HFMD: What You Should Know
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Chronic hand eczema is a common and often debilitating condition. Alitretinoin, a 9- cis -retinoic acid and pan-retinoic acid agonist, is a new and effective systemic treatment for chronic hand eczema, which provides another treatment option.
Even higher rates of remission can be obtained with a longer duration of treatment. Alitretinoin has a favorable overall profile of adverse effects; however, female patients who are at risk of becoming pregnant should follow a strict pregnancy-prevention program due to the teratogenic effects of this drug.
Eczema or dermatitis are broad terms to describe an inflammatory skin condition, which may be dry, red, itchy, and flaky. Dermatitis is the most common skin disease affecting the hands. A number of causes of CHE are recognized, which are often multifactorial. These include atopic dermatitis, irritant contact dermatitis, and allergic contact dermatitis. Common irritants include organic solvents, detergents, and water itself. It should be remembered that both irritant and allergic contact dermatitis are more common in atopic individuals.
There are many different subtypes of hand eczema, with varying clinical presentations, which can make a precise diagnosis challenging. In addition to the classification based on etiology, CHE can be classified depending on localization and morphology; the latter includes hyperkeratotic and pompholyx variants. Overall, seven distinct subdiagnoses have been agreed upon in a recent European study.
Diagnosis of CHE is usually clinical, and is based on history, including personal and family history of atopy, occupational factors, hobbies, and skin-care products used. Physical examination should include thorough inspection of appearance and distribution of dermatitis on the hands, as well as affected areas elsewhere on the body. In particular, feet should be carefully examined, as feet are often affected in patients with different types of CHE.
Important investigations to consider are bacterial swabs for culture to look for secondary infection. Fungal skin scrapings should be considered if the feet are involved or if only one hand is affected. Differential diagnosis may include psoriasis, dermatophyte infections, scabies, lichen planus, dermatomyositis, pityriasis rubra pilaris, and rarely mycosis fungoides.
If diagnosis is in question, a skin biopsy may be considered. Patch testing is recommended if an allergic contact dermatitis of delayed type IV hypersensitivity reactions is suspected. In addition, products should be tested if appropriate. If allergic contact dermatitis of type I hypersensitivity reactions is assumed, radioallergosorbent or skin-prick tests are employed. As with most chronic diseases, there is a stepwise approach to management. Basic skin care is the cornerstone of management, which includes avoidance of common irritants, discontinuing skin-care products that may be an irritant eg, aqueous cream , and use of personal protective equipment, such as gloves.
Gloves made of plastic or polyvinyl chloride material are preferable to rubber in order to avoid accelerator chemicals. Hands should be kept well moisturized with frequent application of a suitable emollient, especially after washing hands.
Moisturizing soap substitutes should be routinely used, and ointments are preferred to creams and lotions in this setting. It is quite important to diagnose whether the patient is suffering from irritant contact dermatitis or allergic contact dermatitis, and in the latter it is imperative to determine the precise relevant allergen s involved.
The patient should be meticulously educated to avoid such allergen s in future, because even very small quantities of these substances can trigger allergic contact dermatitis. Topical corticosteroids are used as the next step up. As with emollients, ointments are preferred over creams, due to increased absorption and efficacy. Moderately potent topical corticosteroids are routinely used, but often the strength of topical corticosteroids has to be upgraded to potent and very potent preparations.
Furthermore, application under occlusion makes topical corticosteroids more effective. Unfortunately, severe CHE is often resistant to even very potent topical corticosteroids, and side effects with longer-term use, such as skin atrophy, limit their use for long-term treatment. Topical calcineurin inhibitors tacrolimus ointment or pimecrolimus cream can be used as maintenance therapy, but generally they are more effective when used on face and skin folds areas compared to hands and feet.
Phototherapy is reserved as second-line treatment for CHE. Although high-dose Grenz irradiation has been associated with the development of nonmelanoma skin cancers, Grenz-ray therapy is still considered by some authorities as a safe treatment modality when administered according to the guidelines. If the aforementioned measures are not sufficient, systemic therapy should be considered.
Short-term courses of corticosteroids are sometimes used for acute flare-ups, although their side-effect profiles make them unsuitable for long-term use. Notably, oral corticosteroids usually act faster than topical corticosteroids, and thus may be very useful when it is important to bring severe CHE under control quickly.
A number of steroid-sparing systemic agents have been used for hand eczema, including azathioprine, cyclosporine, and methotrexate; however, the only systemic therapy currently licensed for use for CHE is alitretinoin. All three drugs may also cause bone marrow suppression, and in addition azathioprine and methotrexate are hepatotoxic, whereas cyclosporine may cause irreversible renal impairment.
Furthermore, methotrexate is a teratogenic medication. Alitretinoin 9- cis -retinoic acid is an endogenous retinoid related to vitamin A. This distinction may explain why alitretinoin is effective in control of CHE while other retinoids isotretinoin, acitretin, bexarotene are not. The assumption is that binding to both receptors is required for control of CHE. Although the exact mechanism of action of alitretinoin in CHE is yet to be elucidated, it is believed to involve the regulation of the expression of genes that control cellular differentiation and proliferation.
It has also been shown to have immunomodulatory and anti-inflammatory effects by chemokine-induced leukocyte recruitment and inhibition of dendritic cell-mediated T-cell activation. Most side effects of alitretinoin have been shown to be reversible, dose-dependent, and consistent with side effects for other retinoids. The standard dose of alitretinoin is 30 mg once daily OD , reducing to 10 mg OD if intolerable side effects are encountered. A dose of 10 mg OD from the beginning may be considered in at-risk patients, eg, patients with diabetes mellitus.
The most common side effect of alitretinoin is headache. Sensitivity to sunlight is a common problem, and patients should avoid excessive sunlight, use high sun protection-factor sun creams, and avoid sun beds. Dryness of the lips, skin, and mouth, anemia, flushing, and erythema are the other most frequent adverse effects. However, dryness of the lips and skin appears to be a very rare side effect. Most clinicians will agree that dry skin and lips are not a problem with this drug unlike acitretin and isotretinoin.
Decreased night vision has been reported. No psychiatric adverse effects have been found. Increases in serum cholesterol and triglycerides and a decrease in serum thyroid-stimulating hormone sometimes occur, but to date have not led to discontinuation of alitretinoin in the setting of clinical trials.
Alitretinoin, like other retinoids, is teratogenic. Female patients of a childbearing age who are at risk of becoming pregnant should be clearly counseled and started on a pregnancy-prevention program prior to commencement of alitretinoin. At least one reliable method of contraception, ideally combined with a second method of contraception, should be commenced 1 month before starting alitretinoin and continued without interruptions during the whole period of treatment and for 1 month after stopping alitretinoin.
Pregnancy testing should be done prior to the commencement of alitretinoin and subsequently every month during the treatment, as well as 1 month after discontinuation of the medication. Prescriptions should be limited to 30 days of treatment, pregnancy testing should happen on the same day as prescribing, and dispensing should happen within a maximum of 7 days of the prescription being issued.
Patients should not give blood during and for 1 month after their treatment, due to the risk of the recipient being a pregnant female. Overall, because of potential side effects, the ideal target population for alitretinoin might be nonatopic nonobese male patients with CHE.
In addition, alitretinoin reduces the plasma concentration of simvastatin. In practice however, the effects of the interrelations appear to be small. Drug interactions with hormonal contraceptives should also be taken into account if they are being used. Due to the known interaction of other retinoids with tetracyclines causing benign intracranial hypertension, tetracyclines should not be used in combination with alitretinoin. A total of 1, patients with severe refractory CHE in dermatology outpatient clinics were randomized in a 1: All patients were told to apply an emollient frequently, but no other medication for CHE was allowed.
All responders were followed up for a further 24 weeks to assess relapse, when no additional treatment was allowed. The response was dose-dependent Table 1. The response was evident after 2 months of treatment, and reached a plateau after 6 months of treatment. Patients with all types of eczema responded; however, the response varied depending on the type of CHE: However, two-thirds of patients who achieved clear or almost-clear status remained in remission 6 months later.
Response of patients with chronic hand dermatitis to alitretinoin in the Benefit of Alitretinoin in Chronic Hand Dermatitis study. A second randomized double-blind placebo-controlled trial was carried out in patients with severe CHE who had previously responded to treatment in the BACH study and who had relapsed within the week follow-up period.
Patients who had responded to placebo in the BACH trial were allocated to the placebo group again. Overall results showed that retreatment was well tolerated and effective, with highest response rates seen with a 30 mg dose and adverse events similar to those in the first study. An open-label trial was also carried out to study an extended treatment with a further 12—24 week course of oral alitretinoin 30 mg in patients who did not respond to initial therapy in the BACH trial.
All patients received 30 mg alitretinoin, irrespective of their treatment in the BACH trial. This study demonstrated that a significant proportion of patients who initially failed to respond to either 10 or 30 mg of alitretinoin could still benefit from an extended course of treatment for a further 12—24 weeks. In this trial, alitretinoin was found to be well tolerated for up to 48 weeks.
However, because these trials were double-blinded, it was not possible to use a flexible dose to minimize adverse effects, as would usually happen in clinical practice. An open-label study assessing the safety and efficacy of alitretinoin in patients with severe CHE unresponsive to topical corticosteroids studied patients with severe CHE unresponsive to topical corticosteroids.
Results of a visual analog scale and a categorical scale for pruritus also provided supportive evidence for alitretinoin efficacy. Hyperkeratotic CHE showed the highest response rate The severity of CHE is defined as severe on the PGA in combination of a dermatology quality-of-life index score of 15 or more.
NICE recommends to stop treatment if 1 there is an adequate response, 2 there is still severe disease at 12 weeks of treatment, or 3 an adequate response has not been achieved by 24 weeks.
Alitretinoin should be prescribed only by dermatologists or physicians with experience of managing CHE and monitoring systemic retinoids. Alitretinoin has also been reported to be helpful in other dermatological conditions beyond CHE. A case series of seven patients showed that alitretinoin may be effective to treat palmoplantar pustular psoriasis.
According to case reports, systemic alitretinoin may also be effective in lichen planus, 25 Hailey—Hailey disease, 26 pityriasis rubra pilaris, 27 Darier disease, 28 — 29 alopecia areata, 30 and dissecting cellulitis of the scalp.
CHE is a common skin condition that can be distressing and debilitating for a significant proportion of patients. While good hand care, frequent use of emollients, and a judicious use of topical steroids are essential part of its management, systemic treatment is necessary in a number of patients.
Patch testing should be considered in patients who fail potent topical corticosteroids.
Potency Steroid Cream, Immune Globulin Injection, Gram stain testing. Illustration.
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Laden Sie den lizenzfreien Vektor "Potency Steroid Cream, Immune Globulin Injection, Gram stain testing. Illustration. Hand, foot, and mouth disease. Grunewald AM, Gloor M, Gehring W, Kleesz P () Barrier creams of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti- inflammatory drug. () Acyclovir in the treatment of hand-foot-and-mouth disease. 25 Nov Chronic hand eczema is a common and often debilitating condition. aqueous cream), and use of personal protective equipment, such as gloves. Dryness of the lips, skin, and mouth, anemia, flushing, and erythema are the other . for use in severe CHE that has not responded to potent topical steroids.