Pharmacological treatment of atopic dermatitis
Challenges: Management of atopic eczema
- No cure
- Patients need to be educated
- No clear cut standard therapeutic approach
- Responses to treatments vary with individuals
Frustrations experienced by both patient and practitioner
- Reduce signs and symptoms
- Obtain remission of the disease
- Obtain optimum benefits from treatment without inducing morbidity
- Improve the quality of life of patients
Difficult refractory cases should ideally be referred to an experienced
The reader should refer to guidelines published recently in the European
and American literature1,2,3
- J Allergy Clin Immunol 2006;118: 152-69
- JAAD 53 . 1 Suppl July 2005 1-11
- BJD 2003: 148(suppl . 63 ) : 3-10
The more important drugs to be used will firstly be discussed in detail
and that will be followed by a general approach to treating the different
degrees of severity of the condition, followed by a suggested algorithm.
Topical Corticosteroids (TCS) [ 1+ ; B ]
- TCSs continue to be the mainstay of atopic dermatitis treatment1,2.
- Mechanism of action : anti-inflammatory and immunosuppressive
Direct regulatory effect on gene transcription and indirect blocking
transcription factors at cellular level25,26.
Reduces the colonization of Staph aureus on the skin.12,13
- The market is saturated with different strengths and formulations
of TCSs However there are no adequate trials to suggest superiority
of one over the other.
- Potency of TCS is classified by the potential for vasoconstriction4
. Efficacy of TCS can be enhanced by halogenation of the 9-alpha position
which enhances potency and removing the hydrophilic 17dihydroxy acetone
side chain or the 16-alphahydoxy group which will increase lipophilicity.
- Guidelines for prescribing TCS are well-described16,17 .In general
only preparations that have very weak or moderate strength are used
on the face and genital area, whereas those that have moderate or potent
strength are used on other areas of the body 5. Patients should be educated
about the different steroid potencies in order to minimize untoward
- The vehicle through which the active steroid is delivered plays
an important role in absorption and can enhance its efficacy. Generally
ointments are more effective than creams, as the emollient action and
occlusive effect results in better penetration. Ointments also require
fewer preservatives so the potential for irritant and allergic reactions
is lower. Wet wraps and application under occlusion also enhance absorption
of topical steroids. A novel foam vehicle independent of relying on
the hydration of the stratum corneum ( which traditional vehicles depend
on ) for drug delivery is available in the United States24 .
- The British Association of Dermatologists recommend using topical
steroids for 10-14 days when the eczema is active, followed by “holidays
” with just emollients. The National Prescribing Centre recommends that
steroids be used in bursts of three to seven days to treat exacerbations.
This rationale can be extended to using potent TCS for a few days to
initiate control followed by use of a milder potency TCS and or emollient
7,8. Another strategy to taper the use of TCS is to reduce the frequency
of application .
- In a study using fluticasone propionate in adults with moderate
to severe eczema, twice-weekly application to affected and non-active
skin sites significantly prevented relapses once the flare settled 9.
For chronic lichenified eczema, however, frequent potent steroids are
required for much longer periods 8.
- The BNF also gives a rough guide as to how much TCS to use which
is a frequent practical problem with patients. The finger tip unit:
index finger: from distal crease to finger tip = 0.5 g. This aids monitoring
compliance and usage. There is no clear RCT (randomized controlled trials)
to suggest that the application of TCS twice a day is better than a
once daily application. Based on this it would be justifiable to use
once – daily corticosteroids as a first step in all patients with AD.
Such a policy would reduce cost, improve compliance and reduce side
- No convincing evidence to demonstrate superior clinical efficacy
of combination antibiotic / corticosteroid to corticosteroid alone.
- There is no RCT evidence to support the notion that diluting TCS
reduces adverse effects while maintaining efficacy in AD.
- The reduced efficacy of TCS is thought to be related to disease
severity rather than glucocorticoid resistance 4, 21.
- There are many challenges on the subject of TCS use, especially
in the light of steroid abuse, steroid misuse , steroid phobia and side
effects. There are as a result many publications addressing these issues
and certain recommendations as already discussed have been suggested
- Adverse effects are well documented but it is important to recognize
the side effects of skin atrophy, telangiectasia, hypopigmentation,
steroid acne, hirsutism, rosacea and contact sensitization to the steroid
itself. There is no RCT evidence to suggest that skin thinning is a
problem for correct use of topical steroids.
- Systemic effects though uncommon are the suppression of the hypothalamic-pituitary
–adrenal axis, growth retardation, tachyphylaxis, glaucoma and cataract
formation and Cushing’s syndrome15.
- Over recent years the risk of adverse effects of TCS has been reduced
by optimizing application protocols and using newer steroid preparations
with improved risk/benefit ratios eg. Prednicarbate, mometasone furoate,
fluticasone and methylprednisilone aceponate 10,11. To optimize the
beneficial effects of TCS different therapeutic schemes have been established:
intermittent use might be as effective as an initial therapy with a
high potent steroid followed by a time dependant dose reduction or change
over to a lower potent preparation. A recent systematic review identified
83 randomized controlled trials of the use of TCS in atopic dermatitis
3. Vehicle controlled studies lasting less than one month indicated
that approximately 80 % of people report good, excellent, or clear responses
with TCS, whereas 38% of persons whereas 38% of persons in control groups
reported such responses.
- The ideal TCS is difficult to create because the intracellular receptors
that are responsible for corticosteroid efficacy are also responsible
for the adverse side effects.18,19 However, recent findings that glucocorticoids
mediate their therapeutic effects through gene expression by transrepression
and transactivation has led to novel research which awaits clinical
- The judicious use of TCS would be short-term appropriate application
as initial monotherapy or in combination with other therapeutic agents
that ideally possess complementing mechanisms of action. These drugs
could be either systemic or topical agents such as newer topical calcineurin
- Hanifin JM, Cooper KD, Ho VC et al . Guidelines of care for atopic
dermatitis, developed in accordance with the American Academy of Dermatology.
J Am Acad Dermatol 2004;50:391-404
- Korting HC , Kerscher M J ,Schafer –Korting M. topical glucocorticoids
with improved benefit/risk ratio: do they exist? J Am Acad Dermatol
- Hoare C, Li Wan Po A, Williams H. Systemic review of treatments
for atopic eczema. Health Technol Assess 2004;4:1-191
- Hywel C Williams. N Eng J Med 2005;352:2314-24
- McHenry PM , Williams HC , Bingham EA . Management of atopic eczema
: Joint Workshop of the British Association of Dermatologists and the
Research Unit of the Royal College of Physicians of London Br Med J
- Management of atopic eczema in primary care, Prodigy, 2004.
- Thomas KS, Armstrong S ,Avery A etal. Randomized control trial of
short bursts of a potent topical corticosteroid versus prolonged use
of a mild preparation for children with mild or moderate atopic eczema
. Br Med J 2002;324-768
- Joanne Hague and John Berth-Jones. Current management of atopic
eczema in primary care www.escriber.com
Prescriber 5 September 2005 ,50-57
- Berth Jones J, Damstra RJ, Golsch S et al. Twicw weekly fluticasone
propionate added to emollient maintenance treatment to reduce risk of
relapse in atopic dermatitis: randomized , double blind, parallel group
study. Br Med 2003;326:1367
- Van Der Meer JB, Glazenburg EJ, Mulder PG et al. The management
of moderate to severe atopic dermatitis in adults with topical fluticasone
proprionate. The Netherlands Adult Atopic Study Group. Br J Dermatol
- Kerscher MJ ,Hart H, Korting HC. In vivo assessment of the atrophogenic
potency of mometasone furoate. Int J Clin Pharmacol Ther 1995;33:187-9
- Stalder J F ,Fleury M, Sourisse M et al . Local steroid therapy
and bacterial skin flora in atopic dermatitis. Br J Dermatol 1994;131:536-40
- Nilsson EJ, Henning CG, Magnusson J . Topical corticosteroids and
Staph aureus in atopic dermatitis Jam Acad Dermatol 1992;27:29-34
- Sidbury R, Hanifin JM . Old,new and emerging therapiesfor atopic
dermatitis Dermatol Clin 2000:18;1-11
- Hengge UR, Ruzicka MD ,Robert A et al. Adverse effects of topical
glucocorticosteroids. J Am Acad Dermatol 2006;54:1-15
- Sulzberger MB. Witten VH . Effect of topically applied compound
in selected dermatoses. J Invest Dermatol 1952;19:101-2
- Ayres PJ , Hooper G . Assessment of the skin penetration properties
of different carrier vehicles for topically applied cortisol. Br J Dermatol
- Smith EW . Do we need new and different glucocorticoids? . Curr
Probl Dermatol 1993;21:1-10
- Bodor N . Design of novel soft corticosteroids. Curr Probl Dermatol
- Schacke H , Schottelius A, Docke WD et al. Dissociation of transactivation
from transrepression by a selective glucocorticoid receptor agonist
leads to separation of therapeutic effects from side effects. Proc Natl
Acad Sci U S A 2004;101:227-32
- Ellison JA ,Patel L, Ray DW et al . Hypothalamic-pituitary -adrenal
function and glucocorticoid sensitivity in atopic dermatitis. Pediatrics
- Charman C, Williams H . The use of corticosteroids and corticosteroid
phobia in atopic dermatitis . Clinics Dermatol 2003;21 : 193-200
- Del Rosso J, Friedlander S F . Corticosteroids: options in the era
of steroid sparing therapy. J Am Acad Dermatol 2005;53:S50-8
- Huang X, Tanojo H, Lenn J et al . A novel foam vehicle for delivery
of topical steroids J Am Acad Dermatol 2005;53: S26-38
- Hughes J ,Rustin M. Corticosteroids. Clin Dermatol 1997;15: 715-21
- Norris D . Mechanisms of action of topical therapies and the rationale
for combination therapy. J Am Acad Dermatol 2005;53:S17-25
Topical Calcineurin Inhibitors (TCIs) [ 2+; C ]
- TCIs are complex macrocyclic compounds that bind to the intracellular
protein macrophilin-12 ( previously known as FK506-binding proteins)
and function as macrolactam immunomodulators, thereby inhibiting the
activity of the phosphorylase enzyme, calcineurin 15 . This results
in selective inhibition of cytokine transcription in activated T cells
without suppressing Langerhans cells 15,16.
- Pimecrolimus and tacrolimus are safe and effective in reducing the
severity of AD symptoms in children and adults.
- At present in South Africa we have pimecrolimus and not tacrolimus.
Evidence of the safety and efficacy of pimecrolimus was derived from
studies primarily in patients with mild to moderate atopic dermatitis;
tacrolimus data was derived from moderate to severe patients.
- Pimecrolimus has been studied in clinical trials in infants as young
as 3 months, as compared with tacrolimus from 2 years. Pimecrolimus
binds to cytoplasmic proteins and the resulting complex binds calcineurin,
inhibiting its ability to dephosphorylate the nuclear factor of activated
T-Cells (NF-AT). The ligand for cyclosporin is cyclophilin, whereas
pimecrolimus and tacrolimus bind macrophilin-12 also known as FK506
binding protein. Pimecrolimus selectively targets T cells and mast cells;
it inhibits T-cell proliferation as well as production and release of
IL2, IL4, Interferon gamma and TNF-alpha. Moreover pimecrolimus inhibits
mast cell degranulation. In contrast to tacrolimus, pimecrolimus has
no effects on the differentiation, maturation and function of dendritic
cells. In contrast to corticosteroids, pimecrolimus does not affect
endothelial cells and fibroblasts and does not induce skin atrophy.
Clinical trial data 43-45 have proven that pimecrolimus reduces incidence
of flares and has a significant effect on reducing pruritus; these trials
have not been performed for tacrolimus.
- TCIs provide a steroid free, anti-inflammatory topical therapy for
atopic dermatitis. In both animal and human studies both pimecrolimus
and tacrolimus demonstrated immunomodulatory activity 1. The anti-inflammatory
potency of 0.1% tacrolimus ointment is similar to a corticosteroid with
moderate potency 2 whereas 1% pimecrolimus cream is less active 3. Thus
far no trials have been published comparing pimecrolimus 1% with a mild
topical steroid. Both agents proved to be effective with a good safety
profile for a period of up to 2 years with pimecrolimus and up to 4
years with tacrolimus4,5.
- TCIs are frequently associated with a transient burning sensation
of the skin. A recent study showed pimecrolimus to show better tolerability
than tacrolimus especially with regards this topical effect 6 . TCIs
are not associated with skin atrophy and are therefore a useful treatment
for the face and intertriginous areas7 . This property can be an advantage
for the drug to be used long term. A long term study confirmed this
benefit and also concluded that prolonged use (at least a year ) of
tacrolimus ointment therapy is nonatrophogenic and additionally reverses
corticosteroid-induced skin atrophy 9 .
- Another randomized double blind study comparing pimecrolimus with
topical steroids in adults showed long-term safety and tolerability.
Comparative study between pimecrolimus and topical corticosteroids showed
that in patients requiring more extensive medication the incidents of
overall skin infections in the group receiving corticosteroids was double
that in the pimecrolimus group.
- Pimecrolimus was found to a safe drug with none of the side effects
seen with topical steroids and was also found to reduce the dependency
of patients to topical steroids10 .The percutaneous absorption of TCIs
was found to be low. A significant proportion of patients could also
be maintained without topical steroids for a year. Pimecrolimus is currently
approved by the FDA and the European medicines agency for short term
and intermittent use in mild to moderate atopic dermatitis.
- Few long term studies compare intermittent use of TCIs with intermittent
use of topical steroids. A 12 month vehicle controlled study of children
showed that early use of pimecrolimus reduced the frequency of flares
although early use of topical steroids might have shown similar benefits
- In the United Kingdom the national institute of clinical excellence
approves the use of topical tacrolimus for children older than two years
of age with moderate to severe dermatitis not controlled by topical
corticosteroids, and of topical pimecrolimus as a second line option
for resistant dermatitis of the head and neck12 . In the United States
both of these agents are approved as second line treatments, and the
site of application is not restricted for pimecrolimus.
- Tacrolimus has a favourable safety profile for up to four years.
- Generalised herpetic and molluscum infection have been observed
with TCIs but it is unclear whether there is an increased susceptibility
to viral infections with TCIs 8. TCIs are not safe to use in pregnancy
and during breast-feeding.
- Both drugs are a welcome addition to the treatment armamentarium
of atopic eczema. Both are useful for maintenance therapy after establishing
acute control of disease flares with topical steroids. On the basis
of the information available the American Academy of Dermatology Association
Task force recommends that TCIs remain available for patients with atopic
dermatitis and other inflammatory skin diseases 17 .
- The recent alert emphasizes the importance of using these preparations
only as labeled with patients well informed and when first line treatment
has failed or cannot be tolerated. Their drawbacks are expense, a burning
sensation on application, a slight increase in herpes labialis and a
lack of long term data and studies 14 . There is also a need for studying
the efficacy of TCIs in combination with other standard modalities of
Recommendations on the use of topical calcineurin inhibitors:
- Continuous long-term use of these agents in any age group should
- Application should be limited to areas of involvement only
- Pimecrolimus cream is not indicated for use in children less than
2 years of age.
- Tacrolimus ointment is not indicated for use in children less than
2 years of age.
- Only 0.03% tacrolimus ointment is indicated for use in children
2-15 years of age.
- Hultsch T, Kapp A , Spergel J. Immunomodulation and safety of topical
inhibitors for the treatment of atopic dermatitis. Dermatol 2005;211:174-87
- Ashcroft DM, Dimmock P ,Garside R at al. Efficacy and tolerability
pimecrolimus and tacrolimus in the treatment of atopic dermatitis ;
randomized controlled trials. Br Med J 2005; 330-516
- Luger T, Van Leent EJ, Graeber M et al . SDZ ASM 981 : an emerging
effective treatment for atopic dermatitis Br J Dermatol 2001;144:788-94
- Paul C, Cork M, Rossi AB et al. Safety and tolerability of 1% pimecrolimus
among infants. Pediatrics 2006;117:118-28
- Breuer K, Werfel T, Kapp A. safety and efficacy of topical calcineurin
inhibitors in the
treatment of childhood eczema. Am J Clin Dermatol 2005;6:65-77
- Kempers S, Boguniewicz M, Carter E et al . A randomized investigator
– blinded study
comparing pimecrolimus cream with tacrolimus in the treatment of pediatric
with moderate atopic dermatitis. J Am Acad Dermatol 2004;51:515-25
- Queille –Roussel C, Paul C, Duteil L et al. The new topical ascomycin
ASM 981 does not induce skin atrophy. Br J Dermatol 2001;144:507-13
- Wollenburg A ,Zoch C, Wetzel S et al. Predisposing factors and clinical
eczema herpeticum ; a retrospective analysis of 100 cases J Am Acad
- Kyllonen H , Remitz A, Mandelin JM et al . Effects of I year intermittent
with topical tacrolimus monotherapy on skin collegen synthesis in patients
dermatitis. Br J Dermatol 2004;150:1174-81
- Luger TA , Lahfa R, Folster –Holst R et al. Long term safety and
pimecrolimus cream 1% and topical steroids in adults with moderate to
dermatitis . J Dermatological Treatment 2004;15,169-78
- Wahn U , Bos JD, Goodfield M et al . Efficacy and safety of pimecrolimus
the long term management of atopic dermatitis in children. Pediatrics
- National Institute for clinical excellence . Final appraisal determination:
and pimecrolimus for atopic eczema. http: // www.nice.org.uk/pdf/P&T
FAD . Pdf
- center for drug evaluation and research.
- Kristian Thesstrup – Pedersen . Treatment strategies and compliance
for the adult patient with atopic eczema. Acta Derm Venereol 2005;Suppl
- Bornhovd E , Burgdorf WH ,Wollenberg A . Macrolactam immunomodulators
for topical treatment of inflammatory skin diseases . J Am Acad Dermatol
- Zuberbier T, Chong S. The ascomycin macrolam pimecrolimus is a potent
inhibitor of mediator release from human dermal mast cells and peripheral
blood basophils. J Allergy Clin Immunol 2001;108:275-80
- Berger T . Report of the American Academy of Dermatology Association
on the safety concerns of the use of TCI in dermatology. J Am Acad Dermatol
Antihistamines [ 0 ]
There is no clear RCT evidence to support the therapeutic value of antihistamines
in the treatment of atopic eczema.1,2 They are sometimes used for their
sedative effects and can be used as a short term adjuvant to alleviate severe
pruritus during acute flares4.
Expensive non-sedating antihistamines also seem to have no objective value
in treating atopic eczema 3. The results of studies are thus far conflicting
- Klein P , Clark R An evidence –based review of the efficacy of antihistamines
in relieving pruritus in atopic dermatitis. Arch Dermatol 1999;135:1522-25
- Munday J , Bloomfield R, Goldman M etal . Chlorpheniramine is no
more effective than placebo in relieving the symptoms of childhood atopic
dermatitis with a nocturnal itching and scratching component. Dermatology
- Wahlgren C F , Hagermark O, Bergstrom R . The antipruritic effect
of a sedative and a non-sedative antihistamine in atopic dermatitis.
Br J Dermatol 1990;122:545-51
- Kawashima M ,Tango T, Noguchi T et al . Addition of fexofenadine
to a topical steroid reduces the pruritus associated with atopic dermatitis
in a 1 week randomized, multicenter, double-blind, placebo-controlled
parallel-group study. Br J Dermatol 2003;148:1212-21
- Langelnd T, Fagertun H E ,Larsen S. Therapeutic effect of loratadine
on pruritus inpatients wuth atopic dermatitis. Allergy 1994;49:22-6
- Berth – Jones , Graham- Brown RA. Failure of terfenadine in relieving
the pruritus of atopic dermatitis: Br J Dermatol 1989;121:635-7
- Doherty V , Sylvester DG, Kennedy CT et al. Treatment of itching
in atopic eczema with antihistamines with a low sedative profile . Br
Med J 1989;298-86
Cyclosporine [ 3; D ]
- Cyclosporine is a oral calcineurin inhibitor available as 25 or
100mg soft gelatin capsules. Cyclosporine prevents T lymphocyte activation
and the transcription of IL2, which blocks the proliferation of other
- Efficacy in treating mild to moderate eczema is well established
but is restricted to case reports 7.
- The American academy of dermatology guidelines recommend the use
of cyclosporine for the treatment of severe atopic dermatitis on the
basis of the results of well designed randomized controlled trials although
the agent is not approved by the FDA for treating atopic dermatitis1.
- In general cyclosporine should be used on a short-term basis for
severe refractory atopic dermatitis 2. Maximal efficacy is observed
within two weeks, but relapses following cessation of treatment are
- An open study in adults found that one to two six week courses of
cyclosporine resulted in long term remission of atopic eczema at one
year 4 but open trials in children found that continuous rather than
intermittent usage achieved better control 5.
- The starting dose is usually 5mg/kg daily in divided doses tapering
down to 2-3mg/kg daily in divided doses6.
- Careful monitoring is essential with cyclosporine use. Documented
side effects include nephrotoxicity, immunosuppression, and predisposition
to cancer, particularly cutaneous non-melanoma skin cancer and lymphoma
1. Cyclosporine also interacts with a variety of commonly used blood
pressure medications, statins, antibiotics, antifungals, antiepileptics,
and HIV protease inhibitors 1,8,9.
- Hanifin J M, Cooper K D ,Ho VC et al. Guidelines of care for atopic
developed in accordance with the AAD. J Am Acad Dermatol 2004;50:391-404.
- Naeyaert JM , Lachapelle JM, Degreef H et al Cyclosporine in atopic
of the literature and outline of a Belgian consensus. Dermatology 1999;198:142-52
- Granlund H, Erkko P, Sinasalo M. Cyclosporin in atopic dermatitis:
time to relapse and
effect of intermittent therapy. Br J Dermatol 1995;132:106-12
- Grandlund H, Erkko P, Reitamo S . Long term follow up of eczema
with cyclosporine. Acta Derm Venereol 1998;78(1);40-3
- Harper JI, Ahmed I, Barclay G et al . Cyclosporin for severe childhood
dermatitis. Short course versus continuous therapy. Br J Dermatol 2000;142:52-8
- Sowden JM , Berth-Jones J, Ross JS et al. Double-blind, controlled,
of cyclosporine in adults with severe refractory atopic dermatitis.
- Leung DY, Bieber T. Atopic dermatitis. Lancet 2003:361;151-60
- Thompson PD ,Clarkson P, Karas RH . Statin associated myopathy.
J Am Med Ass
- Akhavan A , Rudikoff D . The treatment of atopic dermatitis with
immunosuppressive agents. Clinics Dermatol 2003;21:225-40
- Sauder D N . Mechanism of action and emerging role of immune response
therapy in dermatological conditions. J Cutan Med Surg 2005;3-12
Azathioprine [ 2+ ; B ]
- Often used after cyclosporine in treating moderate to severe atopic
- Very little scientific data except for two recent randomized controlled
trials 1,2 . The results of a crossover trial using 2.5 mg/kg azathioprine
showed a 25% improvement in disease activity , but 35% of the participants
withdrew owing to side effects. Using a parallel group design and using
doses of azathioprine according to thiopurinemethyl transferase ( TPMT
) , a key enzyme in thiopurine metabolism status , Meggitt et al observed
a larger mean improvement in disease activity (37%) and a lower dropout
rate of 15% .Sustained improvement for at least three months after stopping
azathioprine may also occur 2 . In a retrospective open study , Murphy
et al found that azathioprine resulted in a good or excellent response
( 85% ) children with atopic eczema 3.
- Treatment with azathioprine as systemic monotherapy is a cost effective
adjunctive treatment in moderate to severe atopic eczema that does not
respond despite optimum therapy with topical corticosteroids 4, 5. Optimal
use is achieved when combined with systemic steroids, providing a steroid
- Dose: 2.5mg per kilogram per day. Can start with 50mg a day increasing
it gradually. Onset of effect is slow and therapeutic effects are not
dramatic which is discouraging to patients.
- In the randomized controlled trials no participants developed serious
laboratory abnormalities, although hypersensitivity reactions occurred
in two patients 2. Long term risks are unknown 6.
- Berth-Jones J, Takwale A, Tan E et al . Azathioprine in severe adult
atopic eczema; a double blind , placebo controlled ,crossover trial
. Br J Dermatol 2002; 147;324-30
- Meggitt S J, Gray JC , Reynolds NJ . Azathioprine dosed by thiopurine
methyltransferase activity for moderate to severe atopic eczema: a double
–blind , randomized controlled trial . Lancet 2006;367 : 839-46
- Murphy LA , Atherton D . A retrospective evaluation of azathioprine
severe childhood atopic eczema using TPMT levels to exclude patients
at high risk of myelosuppression. Br J Dermatol 2002;147: 308-15.
- Get lancet reference
- Buckley D A , Baldwin P, Rogers S. The use of azathioprine in severe
adult atopic eczema. J Eur Acad Dermatol Venereol 1998;11:137-140
- Kwon JH, Farrel RJ . The risk of lymphoma in the treatment of inflammatory
bowel disease with immunosuppressive agents. Crit Rev Clin Oncol 2005;56:169-78.
- Meggit SJ , Reynolds NJ . Azathioprine for atopic dermatitis. Clin
Exp Dermatol 2001;26:369-75
Methotrexate [ 0 ]
- Methotrexate is a folic acid antagonist that prevents the production
of tetrahydrofolic acid by binding to dyhydrofolate reductase .
- Methotrexate probably causes a shift from TH1 to TH2 responses by
both suppressing the stimulating the production of natural cytokine
inhibitors such as IL-1 receptor antagonists 1.
- There are no evidence based RCTs to support its use in AD. 2,3.
- Rothe MJ, grin-Jorgensen C, Ramsey WH ,et al : Monitoring patients
taking methotrexate J Am Acad Dermatol 1995;32: 680
- Egan CA, Rallis TM , Meadows KP. Low dose oral methotrexate treatment
for recalcitrant palmoplantar pompholyx. J Am Acad Dermatol 1999;40:612-4
- Shaffrali FC, Colver GB , Messenger AG. Experience with low dose
methotrexate for the treatment of eczema in the elderly J Am Acad Dermatol
Mycophenolate mofetil (MMF) [ 3;D ]
- Recently re-introduced to the dermatological world 6. The literature
based uses range from various inflammatory to autoimmune disorders6.
However only anecdotal case reports are found in the literature and
larger studies are therefore required.
- The standard dosage in adults for most dermatological conditions
appears to be 1 gram per os BD. It is available as a 250mg (cellcept)
capsule and its absorption is enhanced on an empty stomach.
- Severe refractory atopic dermatitis was documented to be responsive
to MMF in two patients1. A larger trial of ten patients treated with
MMF ( 2g/d ) demonstrated improvement in their atopic dermatitis severity
scores as measured by SCORAD indices, and without major side effects2.
These two open trials using 2.0g MMF daily reported improvement in disease
( 68% median reduction and 55% mean reduction ) 1,2 .whereas a third
study using 2.0 to 2.5 g daily reported no clinically relevant effect
in five patients.
A recent retrospective study on 20 patients showed MMF to be effective
and well tolerated . 17 patients improved within 4 weeks . 10 patients
had disease remission and 7 patients attained satisfactory control of
their atopic dermatitis using MMF as maintenance therapy3. The success
of this study was limited by there being no control group and the lack
of a standardized scoring index to assess improvement. Also the concomitant
use of adjuvant therapies made the contribution of MMF alone difficult
- The safety profile in long term usage of MMF also needs to be evaluated.
The current concerns with MMF therapy are the induction of neutropenia
in the development of lymphomas and other malignancies7,8.
- Neuber K , Schwartz I, Itschert G. Treatment of atopic eczema with
oral mycophenolate mofetil. Br J Dermatol 2000;143:385-91
- Grundmann-Kollman M, Podda M , Ochsendorf F. Mycophenolate mofetil
is effective in the treatment of atopic dermatitis. Arch Dermatol 2001;137:870-3
- Murray M L and Cohen JB . Mycophenolate mofetil therapy for moderate
atopic dermatitis. Clinical Exp Dermatol 2006;2:1-5
- Jones EL , Epinette WW , Hackney VC et al . Treatment of psoriasis
mycophenolic acid . J Invest Dermatol 1975;65:537-42
- Alsberg CL, Black OF . Contribution to the study of maize deterioration
. US Dept
Agr Plant Industry Bull 1913;270:7-48
- Liu V and Mackool BT . Mycophenolate in Dermatology. Jnl Dermatological
Treatment 2003;14:203 - 210
- Stern DK , Tripp JM , Ho VC , Lebwohl M. Use of systemic immune
dermatology : an update . Dermatol Clin 2005;23:259-300
- Heymann WR . Mycophenolate mofetil J Am Acad Dermatol 2005;53:1045-6
This group of drugs are often needed to treat complicating bacterial infections,
especially those caused by Staphylococcus aureus. This can also help to
control difficult to manage dermatitis per se. It is, however not advisable
to use long-term antibiotics to suppress growth of this organism as the
disadvantages outweigh the benefits.
Anti-herpes drugs like acyclovir, valacyclovir and famciclovir are sometimes
needed to treat complicating Herpes simplex infections.