ABSTRACT

Several variants of psoriasis are seen in children, the most prevalent types include plaque, guttate, and psoriatic diaper rash; pustular and erythrodermic psoriasis are less frequently observed. Genetic susceptibility and environmental triggers are both involved in the development of this autoimmune disease. As well as improving symptoms, a treatment plan should strive to identify and eliminate precipitating factors. Topical medications are the first choice therapy for children with psoriasis. Systemic agents are used to treat more severe cases. Patient education and supportive care should be incorporated into the treatment plan.

Key Words:
adolescent, children, psoriasis

Introduction

Psoriasis is a common condition that affects about 3.5% of the population.¹ In greater than 33% of patients, the initial presentation of psoriasis occurs within the first two decades of life.^2-5 It is estimated that 10% of patients develop psoriasis before the age of 10.⁶ In a review of 1262 cases of psoriasis, initial disease onset occurring before the age of 2 years was found in 14-27%.⁷ Children present with the same clinical variants of psoriasis seen in adults, though they may differ in distribution, morphology, and natural history.⁵

Etiology

Psoriasis is a T-cell mediated chronic inflammatory condition characterized by keratinocyte hyperproliferation, vascular endothelial proliferation, and inflammatory cell infiltration.^8,9 The exact cause and pathogenesis of psoriasis are not well understood, but are known to be multifactorial, having both genetic and environmental influences.⁹ Seventy-one percent of children with psoriasis have a positive history for psoriasis in a first degree relative.⁷ The PSORS1 gene has been shown to be a major genetic determinant of Type 1 early onset non-pustular psoriasis.^5,10 HLA-Cw6 is the major disease allele at the PSORS1 locus that confers susceptibility to early onset disease.^2,5,11,12

Exogenous and endogenous factors, such as upper respiratory infection, emotional stress, skin injury, and drugs, can precipitate and exacerbate psoriasis in children.^2,6,8,13 Streptococcal pharyngitis and perianal streptococcal dermatitis are common causes of guttate psoriasis in children.^2,7,8 Frequency of sore throat and skin trauma leading to an exacerbation of psoriasis is greater in pediatric onset psoriasis than adult onset.^5,13 The appearance of new lesions in times of emotional stress is also more common in pediatric patients.¹³ Injury or irritation of normal skin can induce new psoriatic lesions at the site, known as the Koebner phenomenon. Antimalarials and the withdrawal of corticosteroids play a significant role in rebound psoriasis and the induction of childhood psoriasis, whereas β-blocking agents and lithium are recognized triggers for psoriasis in adult patients.^11,14

Presentation

Classic psoriasis presents as sharply demarcated, deep red plaques with silvery scales.⁹ The presentation in children may be atypical, thus making a diagnosis difficult in such cases; however, there are a few clinical features that can aid in identification. The Auspitz sign, which is pinpoint bleeding upon removal of scales, is characteristic of psoriasis.^2,15 Nail changes, such as oil spots, onycholysis, subungual hyperkeratosis and pitting (the most common finding), are frequently observed in adolescents with psoriasis and are valuable clues in establishing diagnosis.^2,8,9,16,17

Psoriasis often presents differently in children than in adults. Involvement of the face and flexural regions are more common in children than adults, and psoriatic lesions in the diaper area are prevalent during infancy.⁸ Plaque-type psoriasis is the most common variant in both adults and children, however, lesions in children are smaller, thinner, and less scaly than those seen in adults.^2,5,7 Pustular and erythrodermic psoriasis are less frequently seen in pediatric than adult patients. Though rare in occurrence, there are also reports of congenital^6,18 and naevoid¹⁹ forms of psoriasis.

Plaque-type psoriasis is the most prevalent variant that affects children. Plaque psoriasis routinely affects the scalp. Scalp involvement characterized by pityriasis amiantacea (thick, adherent white scales that encase the hair shaft) may lead to temporary hair loss and visible psoriatic alopecia.^2,8 Plaque psoriasis can also affect the face, as well as extensor and flexor surfaces of the knees and elbows.^2,9

Psoriatic diaper rash is the next most common variant, with highest prevalence in children under the age of 2 years.^5,7 Psoriatic diaper rash features a bright red, well-demarcated, glazed, diaper rash that may be followed by widespread dissemination of small psoriasis-like lesions.² This clinical variant can be differentiated from irritant diaper dermatitis by its unique presentation and poor response to conventional treatment for diaper dermatitis.²

Guttate type psoriasis presents as annular, localized, red to salmon colored plaques with hyperkeratosis, commonly located on the trunk, abdomen, and back.⁸ Streptococcal pharyngitis and perianal dermatitis frequently precede abrupt appearances of guttate psoriasis.²⁰ Acute guttate psoriasis that is preceded by an upper respiratory infection may resolve spontaneously after 3-4 months; however, a significant portion of patients eventually develop chronic plaque disease.^2,9

Pustular and erythrodermic psoriasis are less frequently seen in children than adults.^2,9 Pustular psoriasis is distinguished by the presence of sterile pustules on erythematous skin; the pustules may be either localized or generalized.² Generalized pustular psoriasis in children has a more benign course than in adults.²¹ Annular pustular psoriasis, a manifestation of generalized pustular psoriasis, occurs more frequently in children than in adults.^2,22 It is characterized by annular lesions with erythematous, scaly, and pustular margins. Erythrodermic psoriasis presents as erythema on >90% of the body surface area with less scales than plaque psoriasis.²¹

Treatment

When treating children with psoriasis, it is important to educate both patients and parents about the nature of the disease. It must be made clear that psoriasis is a chronic skin disorder without a permanent cure and, therefore, the goal of treatment is to establish disease control and prolong periods between flares.²³ Treatment results may vary from flattened plaques and reduced visibility of lesions (e.g., less redness and scale) to complete remission.² Proper education about the disease and treatment options often enhances the compliance of patients and their parents.^2,9

The patient’s age, quality of life factors, Psoriasis Area and Severity Index (PASI) score, and therapeutic preferences should all be considered when determining treatment selection.^5,8 The majority of children have mild disease that can be successfully treated with topical agents. Systemic drug therapy in children is generally reserved for severe disease that is resistant to other treatments.⁵ A prevention strategy should aim to control and reduce known exogenous and endogenous factors that trigger or contribute to disease exacerbation, like skin trauma, emotional stress, aggravating drugs, and upper respiratory infections.¹³

A chronic, visible condition like psoriasis can have a significant impact on children’s psychosocial development.²⁴ Through school years and adolescence, children may require substantial family and professional support to cope with the psychological and social sequelae of psoriasis, particularly the negative reactions of other children.²⁵

Topical Medications

Corticosteroids

Corticosteroids have anti-inflammatory and antiproliferative properties that reduce erythema, scaling, and pruritus.^5,9 Corticosteroids have high acceptability among patients because they do not stain and are almost odorless. This acceptance combined with wide availability, ease of use, and faster onset of action make corticosteroids the first choice treatment of childhood psoriasis, especially in flexural disease.² Very high potency corticosteroids should be used only sparingly in combination or rotation with steroid sparing alternatives, such as coal tar, liquor carbonis detergens, anthralin, calcipotriene (calcipotriol), and topical calcineurin inhibitors.⁵ Combination therapy can help reduce side-effects caused by topical steroids without reducing the efficacy of the treatment.⁹ Side-effects of topical steroids include skin atrophy, striae, telangiectasia, acneiform eruptions, and in rare cases, suppression of the hypothalamic-pituitaryadrenal axis may occur after prolonged widespread application or overuse, especially of potent preparations.^2,5 There are reports of tachyphylaxis associated with prolonged corticosteroid use in the treatment of psoriasis. However, some attribute this phenomenon to decreased adherence to long-term therapeutic regimens.^5,26,27 Treatment with corticosteroids should be gradually withdrawn to prevent rebound flares.⁹

Coal Tar

The use of coal tar, which is both antiproliferative and antipruritic, is limited by its strong odor and ability to stain. A modified coal tar preparation, liquor carbonis detergens (LCD), has largely replaced crude coal tar in outpatient settings because of its superior cosmetic acceptability.⁵ Coal tar is less irritating than calcipotriene and anthralin on the face and flexures, sites commonly affected in children.²⁵

Anthralin

Anthralin (dithranol) is a potent anti-inflammatory and antiproliferative agent. Its negligible systemic absorption makes it a safe and easy treatment option for children.⁵ Anthralin’s use is limited due to its tendency to stain skin and clothing and irritate healthy skin. It is not recommended for application on the face, flexures and genitalia, and should not be used in erythrodermic or pustular psoriasis.⁹ In an open study of 58 children ages 5-10 years, remission was achieved in 47 patients (81%) using dithranol at concentrations up to 1%.²⁸

Calcipotriene

Calcipotriene (calcipotriol) is a vitamin D analogue that stimulates keratinocyte differentiation and inhibits DNA synthesis and proliferation.²³ It is considered to be a successful and safe treatment for children with mild to moderate plaque psoriasis involving <30% of the body surface.² Calcipotriene is non-staining and odorless.⁹ Potential side-effects include local intolerance or irritation.⁸

Topical Calcineurin Inhibitors

Tacrolimus and pimecrolimus are non-steroidal immunomodulating macrolactams that inhibit the production and release of interleukin-2 (IL-2) and subsequent T-cell activation and proliferation, through blockade of the enzyme calcineurin.⁵ They are particularly useful for treating pediatric psoriasis in areas where atrophy is a risk, such as the face, intertriginous regions, and the groin.⁹

Salicylic Acid

Salicylic acid is recommended for use on thick localized plaques.^2,5 However, salicylic acid should be avoided in infants and children less than 6 years of age, or otherwise used with caution, as there is a risk of percutaneous absorption and salicylate intoxication.^2,5

Phototherapy

Phototherapy is extensively used in adults and is a treatment option for children with widespread plaques.² Narrowband UVB (NB-UVB) phototherapy may be combined with topical therapies to enhance efficacy of both modalities and to reduce the NB-UVB dose and carcinogenic risk.^2,5 Psoralen + UVA (PUVA) therapy is not generally recommended in young children, but may be used in adolescents with caution.^5,9,25 When PUVA is administered, topical psoralens are chosen preferentially over oral psoralens to avoid gastrointestinal side-effects and the necessity to wear protective eye gear for 24 hours.^2,8 NB-UVB is considered the first-line phototherapy because it is as effective as PUVA, more convenient, and less carcinogenic.^5,29

Systemic Medications

Acitretin

Acitretin, a retinoid, is an effective treatment for severe plaque, pustular, and erythrodermic psoriasis in adolescents.⁵ It can be used as monotherapy or in combination with topical agents and NB-UVB phototherapy. Side-effects include cheilitis, pruritus, and hair loss.² Because of its high teratogenic risk, acitretin should be used with caution in girls of childbearing age and must be accompanied by oral contraceptive therapy, as well as counseling, to avoid pregnancy during and 3 years after the completion of treatment.³⁰ Long-term use can lead to premature epiphyseal closure and radiologic bone evaluations may be required.³⁰

Methotrexate

Methotrexate, a folic acid antagonist, is rarely used in children and reserved for severe psoriasis unresponsive to other treatments.^30,31 Side-effects include nausea, headache and gastrointestinal upset, which can be minimized with folic acid supplements.⁹ Regular screening of the patient’s blood count, liver enzymes, and renal function is necessary to monitor for potential development of acute hematotoxicity and hepatotoxicity.^2,9

Cyclosporine

Cyclosporine is an immunosuppressant that can be used to treat extremely severe cases of pediatric psoriasis. The initial dose of cyclosporine is 3 mg to 5 mg/kg per day and should be gradually tapered to the lowest dose that can maintain disease control.^2,5 Major risks of hypertension and renal dysfunction necessitate close monitoring.

Biologics

Biologics are a class of drugs that include antibodies and fusion proteins targeting cytokines. Etanercept and infliximab are tumor necrosis factor-alpha inhibitors that are used for the treatment of pediatric autoimmune diseases. Etanercept is an effective method of treatment for moderate to severe plaque-type childhood psoriasis.^31,32 In a double-blind trial designed to assess the efficacy and safety of etanercept in children with plaque-type psoriasis, both non-infectious and infectious adverse effects from treatment were observed, the most serious of which were gastroenteritis and pneumonia.³² All adverse affects were resolved without sequelae.³²

Antibiotics and Tonsillectomy

Pharyngeal and perianal streptococcal infections may precipitate or exacerbate acute guttate and pustular psoriasis.²⁰ Antibiotics may be prescribed to treat patients with recurrence or flare of guttate psoriasis, and tonsillectomy may be considered for refractory psoriasis and recurrent tonsillitis.³⁰ However, these treatments are controversial, as there is a lack of controlled studies to support their efficacy.

Conclusion

Psoriasis is a life-long disease that often begins during childhood. In order to correctly diagnose and treat children and adolescents, it is important to recognize the different presentations of the disease in this cohort. Children with psoriasis, including their parents and caregivers, should be educated about the natural history and exogenous and endogenous factors responsible for increased disease morbidity, as well as receive support and counseling to help cope with their condition.

References

1. Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol 2009 Feb;60(2):218-24.
2. Benoit S, Hamm H. Childhood psoriasis. Clin Dermatol 2007 Nov-Dec; 25(6):555-62.
3. Romiti R, Maragno L, Arnone M, et al. [Psoriasis in childhood and adolescence]. An Bras Dermatol 2009 Jan-Feb;84(1):9-20.
4. Rogers M. Childhood psoriasis. Curr Opin Pediatr 2002 Aug;14(4):404-9.
5. Cordoro KM. Management of childhood psoriasis. Adv Dermatol 2008; 24:125-69.
6. Farber EM, Jacobs AH. Infantile psoriasis. Am J Dis Child 1977 Nov; 131(11):1266-9.
7. Morris A, Rogers M, Fischer G, et al. Childhood psoriasis: a clinical review of 1262 cases. Pediatr Dermatol 2001 May-Jun;18(3):188-98.
8. Silverberg NB. Pediatric psoriasis: an update. Ther Clin Risk Manag 2009; 5:849-56.
9. Leman J, Burden D. Psoriasis in children: a guide to its diagnosis and management. Paediatr Drugs 2001;3(9):673-80.
10. Henseler T, Christophers E. Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. J Am Acad Dermatol 1985 Sep;13(3):450-6.
11. Nair RP, Stuart PE, Nistor I, et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet 2006 May;78(5):827-51.
12. Valdimarsson H. The genetic basis of psoriasis. Clin Dermatol 2007 Nov-Dec;25(6):563-7.
13. Raychaudhuri SP, Gross J. A comparative study of pediatric onset psoriasis with adult onset psoriasis. Pediatr Dermatol 2000 May-Jun;17(3):174-8.
14. O’Brien M, Koo J. The mechanism of lithium and beta-blocking agents in inducing and exacerbating psoriasis. J Drugs Dermatol 2006 May;5(5):426-32.
15. Bernhard JD. Clinical pearl: Auspitz sign in psoriasis scale. J Am Acad Dermatol 1997 Apr;36(4):621.
16. Al-Mutairi N, Manchanda Y, Nour-Eldin O. Nail changes in childhood psoriasis: a study from Kuwait. Pediatr Dermatol 2007 Jan-Feb;24(1):7-10.
17. Kumar B, Jain R, Sandhu K, et al. Epidemiology of childhood psoriasis: a study of 419 patients from northern India. Int J Dermatol 2004 Sep;43(9):654-8.
18. Lerner MR, Lerner AB. Congenital psoriasis: report of three cases. Arch Dermatol 1972 Apr;105(4):598-601.
19. Atherton DJ, Kahana M, Russell-Jones R. Naevoid psoriasis. Br J Dermatol 1989 Jun;120(6):837-41.
20. Honig PJ. Guttate psoriasis associated with perianal streptococcal disease. J Pediatr 1988 Dec;113(6):1037-9.
21. Howard R, Tsuchiya A. Adult skin disease in the pediatric patient. Dermatol Clin 1998 Jul;16(3):593-608.
22. Liao PB, Rubinson R, Howard R, et al. Annular pustular psoriasis–most common form of pustular psoriasis in children: report of three cases and review of the literature. Pediatr Dermatol 2002 Jan-Feb;19(1):19-25.
23. Kragballe K, Wildfang IL. Calcipotriol (MC 903), a novel vitamin D3 analogue stimulates terminal differentiation and inhibits proliferation of cultured human keratinocytes. Arch Dermatol Res 1990;282(3):164-7.
24. Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br J Dermatol 2006 Jul;155(1):145-51.
25. Burden AD. Management of psoriasis in childhood. Clin Exp Dermatol 1999 Sep;24(5):341-5.
26. Zivkovich AH, Feldman SR. Are ointments better than other vehicles for corticosteroid treatment of psoriasis? J Drugs Dermatol 2009 Jun;8(6):570-2.
27. Feldman SR. Tachyphylaxis to topical corticosteroids: the more you use them, the less they work? Clin Dermatol 2006 May-Jun;24(3):229-30.
28. Zvulunov A, Anisfeld A, Metzker A. Efficacy of short-contact therapy with dithranol in childhood psoriasis. Int J Dermatol 1994 Nov;33(11):808-10.
29. Van Weelden H, Baart de la Faille H, Young E, et al. Comparison of narrowband UV-B phototherapy and PUVA photochemotherapy in the treatment of psoriasis. Acta Derm Venereol 1990;70(3):212-5.
30. Cordoro KM. Systemic and light therapies for the management of childhood psoriasis: part II. Skin Therapy Lett 2008 May;13(4):1-3.
31. de Jager ME, de Jong EM, van de Kerkhof PC, et al. Efficacy and safety of treatments for childhood psoriasis: a systematic literature review. J Am Acad Dermatol 2010 Jun;62(6):1013-30.
32. Paller AS, Siefried EC, Langley RG, et al. Etanercept treatment for children and adolescent with plaque psoriasis. N Engl J Med 2008 Jan 17;358(3):241-51.

¹DermSurgery Associates, Houston, TX, USA
²Department of Dermatology, Weill Cornell Medical College, The Methodist Hospital, Houston, TX, USA
³Department of Dermatology, The University of Texas Medical School at Houston, Houston, TX, USA

ABSTRACT

Pregnancy is characterized by multiple physiologic changes. During the entire gestational period, both mother and infant are vulnerable to a variety of external and internal factors. Maternal disease, use of certain medications, drugs, alcohol, smoking, and radiation exposure can have devastating effects on the fetus. Pregnancy-related complications in women with psoriasis can be caused by both the disease and the treatment. The response of the maternal placenta to psoriasis-induced inflammation and comorbid conditions, such as obesity, hypertension, and depression, may also influence the pregnancy. Herein, we review the relationship between psoriasis and undesirable pregnancy outcomes.

Key Words:
comorbidities, complications, drug therapy, pregnancy, psoriasis, risk factors

Introduction

Pregnancy is a unique physiologic state characterized by an array of significant changes in the endocrine, vascular, and respiratory systems. These changes facilitate fetal growth and development and prepare the woman’s body for labor and delivery. During the first trimester of pregnancy (weeks 0-13), the developing embryo undergoes organogenesis and is especially susceptible to injury from systemic maternal diseases, medications, drugs, alcohol, and smoking. During this period many pregnant women are often unaware that they are even pregnant, and therefore do not actively minimize risks to the fetus.¹ This may include women with chronic diseases, such as those with moderate to severe psoriasis, who require multiple drugs for treatment.

Psoriasis is an autoimmune inflammatory skin disease with manifestations resulting from a complex interplay between genetics and the environment. The incidence of psoriasis is bimodal, with one peak between the ages of 15-30 years and a second between 50-60 years.^2,3 The average age of diagnosis in women is 28, a prime age for pregnancy.^3,4 Annually, there are approximately 65,000-107,000 births to women with psoriasis, of whom 9,000-15,000 have moderate to severe disease.²

Psoriasis lesions are well-circumscribed, erythematous plaques with a fine silvery scale; they predominate on the scalp and extensor surfaces, yet can occur anywhere on the body; there may also be nail changes. The severity of the condition is determined by two major criteria: 1) the extent of body surface area (BSA) involved and 2) the location of the lesions (for example, if psoriatic plaques are present on the palms and soles, it is considered severe, regardless of percentage of BSA involvement). In general, mild psoriasis occurs when lesions are limited to < 3% BSA, moderate psoriasis with 3-10% BSA, and severe psoriasis with >10% BSA. Quality of life issues for the patient also determine severity. While mild psoriasis can typically be controlled with topical treatments, moderate to severe psoriasis may require systemic therapy.

The management of psoriasis in pregnant women is challenging, since the physician and patient must balance teratogenic risks associated with certain drug therapies to potential adverse pregnancy outcomes from uncontrolled skin inflammation and excess cytokines inherent with the disease process. There is very little data detailing the effects of psoriasis on pregnancy outcomes.^2,4-6 Herein, we explore potential direct and indirect effects of psoriasis on pregnancy and the effects of pregnancy on psoriasis.

Direct Effects of Psoriasis on Pregnancy

In general, inflammatory/autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and psoriasis have been shown to be associated with low birth weight (LBW), preterm birth, and abortions.^5,7 Autoimmune inflammation in psoriasis results from dysfunctional T helper cells with a concomitant amplification of pro-inflammatory cytokines (most notably TNF-alpha, IL1 and IL6). Excess cytokines yield endothelial dysfunction with resulting systemic and placental vasculopathy through induction of platelet aggregation, intermittent vasospasm, and activation of the clotting system.^5,8 Placental vasculopathy has been postulated to contribute to LBW infants.⁵ LBW is also a complication of preeclampsia, which is similarly associated with an activated inflammatory state and increased levels of the same cytokines seen in psoriasis (CRP, TNF-alpha and IL6).^8-10 There is conflicting data regarding the correlation between psoriasis during pregnancy and infant birth weight.^5-7 Yang et al studied 1,436 mothers with psoriasis compared to 11,704 mothers without psoriasis, and found that LBW was associated only with severe psoriasis (defined as any mother who had received photochemotherapy or systemic therapy within the 2 years prior to delivery).⁵ In contrast, Cohen-Barak et al analyzed 68 pregnant women, but found that mothers with moderate to severe psoriasis were more likely to give birth to large infants when compared with controls.⁷ This group found psoriasis to be associated with a higher risk for spontaneous and induced abortions, which is also seen in inflammatory conditions including rheumatoid arthritis and systemic lupus erythematosus.⁷

Indirect Effects of Psoriasis on Pregnancy

Comorbidity Induced Adverse Effects

The stress associated with chronic, relapsing diseases may affect mental health, increasing the tendency for alcohol misuse, depression, weight gain, and smoking. Psoriasis is also associated with higher rates of comorbid systemic conditions including diabetes mellitus (DM), cardiovascular disease (atherosclerosis, congestive heart failure, and myocardial infarction), obesity, and metabolic syndrome (consisting of obesity, high blood sugars, high triglyceride levels, low high-density lipoprotein, and hypertension). Obesity and hypertension have been shown to be at least twice as common in patients with psoriasis.^4,11 Pregnant women with psoriasis are more likely to be overweight/obese, depressed, smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements.⁴

Both the comorbid conditions associated with psoriasis and the drugs used to treat them may be harmful to the developing fetus. Hypertension (HTN) is known to be associated with LBW secondary to placental insufficiency, perinatal mortality, and preterm delivery, in addition to increased risk for acute maternal morbidities.¹² The drugs commonly used to treat HTN, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, can be teratogenic.^13,14 DM is associated with increased neonatal mortality and multiple morbidities including, fetal macrosomia, post-natal hypoglycemia, and congenital malformations including transposition of the great vessels.¹⁵ Furthermore, pregnancy has been shown to hasten the progression of DM; healthy women may even develop diabetes only during pregnancy, which is known as gestational DM.¹⁵ Alcohol misuse may result in fetal alcohol syndrome and LBW. Maternal consequences of depression include inadequate weight gain, insufficient utilization of prenatal care, and increased substance abuse, whereas fetal consequences can include premature birth, LBW, decreased Apgar scores, and smaller head circumference.¹⁶ Obesity has been associated with macrosomia, low Apgar scores, and premature birth.⁴ Smoking may increase the risk for oral clefts and reduced birth weight.⁴

Treatment Induced Adverse Effects

Little evidence exists to delineate the effects of psoriatic medications on human pregnancy due to ethical implications associated with investigating potentially teratogenic medications.¹ General guidelines are based on retrospective data and on cases in which a woman may have used a questionable medicine without yet realizing she was pregnant. Mild psoriasis can usually be adequately treated with topical medications, while severe psoriasis may require systemic treatment. Limited amounts of topical preparations including corticosteroids, calcipotriene, coal tar, and anthralin appear to be safe. There is a low likelihood for significant systemic absorption with these topical preparations if used in conservative application patterns.^1,5 The risk for potential teratogenicity increases in a dose-dependant manner as systemic absorption increases. The factors that increase systemic absorption include prolonged duration of treatment, large amounts of medication applied, a compromised epidermal barrier, and occlusion.¹

Systemic medications used for psoriasis unresponsive to topical therapies include acitretin, methotrexate, mycophenolate mofetil, and biologics such as adalimumab, alefacept, etanercept, infliximab, and ustekinumab. Most of the systemic antipsoriatic therapies are associated with significant toxic effects to the fetus and should be avoided during pregnancy. Acitretin (an oral retinoid) is strictly prohibited before or during pregnancy since it can cause a classic retinoid syndrome, consisting of well-characterized craniofacial, cardiac, thymic, and CNS malformations.¹ Furthermore, acitretin can linger for over 2 months after the last dose, so patients should stop this drug months before attempting to conceive.¹ Methotrexate is an antimetabolite that is associated with a specific constellation of prenatal growth deformities, including growth retardation, large fontanelles, craniosynostosis, ocular hypertelorism, micrognathia, limb abnormalities, and developmental delay; these effects are dose-related. Mycophenolate mofetil interferes with DNA and RNA synthesis, and case reports indicate that it can cause microtia or anotia, cleft lip/palate and heart defects. Systemic corticosteroids are not commonly used for psoriasis; however, they remain the best available treatment for a rare condition, known as impetigo herpetiformis, a form of pustular psoriasis seen in pregnancy.¹⁷ The side-effects of systemic steroids have mostly been studied in pregnant patients with asthma and they include orofacial clefts, intrauterine growth restriction, and suppression of the hypothalamic-pituitary axis.¹ There is very limited data with regard to the biologics, but infliximab has been associated with congenital malformations in two infants and death in a third due to uncontrollable intracranial and pulmonary bleeding.^1,18

Phototherapy with broad-band (290-320 nm) ultraviolet B (UVB) and narrow-band UVB (311-312 nm) appear to be safe during pregnancy.¹ The safety of systemic PUVA with psoralens is unknown, although mutagenic potential has been shown in rat studies; however, topical PUVA limited to small areas might be safe. Cyclosporin A in pregnant organ transplant recipients have failed to show an increased risk to the fetus1 and may therefore be an option in pregnant psoriatic patients.

Effects of Pregnancy on Psoriasis

Pregnancy may influence the severity of psoriasis.^6,19 In fact, psoriasis often improves during pregnancy. Boyd et al reported on a study of 90 women with psoriasis, who responded to a questionnaire regarding the condition of their psoriasis during pregnancy.⁶ Seventy-seven percent of these women noticed a change in their psoriasis, the majority of whom (63%) experienced improvement; within 4 months of giving birth, however, 88% of the women subsequently developed a “post-partum flare” of their psoriasis. Similarly, Murase et al found that 55% of women noted improvement in their psoriasis during pregnancy and 65% experienced worsening of their psoriasis post-partum.¹⁹ The patients with greater than 10% BSA who reported improvement during pregnancy noted that lesions decreased on average by 84%.19 Furthermore, the authors found that estrogen, but not progesterone, was associated with changes in psoriasis; they attributed the improvement in psoriasis to the high ratio of estrogen to progesterone.¹⁹ The authors hypothesized that the alterations in immunity (the immune response shifts from TH1 to TH2 dominance) due to hormonal changes in pregnancy, leads to the improvement in psoriasis, as previously shown in other TH1 mediated autoimmune diseases (i.e., rheumatoid arthritis and multiple sclerosis).¹⁹ While the exact mechanism is still not understood, it appears that psoriasis is more likely to improve than worsen during pregnancy with a post-partum flare.

Conclusion

The extent of the potential effects that psoriasis can have on pregnancy is variable. When possible, pregnant women should modify their behaviors and treatments to decrease any risk to themselves and their unborn children. Registries such as the International Psoriasis Council – project on pregnancy and psoriasis2 and the OTIS Autoimmune Diseases in Pregnancy Project4 are in the process of compiling more extensive data for this population. As data from these registries becomes more readily available, we will better understand the true implications of pregnancy on psoriasis and of psoriasis on pregnancy. Treatment plans can subsequently be developed that balance the risks from therapy versus the harmful effects of psoriasis and its associated comorbidities.

References

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8. Guven MA, Coskun A, Ertas IE, et al. Association of maternal serum CRP, IL-6, TNF-alpha, homocysteine, folic acid and vitamin B12 levels with the severity of preeclampsia and fetal birth weight. Hypertens Pregnancy 28(2):190-200 (2009 May).
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15. Tieu J, Middleton P, Crowther CA. Preconception care for diabetic women for improving maternal and infant health. Cochrane Database Syst Rev (12):CD007776 (2010).
16. Marcus SM. Depression during pregnancy: rates, risks and consequences– Motherisk Update 2008. Can J Clin Pharmacol 16(1):e15-22 (2009 Winter).
17. Oumeish OY, Parish JL. Impetigo herpetiformis. Clin Dermatol 24(2):101-4 (2006 Mar-Apr).
18. Srinivasan R. Infliximab treatment and pregnancy outcome in active Crohn’s disease. Am J Gastroenterol 96(7):2274-5 (2001 Jul).
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^1. Weill Cornell Medical College, Methodist Hospital, Houston, TX, USA
^2. DermSurgery Associates, Houston, TX, USA
^3. Department of Dermatology, The University of Texas Medical School at Houston, Houston, TX USA

ABSTRACT

Alcohol is a serious cause of morbidity and mortality in our society and is implicated in multiple health conditions, including hepatic failure, neurological damage, hematological disorders, and nutritional deficiencies, to name a few. Although alcohol induced cutaneous abnormalities can also cause significant morbidity, they tend to be overshadowed by the other disease states associated with alcohol use. In addition to the cutaneous stigmata linked to chronic alcoholic liver disease, alcohol can directly cause or exacerbate several skin conditions. In particular, alcohol misuse is implicated in the development of psoriasis and discoid eczema, as well as confers increased susceptibility to skin and systemic infections. Alcohol misuse might also exacerbate rosacea, porphyria cutanea tarda, and post adolescent acne. Herein, we review the evidence concerning the influences of alcohol in skin conditions with a focus on psoriasis.

Key Words:
alcohol drinking, psoriasis, risk factors, skin disorders

Physiology of Alcohol Induced Toxicity

Alcohol induces a wide range of physiological derangements in the human body. Alcohol is cytotoxic to the liver, leading to alcoholic steatosis, hepatitis and, at later stages, cirrhosis1 with systemic sequelae. Alcohol is also toxic to the bone marrow, particularly the T cells, which in turn leads to attenuated immune function.^2-4 The cardiovascular system may also be adversely affected by excess alcohol use. Specifically, high output cardiac failure, hypertension, and peripheral vasodilatation may be consequences of chronic and acute alcohol intake.^2,5 Finally, alcohol misuse results in a myriad of nutritional deficiencies, including vitamin and trace element deficiencies^2,5 secondary to interference with proper intestinal absorption and poor nutrition. All of these physiological conditions can contribute to the development of cutaneous manifestations associated with alcohol consumption.

Skin Changes Indirectly Caused by Alcohol

The majority of cutaneous manifestations associated with excess alcohol use are indirectly mediated through the impairment of various organ systems.

Hepatic dysfunction impairs estrogen and bile salt metabolism, resulting in characteristic findings of spider angiomata, palmar erythema, and pruritis.^2,3,5 Male alcoholics are consequently hyperestrogenic.² In addition to high estrogen levels, testosterone production is also inhibited, further exacerbating the problem. Direct inhibition of testosterone production leads to gynecomastia, which presents as a disappearance and redistribution of body and pubic hair and female pattern fat redistribution.² Caput medusae and hemorrhoids are the result of hepatofugal blood flow caused by portal hypertension from liver cirrhosis.

Systemic and superficial skin infections, including bacterial and fungal infections, represent another health problem found to be more prevalent in alcoholics.^2-4 The higher incidence of infections is likely attributable to multiple factors, including alcohol associated nutritional deficiencies in combination with immunodeficiency. Most notably, zinc and vitamin C deficiencies lead to poor wound healing, weakened mucosal barriers, and altered immune defenses with increased risk for infections.

Group A streptococci, Corynebacterium, and Staphylococcus aureus are common bacterial culprits,² as are fungal infections with various tinea and Candida species.^2,3

Malabsorption associated with alcoholism is another mode by which alcohol can produce cutaneous abnormalities. Angular stomatitis, glossitis, perifollicular hemorrhages, pellagra, petechia, and ecchymosis are just a few such cutaneous manifestations.

Skin Changes Directly Caused by Alcohol

Porphyria Cutanea Tarda (PCT) is a metabolic disorder with cutaneous manifestations resulting from an aberration in hepatic heme biosynthesis. Whether acquired or inherited, PCT results from a deficiency in one of the hepatic enzymes involved in porphyrin metabolism, specifically uroporphyrinogen decarboxylase.^2,3,6 The resultant upstream accumulation of photoreactive porphyrin precursors renders the skin extremely photosensitive.² Alcohol is a potent inducer of the hepatic enzymes and the heme metabolic pathway, leading to an accumulation of photoreactive porphyrin compounds proximal to the enzymatic defect and, thus, precipitating PCT flare-ups.^3,6 The cutaneous characteristics of an acute PCT attack include skin blistering and erosions on sun exposed areas^2,3 that resolve leaving residual scarring and milia.

Alcohol impairs the vasomotor center of the brain, inducing peripheral vasodilatation.^2,3 Hence, it has been suggested that this resultant cutaneous vasodilatation may exacerbate rosacea,2,3 contributing to the hallmark redness and flushing. Alcohol can also promote facial erythema in people without rosacea through a genetic deficiency involving an alcohol metabolism enzyme. This phenomenon is most commonly recognized in Asians, as studies have shown that 50% lack the ability to make aldehyde dehydrogenase, leading to an accumulation of acetaldehyde after alcohol consumption.²

The Role of Alcohol in the Pathogenesis of Psoriasis

Psoriasis is a common chronic inflammatory autoimmune condition, affecting approximately 2% of the population in North America.³ It is characterized by epidermal hyperproliferation3,7 and a multifactorial etiology. A complex interplay between genetics and extrinsic factors, including the environment, trauma, infection, and social behaviors appear to be influential on the origin and clinical course of the disease.^3,8-11

Extensive evidence demonstrates a link between excessive alcohol consumption and psoriasis.^3,4,11,12 The amount of alcohol consumed and the type of alcoholic beverage have both been shown to confer the most risk for development and/or exacerbation of plaque psoriasis.¹² A recent prospective study following 82,869 women for 14 years showed that consumption of more then ^2.3 alcoholic beverages per week was a significant risk factor for new onset psoriasis.12 Furthermore, the same study found that consuming non-light beer appears to be an independent risk factor for developing psoriasis in females.¹² Similarly, in males, excess alcohol consumption (at levels higher then 100g/day) appears to be a risk factor for the development and increased activity of psoriasis.^11,13 Moreover, the misuse of alcohol in patients with psoriasis has been shown to be associated with decreased response to treatment.^2,13,14 Interestingly, the cutaneous distribution of psoriasis in heavy drinkers tends to be predominantly acral, involving the dorsum of the hands and digits, resembling that seen in immunocompromised patients, such as those with human immunodeficiency virus (HIV) infection.^2,4 This distribution highlights the potential role of alcohol induced immunosuppression in the development of psoriasis.

The exact molecular mechanisms by which alcohol triggers or exacerbates psoriasis are yet to be fully elucidated. One theory is that alcohol misuse may induce immune dysfunction with resultant relative immunosuppression.^2,3 Alcohol may also enhance the production of inflammatory cytokines and cell cycle activators, such as cyclin D1 and Keratinocyte Growth Factor, which could lead to epidermal hyperproliferation.^2,7,15 Additionally, increased susceptibility to superficial infections commonly observed in alcoholics, such as those caused by Streptococcus and trauma, has also been postulated to have implications in the development of psoriasis.⁷

Although the environment and genetics may not be amenable to prevention or alteration, social behaviors such as alcohol consumption can be modified with appropriate counseling and pharmacological interventions, and therefore, appears to be a promising adjunct to the medical therapy of psoriasis.

Conclusion

An overwhelming amount of evidence suggests a significant link between alcohol and psoriasis – a multifactorial autoimmune disorder. Not only may alcohol contribute, in the presence of appropriate genetic makeup, to the development of psoriasis, it also results in more extensive and treatment resistant disease. Ascertaining carefully the presence of this risk factor in all patients suffering from psoriasis and providing appropriate counseling and education may help the clinician to minimize the risks of disease exacerbation and achieve better therapeutic outcomes.

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