22 September/October 2012 SOUTH AFRICAN RHEUMATOLOGY JOURNAL ARTICLE Psoriasis: an overview Dr WH Fouche Dermatologist in private practice George Introduction The term psoriasis refers to a chronic inflammatory skin disease that commonly presents as well circumscribed erythematous patches covered with silvery scale, although many different clinical subtypes exist. When the scale is removed, small bleeding points appear, the so-called Auspitz sign. It is a specific condition, and although skin lesions are often referred to as psoriasiform, psoriasis is an entity on its own. It is therefore important to confirm a diagnosis of psoriasis, since it will have an effect on the treatment, complications, and long-term prognosis of these patients. Epidemiology It is estimated that psoriasis affects approximately 1-2% of the general population in the western world. It affects both sexes equally, and can occur at all ages, although the mean age of onset is 27 years. Inheritance It is commonly accepted that psoriasis is a genetic disease, and approximately 30% of patients with psoriasis will be able to identify a relative with the disease. The risk of psoriasis for a child with one parent who has the disease is approximately 25%, and when both parents are affected, the risk increases to 60-70%. Incidence will also increase in successive generations. Analysis of the human leukocyte antigen (HLA) haplotypes has provided evidence that the susceptibility to psoriasis is linked to the class 1 and 2 major histocompatibility complex (MHC) on chromosome 6. Early onset psoriasis is mostly associated with HLA-Cw6-B57 and -DR7. Late onset psoriasis is associated with -Cw2. Pustular psoriasis is associated with HLA-B27 whereas -B13 and -B17 expression are increased in guttate and erythrodermic psoriasis. Pathogenesis Certain trigger factors may bring psoriasis to the surface, for example, anxiety and stress, certain medications (Table I), trauma (Koebner phenomenon), and infections with streptococci. Table I. Drug-induced psoriasis Beta blockers Captopril Calcium channel blockers Lipid-lowering drugs Antimalarials (quinine derivatives) Terbinafine Glyburide Lithium Interferon Corticosteroids (may cause rebounds or pustular flares)
24 September/October 2012 SOUTH AFRICAN RHEUMATOLOGY JOURNAL Beta haemolytic streptococci Lancefield group A, C and G can cause exacerbation of chronic plaque psoriasis. Streptococcal pharyngitis also precedes the development of guttate psoriasis. Psoriasis is a hyperproliferative disorder, which is marked by an increase in the growth rate of the keratinocytes and a chronic inflammatory process driven by a complex cascade of inflammatory mediators. T-cells and cytokines are pivotal in the pathogenesis of psoriasis. An over-expression of the type 1 cytokines (pro-inflammatory cytokines) such as (interleukin) IL-2, IL-6, IL-8, IL-12, interferon gamma, and tumour necrosis factor alpha (TNF- ) leads to the accumulation of neutrophils and the development of Th1. There is also a reduction in the expression of the anti-inflammatory cytokines IL- 1RA and IL-10. Transforming growth factor beta (TGF- ) and its receptors are downregulated, leading to abnormal cell proliferation. Circulating natural killer cells are also reduced in patients with psoriasis. The total effect of this is the development of an uncontrolled inflammatory process and an increase in cell proliferation. Clinical features Many different subtypes of psoriasis exist as given in Table II. Table II. Subtypes of psoriasis Plaque psoriasis localised - i.e. scalp psoriasis - limited to a single skin area, e.g. the elbows, knees and the sacrum generalised - psoriasis vulgaris - guttate psoriasis Inverse psoriasis Pustular psoriasis localised - palmoplantar psoriasis - acrodermatitis continua of Hallopeau generalised pustular psoriasis (von Zumbusch) Impetigo herpetiformis Psoriatic arthritis Erythrodermic psoriasis Chronic plaque psoriasis The plaques can start as small erythematous macules that are covered by grey silverish scales. These lesions will continue to increase in size with progressively thickening silvery scales forming on the surface. Most commonly the extensor surfaces of the arms and the legs, the scalp, the sacrum and the umbilical region will be affected, although it can be widespread, covering large areas of the skin. Often there will be involvement of the nails, which can present as pitting of the nails (parakeratosis of the proximal matrix), subungal hyperkeratosis, oil spots or yellowish areas underneath the nail plate (parakeratosis of the distal matrix), or salmon patches, which is the result of nail bed psoriasis. It is also possible that psoriasis can present with only nail involvement without any other skin areas being involved. Guttate psoriasis This type of psoriasis typically affects the younger patient (mostly under the age of 30 years), and presents as an acute eruption of typical psoriasiform lesions, although these lesions are very small with a maximum diameter of approximately 2-5 mm. The eruption is widespread and often follows an infection with one of the streptococcus species, which can present as a streptococcal pharyngitis or a streptococcal pyelonephritis. Inverse psoriasis The term inverse psoriasis refers to psoriatic lesions that develop on the intertrigenous areas, for example the groins, the mammary folds, or the genital areas. They present as an erythematous lesions with well-circumscribed margins appearing in the abovementioned areas, and need to be differentiated from the other causes of intertrigo. Napkin psoriasis is a form of inverse psoriasis that occurs in the diaper area of infants, and should be kept in mind when treating napkin dermatitis. Psoriasis can present with only nail involvement
SOUTH AFRICAN RHEUMATOLOGY JOURNAL September/October 2012 25 Figure 1. Plaque psoriasis Figure 3. Scalp psoriasis Figure 2. Psoriasis of the nails Pustular psoriasis Pustular psoriasis can be generalised, the so-called von Zumbusch psoriasis, or more localised and limited to the palmoplantar regions. Generalised von Zumbusch psoriasis is marked by the formation of pustules, which early in the disease are localised, typically in the palmar and periungal regions and on the margins of existing plaques, but will quickly spread with a generalised eruption. Mucous membranes are often affected. The patient with generalized pustular psoriasis is ill with fever and cachexia and a generalised erythrodermic skin. Burning and itching may also be prominent. Complications include hypoglycaemia, congestive heart failure, pneumonia and hepatitis. Usually a patient who presents with generalised pustular psoriasis will have a history of plaque psoriasis and often-associated psoriatic arthritis. Episodes are often provoked by the withdrawal of systemic corticosteroids. Acitretin is the drug of choice. In the more localised forms of pustular psoriasis, two subtypes can be identified: acrodermatitis continua of Hallopeau and palmoplantar pustulosis. The pustular lesions will be limited to the a cral areas. In acrodermatitis continua, plaques studded with pustules develop on the distal acral areas. Nail bed involvement is usually prominent with the loss of nails (anonychia). Longterm complications include ensuing hyperkeratosis with atrophy of the distal fingertips and functional loss (tapering to long keratotic points). Palmoplantar pustulosis (pustular psoriasis of the extremities) is marked by the formation of pustules on the thenar, hypothenar, and central portions of the palms and soles in a symmetrical fashion. Hyperkeratosis may persist after the pustules have resolved. Usually a patient who presents with generalised pustular psoriasis will have a history of plaque psoriasis
26 September/October 2012 SOUTH AFRICAN RHEUMATOLOGY JOURNAL Psoriatic arthritis Psoriatic arthritis can take on different forms and can be present in approximately 40% of patients with generalised psoriasis. Psoriasis can also present as arthritis without any skin involvement. In 70% of patients, the arthritis will affect a few joints in the fingers and toes in an asymmetrical fashion. Fifteen per cent of patients will have a symmetrical polyarthritis very similar to rheumatoid arthritis, but which is seronegative. A further 5% will have the typical psoriatic arthritis with involvement of the distal interphalangeal joints. Only 5% will develop a destructive arthritis. Figure 4. Guttate psoriasis Impetigo herpetiformis Another form of pustular psoriasis may occur in pregnancy. It starts as flexural erythema with localised pustule formation, spreading to form a typical widespread pustulosis, and the patient becomes increasingly ill. Delivery of the baby is indicated as soon as neonatal lung maturity is established. Many patients respond only to delivery but alternatively systemic steroids should be used. Erythrodermic psoriasis Patients with psoriasis may present with a generalised exfoliative erythroderma, and it can be difficult to distinguish from the other causes of a generalised erythroderma. If no other signs of psoriasis are present, a previous history of psoriasis may help in the diagnosis, but a biopsy is usually necessary to establish a diagnosis. Other causes of generalised erythroderma are seen in Table III. Clinical differential diagnosis of psoriasis Seborrheic dermatitis Chronic eczema, i.e. hand eczema Pityriasis rosea Lichen planus Secondary syphilid Subacute cutaneous lupus erythematosis Dermatomiositis Parapsoriasis Psoriasiform drug reactions Histology of psoriasis Typically one would see acanthosis of the epidermal ridges, which are elongated and club-shaped at the bases, with long oedematous dermal papillae. The suprapapillary plate is thinned and alternating parakeratosis and hyperkeratosis can be seen. In areas of parakeratosis, the granular layer is absent. Large dilated capillaries can be seen in the papillary dermis (responsible for the Auspitz sign). In guttate psoriasis, the epidermal hyperplasia is less prominent. Spongiosis is typically absent, or if observed, scant except in acral lesions where it may be prominent. Accumulation of polymorphs in the parakeratotic stratum corneum, called Munro micro abscesses, is another typical feature. Similar spongiform pustules consisting of neutrophils and a few lymphocytes develop intraepidermally (pustules of Kogoj). In the dermis, a mild perivascular lymphocytic infiltrate can be seen. The features of pustular psoriasis are similar, although the micro abscesses that develop are bigger (macro pustules). All forms of psoriasis are pustular, histologically speaking. Table III. Causes of generalised erythroderma Psoriasis Atopic dermatitis Drug reactions Mycosis fungoides Allergic contact dermatitis Seborrhoeic dermatitis Pityriasis rubra pilaris Paraneoplastic erythroderma
SOUTH AFRICAN RHEUMATOLOGY JOURNAL September/October 2012 27 Treatment Depending on the type and severity of the psoriasis, treatment for every patient should be individualised to suit his/her environment, lifestyle, economical restraints and accessibility to clinics. The best possible result should be achieved with the fewest possible side effects. Figure 5. Pustular psoriasis Figure 6. Napkin psoriasis Figure 7. Psoriatic arthropathy The histological differential diagnosis includes some of the following: Dermatitis Syphilis Certain drug reactions Psoriasiform plaques of Mycosis fungoides A biopsy of an early lesion may show non-specific features and is not diagnostic. Topical treatment Corticosteroids Steroids are probably the most commonly used agent in the treatment of psoriasis. Although it is an important and useful modality, its importance is often overestimated. It is not practical for sustained use over large areas because of the possibility of side effects, which include atrophy of the skin, pyoderma, miliaria, steroid acne, and the possibility of systemic absorption. It can be used intermittently for periods of 2 weeks, and is more effective when used on hydrated skin. When thick keratotic plaques are present, the combination of a steroid with a keratolytic agent like salicylic acid may be useful. Unfortunately, psoriasis tends to rapidly recur when therapy is discontinued. The use of intralesional steroids can be helpful when treating localised plaques resistant to topical applications. Coal tar Although tar preparations have an offensive smell, they can be very useful in the treatment of psoriasis because of their anti-inflammatory properties. Concentrations of 5-10% can be mixed in a variety of preparations and are safe for use over the long term. It is available in shampoo, lotion and cream, and also in liquid form to be used as a bath additive for soaks. Newer preparations are cosmetically and socially more acceptable to patients. They may cause local irritation and can be a photo-sensitiser. Vitamin A preparations The most commonly used vitamin A preparation is Tazarotene. It is receptor specific and plays a part in the modulation of keratinocyte differentiation. Local irritation may occur; therefore combining it with a topical steroid will decrease irritation and increase effectiveness as a combination therapy. Tar preparations have an offensive smell but can be useful
28 September/October 2012 SOUTH AFRICAN RHEUMATOLOGY JOURNAL Vitamin D analogues Vitamin D3 is another substance that is partly responsible for keratinocyte differentiation. Calcipotriene is an analogue of vitamin D that can be used in combination with topical steroids or as a single agent as maintenance therapy. It is safe in long-term therapy and routine monitoring of serum calcium is not necessary. Ultraviolet light Sunlight exposure in moderation will improve psoriasis, but sunburn will cause exacerbation because of the Keener phenomenon. Exposure of the skin to an artificial ultraviolet light source under controlled circumstances is a useful and a cost-effective technique for treating psoriasis. Carcinogenesis with an increased risk of basal cell and squamous cell carcinoma, melanoma and premature photo-ageing is a concern. The risk is dose related, and patients should be carefully selected and monitored, although when proper care is taken, the risk is acceptable. Puva therapy After ingestion of 8-methoxypsoralen at a dose of 0.5 mg/kg two hours before therapy, the skin is exposed to long wave UVA (320-400 nm). To determine length of exposure, the determination of the minimal erythemogenic dose (MED) may be helpful, since the use of skin type is poorly predictive of MED. Erythemogenic doses are more effective than suberythemogenic doses. Exposure will produce a tanning response, and therefore exposure times should be increased as treatment progresses. Usually 20-25 treatments given two to three times per week should be sufficient to clear lesions. Precaution towards sun exposure should be taken during treatment and protective eyewear should be worn. As an alternative to taking oral psoralen, bath PUVA can be considered although it is practically more difficult. The patient is immersed in a psoralen solution before treatment. UVB treatment The use of narrowband UVB has been proven to be more effective than broadband UVB. Wavelengths of between 296 nm and 313 nm are effective, with optimal efficacy at 311 nm. Erythemogenic doses are not required to achieve a response, and treatment is started at 50% of MED, with increases of 10% until maximal dose is reached. Treatments are given two to thress times per week and discontinued upon clearance. Response rates are close to that of PUVA. Alternative techniques are available in the form of the Goeckerman regimen, where topical application of coal tar preparations and daily coal tar baths are combined with UV exposure to obtain clearance. A second technique making use of daily coal tar baths combined with the application of anthralin paste and UV exposure is called the Ingram technique. Systemic treatment Corticosteroids The use of systemic steroids can be hazardous because of the possibility of a rebound when stopped and the potential of inducing generalised pustular psoriasis. The only exception is in patients with impetigo herpetiformis. Methotrexate This folic acid antagonist is one of the more commonly used drugs in the systemic treatment of psoriasis. By reducing cell division in the epidermis and also affecting the inflammatory response, excellent results can be obtained. Indications for the use of this drug include acute pustular psoriasis, psoriatic arthritis, widespread plaque psoriasis, and psoriatic erythroderma. Patient selection is important though, and patients with a history of liver and kidney disease, alcohol abuse, haematological abnormalities, and immunodeficiency should be excluded. It is also contra-indicated during pregnancy. Routine liver function tests, kidney function tests and full blood counts should be performed. Controversy exists over the necessity of performing routine liver biopsies, since the procedure itself is not without risk. By careful selection of patients and proper follow-up, this should not be necessary and be reserved for patients where indicated. The concomitant taking of oral folic acid may be beneficial in reducing the side effect profile. Dosage varies from 7.5 mg to a maximum of 30 mg per week taken in three divided doses 12 hours apart. Cyclosporin In certain European countries like Italy, cyclosporin is the drug of choice in the systemic treatment of psoriasis. It is a potent immunosuppressant, but unfortunately with potentially serious side effects. Dosages of 2.5-5 mg/kg/day produce rapid clearing and durations of up to 6 months treatment are associated with a low incidence of renal complications. Some authors recommend intermittent short courses of 12 weeks. Routine kidney functions, full blood count, serum magnesium, potassium and uric acid, as well as a lipid profile should be performed.
SOUTH AFRICAN RHEUMATOLOGY JOURNAL September/October 2012 29 The blood pressure of the patient should also be closely monitored. Although clearance is rapid, plaques reappear rapidly when discontinued. Retinoids Acitretin as a derivate of vitamin A modulates epidermal proliferation and differentiation and is also known to have immunosuppressive and anti-inflammatory activity. Dosages of 0.25-0.5 mg/kg/day are recommended. Unfortunately, acitretin is teratogenic and contra-indicated during pregnancy. Although the half-life is relatively short (49 hours) acitretin may transform to etretinate either spontaneously or as a result of the concurrent intake of alcohol. The half-life of etretinate is much longer (168 days), and it may take up to 3 years for 98% of the etretinate to be eliminated. Therefore, treatment with acitretin is contra-indicated in women who intend to become pregnant within 2-3 years after discontinuing therapy. Routine liver functions and a lipid profile should be performed when taking this drug. Dose-related hair loss, which is reversible, may be unacceptable to some patients. Antibiotics When the presence of a streptococcal infection is suspected, i.e. exacerbation of chronic plaque psoriasis or acute guttate psoriasis, the use of an antibiotic like cloxacillin or rifampin is indicated. Biological agents A number of biological agents are available and can produce dramatic results in patients with psoriasis. All of these agents suppress the normal immune response and have the potential of serious side effects, some more than others. Tumour necrosis factor (TNF) is one of the key cytokines and acts as a primary mediator for inflammation. The synthesis of TNF, as well as other cytokines, is stringently regulated to prevent immunological responses from becoming persistent. In patients with psoriasis, higher levels of TNF immunoreactivity and biological activity are found in active lesions compared to normal skin. Elevated levels of TNF have also been detected in the synovial fluid of patients with psoriatic arthritis. However, the most convincing evidence implicating TNF in the pathogenesis of psoriasis is the dramatic response to TNF antagonists in patients with psoriasis. To neutralise TNF, agents act on different levels. Etanercept is a soluble dimeric fusion protein consisting of two molecules of the ligand binding portion of the human TNF receptor-fused to the Fc portion of human IgG1. Since it is dimeric, it has the capacity to bind two molecules of TNF. Etanercept binds to soluble and transmembrane-bound TNF, thereby inhibiting their interaction with cell surface TNF receptors. Induction therapy for the first 12 weeks at dosages of 50 mg twice-weekly as a subcutaneous injection is followed by maintenance dosages of 50 mg per week. No routine laboratory monitoring is required. Infliximab is a chimeric monoclonal antibody that binds specifically to soluble and membrane-bound TNF, therefore inhibiting the interaction between the cytokine and its receptor. It is given intravenously at dosages of 3-5 mg/kg. The side effect profile of infliximab and the possibility for production of neutralising antibodies limits its use, although clearance is achieved more rapidly compared to other products. Risks when using biologicals include serious opportunistic systemic infections, reactivation of tuberculosis, and demyelinating disease. Unfortunately, all of these drugs are still very expensive. Conclusion The course of psoriasis is very unpredictable. It is a chronic disease with the tendency to recur. Patient support and motivation is as important as the prescription the patient receives when leaving the physician s office and should not be underestimated. References available on request.