Page 642 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 44 Atopic and Contact Dermatitis 617

Patients with disseminated EH require treatment with a mofetil (a purine biosynthesis inhibitor), azathioprine (a systemic
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systemic antiviral, such as acyclovir. Recurrent cutaneous herpetic immunosuppressive agent affecting purine nucleotide synthesis
21
infections can be treated with prophylactic oral acyclovir. and metabolism), and methotrexate (a folic acid antagonist that
Superficial dermatophytosis can be treated with topical or, rarely, interferes with purine and pyrimidine synthesis). 13,19 All of these
with systemic antifungals. drugs require careful monitoring of patients for potential serious
adverse effects.
Antipruritic Agents
Pruritus is the most common and least tolerated symptom in Phototherapy and Photochemotherapy
AD. Mediators other than histamine, including neuropeptides Ultraviolet (UV) light therapy can be a useful treatment for
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and cytokines, especially IL-31, can contribute to pruritus, and chronic, recalcitrant AD. Potential long-term adverse effects
centrally acting agents, such as opioid receptor antagonists, have include premature skin aging and cutaneous malignancies. In
been shown to be effective against the itch of AD. Treatment patients with moderate-to-severe chronic AD treated with
with cyclosporine, which results in decreased transcription of a narrow-band UVB phototherapy, gene expression and immu-
number of proinflammatory cytokines, leads to rapid improve- nohistochemistry studies of both lesional and nonlesional skin
ment in pruritus in many AD patients. Monoclonal antibodies showed that Th2, Th22, and Th1 immune pathways were sup-
(mAbs) against IL-31 and its receptor are undergoing clinical pressed and that measures of epidermal hyperplasia and dif-
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trials in patients with AD, and two phase three trials of a mAb ferentiation were normalized. Clinical improvement was associated
against IL-4 receptor alpha, inhibiting signaling by IL-4 and with decrease in Th2/Th22–associated cytokines and chemokines
IL-13 significantly reduced pruritus and enhanced quality of and, importantly, normalized expression of epidermal barrier
22a
life. Systemic antihistamines and anxiolytics may be most useful proteins. UVB phototherapy has also been shown to significantly
through sedative effects and should be used primarily at bedtime decrease levels of toxin-producing S. aureus on the skin of
to avoid daytime somnolence. Short-term use of a sedative to pediatric patients with AD.
allow adequate rest may be appropriate. Treatment with topical
antihistamines and topical anesthetics should be avoided because Allergen-Specific Immunotherapy
of the potential for allergic sensitization. Allergen-specific immunotherapy (AIT; Chapter 91) has been
administered to patients with AD for many years, although there
RECALCITRANT DISEASE is a paucity of controlled data on this treatment. Based on limited
evidence, the updated Practice Parameter for AD states that AIT
Hospitalization may be effective for a subset of patients with AD and aeroallergen
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Patients who experience erythroderma, appear to have toxicity, sensitivity. A Cochrane review of randomized controlled trials
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or fail on conventional therapies may require hospitalization. of AIT in AD found that the trials were confounded by high
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Removing the patient from environmental allergens or stressors, loss to follow-up and lack of blinding. The authors were unable
intense education, and assurance of adherence with therapy to determine by subgroup analyses a particular allergen, age, or
usually result in marked clinical improvement. The patient can level of disease severity where AIT was more successful.
also undergo appropriately controlled provocative challenges to
identify potential triggering factors. Biologics and Investigational Therapies
Intravenous Gammaglobulin
Wet Wrap Therapy Because chronic inflammation and T-cell activation appear to play
Wet wrap therapy (WWT), in which a layer of wet clothing or a critical role in the pathogenesis of AD, high-dose intravenous
bandages is placed over topical corticosteroid with a dry layer immunoglobulin (IVIG; Chapter 84) could have immunomodula-
on top, can reduce inflammation and pruritus and acts as a tory effects in this disease. IVIG could also interact directly with
barrier to trauma associated with scratching. WWT can aid infectious organisms or toxins involved in the pathogenesis of
epidermal barrier recovery that persists even after this therapy AD. IVIG has been shown to contain high concentrations of
is discontinued, and clinical benefit can be demonstrated after staphylococcal toxin–specific antibodies that inhibit the in vitro
discontinuation. Overuse can result in chilling, maceration of activation of T cells by staphylococcal toxins. Treatment of severe
skin, or secondary infection. WWT should be employed for acute refractory AD with IVIG has yielded conflicting results. Studies
exacerbations of AD or for selective use in areas of resistant have not been controlled and have involved small numbers of
eczema, rather than as a maintenance treatment. The package patients. A systematic review of systemic therapies found that IVIG
inserts for topical calcineurin inhibitors recommend that they was not efficacious in the treatment of moderate-to-severe AD. 24
should not be used under occlusive dressings.
Omalizumab
Systemic Immunosuppressive Agents Treatment of patients with AD with omalizumab has mainly
Oral cyclosporine has been shown to be effective in placebo- been reported in case reports and case series, showing both
controlled studies in severe AD, although it is not approved for clinical improvement and lack of benefit. A placebo-controlled
treatment of AD in most countries. A systematic review of ran- trial of omalizumab given for 16 weeks did not show significant
domized controlled trials evaluating systemic immunomodulating clinical benefit. No specific markers have been identified that
treatments for moderate-to-severe AD found that, of 12 different define responders, although a recent study suggested that adult
interventions studied in 34 randomized controlled trials, strong patients with AD that responds to treatment have wild-type FLG
recommendations were only possible for the short-term use of mutations. In addition, patients receiving omalizumab have been
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cyclosporine. Patients need to be appropriately monitored while shown to have decreased levels of TSLP, OX40L, thymus and
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on this medication. Other systemic immunosuppressive drugs activation-regulated chemokine (TARC), and IL-9 and marked
that have been used to treat severe AD include mycophenolate increase in IL-10 compared with placebo.