al. Allergy Asthma Proc 2008).

4. 75-80% of patients have personal or family history of allergic diseases.

5. More common in social classes 1 and 11. ¹

6. Often associated with an elevated serum IgE (85%) and a personal or family history of asthma, atopic dermatitis, and or allergic rhinoconjunctivitis.

Pathogenesis: ^1,2

1. Complex interaction of skin barrier, genetic, environment, pharmacologic, immunologic, metabolic ⁸, infectious and neuroendocrine factors.

2. Defects in the epidermal barrier function and cutaneous inflammation are 2 hallmarks of AD ⁸.

3. Primary defect in the immune system.

4. Atopy is characterized immunologically by reduced cell mediated immunity, defective antibody dependent cellular cytotoxicity, decreased numbers of immunoregulatory T cells, high concentration of serum IgE, and a high incidence of igE-mediated reponses on skin testing to common inhaled antigens. ⁷

5. Type I (IgE-mediated) hypersensitivity reaction occurring as a result of the release of vasoactive substances from both mast cells and basophils that have been sensitized by the interaction of the antigen with IgE (reaginic or skin-sensitizing antibody).

6. Affected skin has increased number of phenotypically abnormal Langerhans cells that is responsible for expression of activated CD4⁺ T cells and there is increased number of high affinity receptors for the Fc region of the IgE molecule.

7. In AD, the response to common allergens results in the generation of helper T-lymphocytes Th₂ in preference to Th₁.

8. Th₁  preferentially secretes interleukin-2 (IL-2), interferon gamma and tumour necrosis factor-alpha which is responsible for induction of delayed type hypersensitivity reactions.

9. Th₂  preferentially secretes interleukins that stimulates B cells and eosinophils and induce it to switch the production of IgG and IgE and further regulate IgE production, mast cells and eosinophils.

10. In the early phase of AD, T cells with Th² cytokine profile dominate over Th1 cell which explains the decrease capacity for sensitization (Th¹ response).

11. The enhanced severity of cutaneous viral infection may also be due to a decreased Th¹ response.

Triggering and aggravating factors: ¹

1. Irritants: Wool, soap, disinfectant (chlorine, occupational irritants, cigarette smoke).

2. Contact allergens: Ingredient in skin care products, topical preparation including corticosteroids, clothing, airborne allergen.

3. Aeroallergens: House dust mites, pollens, pets, moulds.

4. Food: Eggs, peanuts, milk, fish, soy and wheat.

5. Microbial organisms:

a. Staphylococcus aureus (90%).

b. Pityrosporum ovale.

6. Sex hormones: Menstruation, pregnancy, parturition and menopause may be associated with exacerbations.

7. Stress factors.

8. Climate.

9. Others: Antigen exposure, sweating, excessive bathing, UV exposure, low air humidity and cold winds.

Risk factors:

1. Chromosome studies have suggested that the trait for atopy may be inherited via a maternal gene located on chromosome 11. ⁷

2. Clinical studies demonstrate a higher risk for atopy if a child's mother rather than father has atopy ⁷.

3. In one study (Kalliomaki et al, Lancet 2001), administration of a probiotic containing a Lactobacillus strain prenatally to pregnant women who had at least one first-degree relative (or partner) with AD, and postnatally for six months to their infants, resulted in a significant reduction in the frequency of atopic disease in the children compared with administration of placebo (23% versus 46%).

4. Exclusive breast feeding during the first three months of life also has been associated with a lower incidence of AD during childhood in children with a family history of atopy ⁷.

Clinical features: ^1,2

1. Symptoms: Dry skin, prutitus  (sin qua non of AD).

2. Other symptoms of atopy: Allergic rhinitis (sneezing, rhinorrhea, obstruction of nasal passages), conjunctival and pharyngeal itching, and lacrimation.

3. Physical signs:

a. Acute: Erythematous patches, papules, and plaques with or without scale. Skin edema. Vesicles/erosions (scratching). Oozing erosion/crusting (infection).

b. Chronic: Lichenification, follicular lichenification, fissures, alopecia (lateral 1/3 of eyebrows), periorbital pigmentation. Characteristic infra-orbital fold in eyelids (Dennie-Morgan sign).

4. Distribution: Predilection for the flexures, front and sides of the neck, eyelids, forehead, face, wrists, and dorsa of the feet and hands. Generalized in severe disease.

5. Other features associated with AD: Lower threshold for pruritic stimuli, ichthyosis vulgaris, keratosis pilaris (10%), increased palmar markings and atopic pleats, white dermographism, delayed blanching, facial pallor, periorbital darkening, and characteristic personality traits (hyperactive, irritable, aggressive).

Clicical types: ¹

A. Infantile.

1. Begins between 2 and 6 months of age and clear by 2 to 3 years.

2. Characterized by intense itching, erythema, papules, vesicles, oozing and crusting.

3. Sites: Begins on cheek, forehead, or scalp; then extends to trunk or extremities, often symmetrical, patches; usually spare groin and diaper areas.

4. Children 1 year or older, lesions may appear like nummular eczema with sharply defined oval scaly eruptions on the face, trunk and extremities.

B. Childhood.

1. Usually occurs at 4 to 10 years of age, but may follow after the infantile phase.

2. Tendency toward chronicity and lichenification with dry, papular or circumscribed patches.

3. Sites: Wrists, ankles, antecubital and popliteal regions. Pruritis is frequently severe.

C. Adolescent/Adult.

1. Usually begins at about 12 years, continues onward into early 20s.

2. Eruptions are dry and thick lesions, confluent papules, and formation of large lichenified plaques.

3. Sites: Flexor folds, face and neck, upper arms and back, and dorsa of hands, feet, fingers and toes.

Diagnosic criteria:

Various validated sets of criteria have been developed over the past decades but there is disagreement about its definition. ⁴

Criteria list	Requirements (number of criteria)
Hanifin and Rajka diagnostic criteria, 1980	3 major + 3 minor (27)
Kang & Tian diagnostic criteria, 1989	1 basic + 3 minor (5)
Schultz-Larsen criteria, 1992	> 50 points (6)
Lillehammer criteria, 1994	Visible eczema + 4 minor (12)
U.K. Diagnostic criteria, 1994	Pruritus + 3 minor (6)
ISAAC questionaire, 1995	Score > 3 (7)
Japanese Dermatology Association criteria, 1995	All 3 features (3)
Criteria of Diepgen, 1996	> 10 points (8)
Millenium diagnostic criteria, 1998	Allergen-specific IgE + 2 principal (4)
Danish Allergy Research Centre (DARC), 2005	3 features (3)

*ISAAC: International Study of Asthma and Allergies in Childhood.

Hanafin and Rajka criteria:

1. Hanafin and Rajka criteria (Acta Derm Venereol, 1980) was considered useful, convincing and gold standard for AD diagnosis from many researchers and often used in clinical trials. ⁵

2. However, the list is time consuming and not manageable; therefore unsuitable for population-based studies. ⁴

Kang and Tian criteria.

1. Kang and Tian criteria (Int J Dermatol, 1987) was developed based on Hanifin and Rajka criteria, by removing items that help little in diagnosis or that do not differ between AD and controls.

2. It has been validated for Chinese population. ⁵

The UK Diagnostic criteria (William et al, Br J Dermatol, 1994):

1. The UK diagnostic criteria are the most extensively validated. ⁴

2. These simplified criteria are easy to use, take under 2 minutes per patient to apply, and do not require examinees to undress.

3. The diagnostic efficiency was similar to those of Hanifin and Rajka and of Kang and Tian in out-patients setting.

4. In pilot studies in European countries, it has been found to be suitable for implementation in both hospital-based and population-based studies, with a high sensitivity and specificity. ⁵

5. It has since been adopted for use in the guidelines for management of atopic dermatitis by Dermatological Society of Malaysia (PDM), 2000.

Major criterion:

An itchy skin condition (or parental report of scratching or rubbing in a child).

Minor criteria:

1. History of involvement of the skin creases such as folds of elbows, behind the knees, fronts of ankles or around the neck (including cheeks in children under 10 years). *[Children under 4 years in PDM guidelines]

2. A personal history of asthma or hay fever (or history of atopic disease in a first-degree relative in children under 4 years).

3. A history of a general dry skin in the last year.

4. Visible flexural eczema (or eczema involving the cheeks/forehead and outer limbs in children under 4 years).

5. Onset under the age of 2 years (not used if child aged under 4 years).

**Fulfilment of the major criterion plus three or more minor criteria leads to the diagnosis of atopic eczema. ⁵

Differential diagnosis: ²

1. Seborrheic dermatitis, contact dermatitis, nummular dermatitis, scabies, psoriasis, cutaneous T-cell lymphoma, HIV-associated disease, graft-versus-host disease, and familial keratosis pilaris.

2. Others: Letterer-siwe disease, acrodermatitis enteropathica, Wiskott-Aldrich syndrome, hyper IgE syndrome, ataxia telangiectasia and phenylketonuria.

Course and prognosis:

1. 60% of patients develop the condition by 1 year of age and 90% by 5 years.

2. The course is characterized by exacerbations and remissions.

3. Clearance with remission occurs in 65-90% by age 15 years according to different series with some as low as 30%.

4. Adult onset AD often runs a more chronic and severe course.

5. 30% to 50% of patients develop asthma and/or hay fever.

Complications:

1. Infections.

a. Bacterial: Staphylococcal and Streptococcal infections.

b. Viral: Herpes simplex (Kaposi's varicelliform eruption), molluscum contagiosum, viral warts.

c. Others: Dermatophytes, candida infections, scabies.

2. Erythroderma (Exfoliative dermatitis).

3. Eyes:

a. Cataracts (up to 10% of severe adolescent and adult cases, usually anterior subcapsular (cf steroid induced-posterior subcapsular).

b. Keratoconus.

c. Vernal conjunctivitis with papillary hypertrophy or cobblestoning of upper eyelid conjunctiva.

4. Psychosocial.

Laboratory examinations: ²

A. Bacterial culture.

1. Colonization with S. aureus is very common in the nares and in the involved skin.

2. 90% of patients with severe AD are secondarily colonized/infected.

B. Viral culture: rule out herpes simplex infection in crusted lesions (eczema herpeticum).

C. Blood studies: Increased IgE, eosinophilia, RAST (suspected food sensitivity).

D. Dermatopathology.

1. Various degree of acanthosis with rare intarepidermal intercellular edema (spongiosis).

2. The dermal infiltrate is composed of lymphocytes, monocytes, and mast cells with few or no eosinophils.

MANAGEMENT OVERVIEW:

1. General.

2. Pharmacological.

3. Psychological.

General:

1. Education.

2. Avoidance of aggravating factors.

Pharmacological treatment:

A. Topical.

1. Emollients.

2. Astringents.

3. Topical antibiotics.

4. Topical corticosteroids.

5. Topical calcineurin inhibitors (Tacrolimus, Pimecrolimus).

6. Combinations (Corticosteroids and antibiotic).

B. Systemic.

1. Systemic corticosteroids.

2. Cyclosporins.

3. Azathioprine.

4. Interferon.

5. Other immunosuppresants (case reports, no controlled trials): Mycofenolate mofetil, Methotrexate.

6. Other adjunctive: Anti-histamine, anti-microbials.

7. Other investigational (case reports): Anti-IgE monoclonal antibody Omalizumab, anti-CD11A monoclonal antibody Efalizumab ⁷ , Allergen immunotherapy (unproven), Extracorporeal photopheresis (anecdotal reports) ³.

C. Phototherapy.

D. Alternative.

1. Evening Primose Oil (EPO).

2. Traditional Chinese Herba Therapy (TCHT).

3. Probiotic therapy with Lactobacillus (insufficient evidence). ⁷

4. Oral essential fatty acid (insufficient evidence) ⁷.

Psychological treatments:

Behavioral therapy.

TOPICAL TREATMENTS:

1. Mainstay of treatment in AD.

2. Avoidance of irritants e.g. Soap and detergents is also important.

3. Aqueous cream, vaseline, emulsifying ointment and emollient soaps may be used.

Emollients:

1. Aim: Reduce transepidermal water loss.

2. When to apply: Best applied after bath.

3. Examples: Aqueous cream, ung emulsificans, urea cream. Generally, greasier emollients work better, subject to patient acceptability.

Astringents:

1. Aim: Dry up lesions during vesicular or exudative stage.

2. Examples:

a. Potassium permanganate 1:10 000 dilution, or dilute till pink in colour.

b. Normal saline, a more costly alternative.

3. How to use:

a. Soak affected parts in selected solution for 10 to 15 minutes each time, few times a day depending on severity and response.

b. Cool compresses.

Topical steroids:

A. Use as main anti-inflammatory agent.

1. Choice depends on a balance between efficacy and side effects.

2. Generally, more potent steroid has more side effects. However, newer preparations have improved therapeutic ratio.

3. Ointment form is more potent than cream form.

4. Most are applied BD, newer ones OD.

5. Potent steroids can be used initially but only for short term of intermittent basis.

6. Occlusive therapy may be used to increase the potency of steroids in recalcitrant cases.

7. Avoid sudden discontinuation to prevent rebound phenomenon.

8. Use milder steroids for children, face, flexurals, scalp or larger surface areas. Potent steroids may be used on palms and soles.

9. Use emollients to spare corticosteroids.

10. “Steroid holidays” may be required to avoid tachyphylaxis.

B. Amount to be used:

1. The amount of very potent steroid used should be less than 50g per week for an adult (Class IV according to potency grading system for topical corticosteroids by Miller & Munro).

2. A rough guide to estimate the amount of topical application required:

a. 1% of total BSA requires 0.25g.

b. Use rule of 9 to estimate amount required for large areas.

c. The finger-tip unit (F.T.U.) is a convenient way of indicating to patients how much of a topical steroid shoud be applied to the skin at any one site.

d. 1 FTU is the amount of steroid expressed from the tube to cover the length of the flexor aspect of the terminal phalanx of the index finger.

Surface to be covered	Amount in F.T.U
1 Hand/foot/face	1
1 Arm	3
1 Leg	6
Front and back of trunk	14

C. Choice of formulations:

1. Lotion for exudative lesions.

2. Cream for dry lesions.

3. Ointment for very dry lesions.

4. Lotion or gel for scalp.

D. Side effectss:

1. Local: Skin atrophy, telangiectasia, purpura, striae, acne.

2. Rebound phenomenon.

3. Hirsutism.

4. Secondary infections e.g. Bacterial, viral, fungal.

5. Perioral dermatitis.

6. Sensitization to vehicle or even steroid itself.

7. Systemic: Adrenal axis suppression, Cushing's syndrome.

Topical calcineurin-inhibiting ascomycins (Tacrolimus, Pimecrolimus):

1. Reduce ultraviolet light B-induced DNA damage in animal models and human skin.

2. Tacrolimus has shown notable anti-inflammatory effects, being superior to corticosteroids, especially in young children and has efficacy on facial and non-facial lesions. ⁶

3. Topical calcineurin inhibitors have demonstrated to be efficacious in several randomized, controlled trial, and, unlike topical corticosteroids, do not cause skin atrophy.

4. For this reason they may be particularly useful on the face, neck, and in skin folds.

5. Transient burning, erythema, and pruritus are the most common adverse effects ⁷.

Safety: ⁷

1. Although in controlled trials the topical calcineurin inhibitors have appears to be safe in adults and children, in 2005, based upon case reports, animal studies, and the known risks with systemic calcineurin inhibitors, thye FDA issued warnings about a possible link between topical calcineurin inhibitors and cancer, and in 2006 placed a “black box” warning on the prescribtion information for these medications.

2. However, no definite causal relationship has been established.

3. While further study is underway, the FDA has made the following recommendations:

a. Use these agents as second-line therapy in patients unresponsive to or intolerant of other treatments.

b. Avoid the use in children younger than two years of age.

c. Use these agents only for short periods of time and use the minimum amount necessary to control symptoms.

d. Avoid continuous use and avoid the use in patients with compromised immune system.

SYSTEMIC TREATMENTS:

Systemic steroids:

1. Has little place in management of most patients.

2. Reserved for exceptionally stubborn cases in view of their side effects and should be discontinued as soon as possible.

3. In some with a severe flare or to tide over an acute crises, a short course may be given.

4. Long term steroids is strongly discouraged because of associated toxicity, especially in infants and children.

Cyclosporin A: ^1,3

1. Cyclosporin is a potent immunosuppressive drug that acts primarily on T cells by suppressing cytokine transcription.

2. The drug binds to cyclophilin, an intracellular protein, and this complex, in turn, inhibits calcineurin, a molecule required for initiation of cytokine gene transcription. ³

3. The efficacy in atopic dermatitis has been demonstrated in several double-blind, controlled, crossover studies in adults and children. ¹

4. Indications: Limited to treatment of very severe, therapeutically resistant cases and under supervision of an experienced dermatologist in view of its toxicity.

5. Discontinuation of treatment may result in rapid relapse of skin disease, although some patients may have sustained remission.

A. Contraindications:

1. Concomitant therapy with nephrotoxic or cytotoxic agents.

2. Concomitant immunosuppressive or radiation (UVB and PUVA).

3. Previous or concomitant malignancies.

4. Infections of any type.

5. Primary or secondary immunodeficiency.

6. Drug or alcohol abuse.

7. Abnormal renal function.

8. Uncontrolled hypertension.

9. Uncooperative patients.

B. Dosage:

1. 2.5mg/kg to 5mg/kg per day for 6 to 8 weeks.

2. Various oral-dosing regimens have been used with success in short-term and long-term (1 year) use, whereas some authorities advocate body-weight-independent daily dosing of adults with 150mg (low dose) or 300mg (high dose) daily of cyclosporin microemulsion.

C. Side effects:

1. Nephrotoxicity.

2. Hypertension.

3. Gradual recurrence on stopping.

4. Malignant neoplasm.

5. Hyperlipidaemia.

6. Others: Paraesthesia, tremor, headache, hypertrichosis, gingival hyperplasia, gastro-intestinal disturbances, fatigue, joint pains, myalgia, breast tenderness, pseudolymphoma, hepatotoxicity, mild anaemia, hyperuricaemia, hypermagnesemia, hyperkalemia.

D. Monitoring:

1. Baseline: Renal profile, Mg²⁺,uric acid, LFT, FLP, UFEME, GFR (ideally be done, as serum creatinine is an unreliable indicator of decreased renal function).

2. First 3 months (every 2 weeks): Renal profile, BP.

3. Subsequently (monthly): Renal profile, BP.

4. Periodically: Renal profile, LFT, FLP.

5. If serum creatinine rises beyond 30% of baseline level, CyA dosage should be reduced for one month and continued if it stays below this level, otherwise it should be discontinued.

6. If hypertension develops (diastolic > 95mmHg), it should be treated with calcium channel antagonists such as Nifedipine or Isradipine but not Diltiazem or Veerapamil (interference with CyA blood levels.

7. Diuretics should not be used.

8. Withdraw CyA if hypertension cannot be controlled with these measures.

E. Drug interactions:

1. Nephrotoxic drugs: Aminoglycosides, Amphotericin B, Ciprofloxacin, Trimethoprim.

2. NSAIDs: Potentiates adverse effects on renal function.

3. Lovastatin and colchicine: Increased risk of muscular toxicity.

4. Agents increasing blood CyA levels: Ketoconazole, Erythromycin, Doxycycline, OCP, CCB (Diltiazem, Nicardipine, Veerapamil).

5. Agents decreasing blood CyA levels: Phenobarbitone, Phenytoin, Carbamazepine, Rifampicin.

Azathioprine: ³

1. Azathioprine is a purine analog with anti-inflammatory and anti-proliferative effects.

2. It has been used for severe AD, although no controlled trials have been reported.

3. Myelosuppression is a significant adverse effect, and thio-purinemethyl transferase (TPMT) levels may predict individuals at risk.

Interferon-γ: ³

1. IFN- γ is known to suppress IgE responses and downregulate Th2 cell proliferation and function.

2. Several studies of patients with AD, including a multicenter, double-blind, placebo-controlled trial and two long-term open trials, have demonstrated that treatment with recombinant human IFN- γ results in clinical improvement.

3. Reduction in clinical severity of AD correlated with the ability of IFN- γ to decrease total circulating eosinophil counts.

4. Influenza-like symptoms are commonly observed side effects early in the treatment course.

Mycofenolate mofetil: ³

1. Mycophenolate is a purine biosynthesis inhibitor used as an immunosuppressant in organ transplantation, that has been used for treatment of refractory inflammatory skin disorders.

2. Open-label studies report that short-term oral mycofenolate mofetil, 2 g daily, as monotherapy results in clearing of skin lesions in adults with AD resistant to other treatment, including topical and oral steroids and psoralen and UVA light.

3. Cautious adverse effects: Dose-related bone marrow suppression, herpes retinitis (rare).

4. It should be discontinued if patients do not response within four to eight weeks.

Phototherapy: ¹

1. PUVA, UVB, UVB+PUVA.

2. Recommended to be used only by credentialled dermatologists/physicians.

3. UVB phototherapy uses either broadband or narrowband, while photochemotherapy (PUVA) requires the ingestion of a psoralens before UVA exposure.

4. It has been demonstrated to be effective in the treatment of AD in both adults and children, although the response rate and duration of remission are not as good as in psoriasis.

A. Indications:

1. Severe atopic dermatitis, so as to be disabled educationally, physically, socially and/or emotionally by their eczema.

2. Failure to respond to intensive topical therapy with emollients and topical steroids of appropriate potency.

3. Preferable as an alternative to oral steroids in severe cases of AD or for a steroid sparing effect for those already on steroids.

B. Benefits:

1. Amelioration of prutitus with restoration of normal sleep pattern.

2. Reduction of topical steroid use or a 'holiday' from steroid.

3. Reduction in severity of AD.

C. Potential side effects:

1. Short term: Skin dryness, erythema, intensification of itching, burning, herpes labialis.

2. Long term: Possible increased risk of skin cancer, however less likely with UVB when compared with PUVA.

D. Methodology:

1. UVB (broadband or narrowband):

a. Initial dose usually 70% of MED.

b. Subsequent dose increases by 20% (if no erythema or burning).

c. Frequency or irradiation: 2-3 times per week.

2. Photochemotherapy (PUVA):

a. Oral medication: 8-methoxypsoralen (8-MOP) at 0.6mg/kg body weight given 2 hours prior to UVA dose.

b. UV protective eye glasses to be worn after ingestion of psoralen.

c. Frequency of treatment: 2-3 times per week.

E. Precautionary measures:

1. At each visit before the UV dose is given, always check for erythema, intensification of itchiness, burning sensation or sleep disturbance.

2. An ophthalmological assessment is mandatory before starting treatment and after every 50 treatments in case of PUVA.

3. UVA protective eye glasses is to be worn once psoralens have been ingested and used till sunset.

4. Reduce further exposures to sunlight after the phototherapy.

5. PUVA therapy is contraindicated in pregnancy.

ALTERNATIVE TREATMENTS:

Evening Primrose Oil (EPO): ¹

1. The efficacy in Ad is controversial.

2. Some studies have shown improvements in severity of asthma, but others have failed to show any improvement.

Recommendations:

1. EPO appears to be safe, but because of its cost, and its limited efficacy, EPO is not a first line treatment but may be tried in difficult cases.

2. Doses should be 2-4gm in children and 6-8gm in adults.

3. Brand-named EPO as quoted in clinical trials should be used as the results cannot be extrapolated to generic brands of EPO.

4. If no improvement is seen within 4 months of EPO supplementation, therapy should be abandoned.

Traditional Chinese Herbal Therapy (TCHT): ¹

1. In 1992, TCHT (marketed as Zemaphyte in UK) was shown to be effective in refractory AD in children and adult.

2. A one-year follow up of treated children found that 50% enjoyed at least 90% reduction in eczema scores and a smaller percentage showed lesser degrees of improvement. However, in 2 children, there was one occasion, elevation of liver enzymes (AST) to 7-14 times normal, returning to normal 8 weeks later.

3. Recent work suggests that TCHT may have immunomodulatory, anti-inflammatory or sedative effects, targeting various immunological parameters involved in the pathogenesis of AD.

4. The beneficial response of TCHT, however, is temporary, and effectiveness may wear off despite continued treatment.

5. The possibility of hepatic toxicity, cardiac side effects, or idiosyncratic reactions remains a concern.

Recommendations:

1. The 10 herbs in Zemaphyte are available locally but these are not subject to strict quality control to exclude toxic contaminants such as arsenic.

2. It is probably premature to routinely recommend TCHT in view of possible toxicity from Zemaphyte constituents and unwanted contaminants.

Severity and response to treatment assessment:

1. SCORAD.

2. 

References:

1. Dermatological Society of Malaysia. Consensus Guidelines on the Management of Atopic Dermatitis.

2. Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology, 5^th ed. McGraw Hill. 2005, pg 33-41.

3. Fitzpatrick's Dermatology in General Medicine, 7^th ed. McGraw Hill. 2008, pg 146-158.

4. E.E.A. Brenninkmeijer, M.E. Schram, M.M.G. Leeflang, J.D. Bos, Ph.I. Spuls. Diagnostic criteria for atopic dermatitis: a systematic review. Bristish Journal of Dermatology, 2008, 158:754-765.

5. H. Gu, x.S. Chen, Y. Yan, H. Jing, X.Q. Chen, C.G. Shao, G.Y. Ye. Evaluation of diagnostic criteria for atopic dermatitis: validity of the criteria of Williams et al. in a hospital-based setting. British Journal of Dermatology, 2001;145:428-433.

6. Congress report: Treatment of Atopic Dermatitis. A review of News Presented at the 12^th Congress of the European Academy of Dermatology and Venerology (October 15-18, 2004 Barcelona, Sapin). [http://www.accessdermatology.com]

7. Up To Date (15.1). Atopic dermatitis. February 2007.

8. Krakowski, A.C., Eichenfield, L.F., Dohil, M.A. Management of Atopic Dermatitis in the Pediatric Polpulation. Pediatrics, 2008;122:812-824.