P ANDREWS’ DISEASES OF THE SKIN

P214-239 ANDREWS’ DISEASES OF THE SKIN
Seborrheic Dermatitis, Psoriasis, Recalcitrant Palmoplantar Eruptions, Pustular Dermatitis, and Erythroderma P ANDREWS’ DISEASES OF THE SKIN

Seborrheic dermatitis
2- 5 % of the population Chronic, superficial, inflammatory disease of the skin Predilection for the scalp, eyebrows, eyelids, nasolabial creases, lips, ears, sternal area, axillae, submammary folds, umbilicus, groin, and gluteal crease Characterized by scanty, loose, dry, moist, or greasy scales, and by crusted pink or yellowish patches of various shapes and sizes

Clinical features Remissions and exacerbations No to mild itching
On the scalp is the most common Pityriasis steatoides – oily type, accompanied by erythema and accumulation of thick crust Frequently spreads beyond the scalp

Extreme cases involve the entire scalp and may have an offensive odor
Cradle cap Marginal blepharitis – edges of the lids becoming erythematous and granular. Conjunctiva may be injected On and in the ears may be mistaken for otitis externa caused by a fungal infection KOH –

The presternal area is a favored site on the trunk
Common in the groin and the gluteal crease In acute stages the inflammation may be intense, with moist exudation from the scalp and ears and papulovesicles on the palms and soles. Secondary infections, impetiginization, or furunculosis may ensue

May progress to a generalized exfoliative state
In the newborn this type of severe and generalized seborrheic dermatitis is known as erythroderma desquamativum May be associated with or accentuated by several internal diseases Parkinson’s, HIV, DM,

Etiology and pathogenesis
Remains unresolved Presence of lipophilic yeast Pityrosporum ovale in large numbers in scalp lesion Also demonstrated in those without seborrheic dermatitis Healthy individuals have been found to have higher IgG antibodies to the organism

The significance of P ovale in infantile seborrheic dermatitis has not been fully evaluated
Familial tendency toward infantile and adult seborrheic dermatitis

histology Epidermis is acanthotic
There is overlying focal scale crust often adjacent to follicular ostia Slight spongiosis Dermis contains a perivascular mixed cell inflammatory infiltrate

Differential diagnosis
Psoriasis, heavier scale and erythema, Auspitz’s sign, resistance to treatment, nail involvement Crusted scabies of the scalp in immunodeficiency syndromes Otitis externa, blepharitis, tinea corporis, pityriasis rosea, keratosis lichenoides chronica

Treatment Selenium sulfide, tar, zinc, pyrithionate, resorcin shampoos
Nizoral Corticosteroid solution Antimicrobial preparations may be necessary Bifonazole shampoo has been shown effective in treating infants and small children

Cortisporin otic usually brings about prompt clearing
Desonide Otic Lotion, 0.05% Desonide and 2% acidic acid is also effective Topical steroids should not be used for blepharitis, since steroid preparations used in area may induce glaucoma and cataracts

psoriasis A common, chronic, recurrent, inflammatory disease of the skin characterized by round, circumscribed, erythematous, dry, scaling plaques of various sizes, covered by grayish white or silvery white, imbricated and lamellar scales Predilection for the scalp, nails, extensor surfaces, elbows, knees, umbilical, and sacral region

Typically symmetrical
May be a solitary macule to more than 100 Usually develops slowly but may be exanthematous, with a sudden onset of numerous guttate lesions Subjective symptoms such as itching or burning may be present and cause extreme discomfort

Scales are micaceous Auspitz’s sign may be observed Annular, lobulated, and gyrate figures may be produced Old patches may be thickened and tough, and covered with lamellar scales like the outside of an oyster shell – psoriasis ostracea

Various other descriptive terms
Psoriasis guttata Psoriasis follicularis Psoriasis figurata, psoriasis annulata, psoriasis gyrata Psoriasis discoidea Psoriasis rupioides Plaque psoriasis

Seborrheic-like psoriasis
In some cases of psoriasis prominent features of seborrheic dermatitis may occur not only if the typical sites of psoriasis vulgaris but also in the flexural areas such as the antecubital areas, axillae, under the breasts, groins, umbilicus, and intergluteal areas Sebopsoriasis or seborrheic psoriasis

Inverse psoriasis Flexural psoriasis or volar psoriasis
Selectively and almost exclusively involves folds, recesses, and flexural surfaces Scalp quite often participates as well Onycholysis, “Oil spots”, and nail pitting may be seen

“Napkin” psoriasis Diaper dermatitis caused by the irritative effects of urine in the wet diaper area, may imitate a psoriasiform eruption In addition there is commonly an infection with Candida albicans Lesions typically clear Infants may be at risk for psoriasis in adulthood

Psoriatic arthritis The incidence of psoriasis is 10 times greater in persons with seronegative arthritis than in persons without arthritis

Five clinical patterns
Asymmetrical distal interphalangeal joint involvement with nail damage, 16% Arthritis mutilans with osteolysis of phalanges and metacarpals, 5% Symmetrical polyarthritis-like rheumatoid arthritis, with claw hands, 15% Oligoarthritis with swelling and tenosynovitis of one or a few hand joints, 70% Ankylosing spondylitis alone or with peripheral arthritis, 5%

Radiographic findings suggestive of psoriatic arthritis include: erosion of terminal phalangeal tufts, tapering of phalanges or metacarpals, “cupping’ of proximal ends of phalanges, , bony ankylosis, osteolysis of metatarsals, predilection for distal and proximal interphalangeal joints, paravertebral ossification, asymmetrical sacroiliitis, and rarity of “bamboo spine”when the spine is involved Nearly half the patients with psoriatic arthritis have HLA-B27

Rest, splinting, passive motion, and aspirin or NSAIDs are appropriate
Methotrexate, cyclosporine, oral retinoids, sulfasalazine, tacrolimus, and PUVA are all likely to help both the psoriasis and arthritis Systemic steroids however, the long term complications and potential for rebound in cutaneous disease restricts their use

Guttate psoriasis This distinctive form of psoriasis typical lesions are the size of water drops Usually occurs as an abrupt eruption following some acute infection, such as streptococcal pharyngitis Occurs mostly in patients under age 30 Recurrent episodes are likely, because of pharyngeal carriage of the responsible streptococcus This type of psoriasis is usually rapidly responsive to topical steroids or UVB

Generalized pustular psoriasis (von Zumbusch)
Typical patients have had plaque psoriasis and often psoriatic arthritis The onset is sudden, with formation of lakes of pus periungally, on the palms, and at the edge of psoriatic plaques Pruritis and intense burning cause extreme discomfort There is a fever, and a fetid odor develops The pustules dry up to form yellow-brown crusts over a reddish-brown shiny surface

Mucous membrane lesions are common on the tongue and in the mouth The lips are red and scaly, and superficial ulcerations of the tongue and mouth occur May go through several stages A number of cases of acute respiratory distress syndrome associated with pustular and erythrodermic psoriasis have been reported Systemic complications include pneumonia, CHF and hepatitis

Etiology unclear Iodides, coal tar, steroid withdrawal, terbinafine, minocycline, hydroxychloroquine, acetazolamide, and salicylates may trigger the attacks May occur in infants Acitretin is drug of choice, with a rapid and predictable response Isotretinoin, cyclosporine, methotrexate, dapsone

course The course of psoriasis is unpredictable
Usually begins on the scalp or elbows May first be seen over the sacrum Onset may be sudden and widespread First lesions may be limited to the fingernails Two of the chief features of psoriasis are its tendency to recur and persist

However, patients may remain completely free of lesions for years
Koebner’s phenomenon – the appearance of typical lesions of psoriasis at sites of eve trivial injury Auspitz’s sign – pinpoint bleeding when the psoriatic scale is forcibly removed, this occurs because of severe thinning of the epidermis over the tips of the dermal papilla Woronoff ring – is concentric blanching of the erythematous skin at or near the periphery of the healing psoriatic plaque

On the scalp absence of itching or hair loss, marked predilection for frontal scalp margin, deep erythema, and resistance to effective therapy for seborrheic dermatitis all suggest psoriasis The palms and soles are often, sometimes exclusively, affected “flexural” or inverse psoriasis shows salmon-red, demarcated plaques that frequently become eczematized, moist and fissured

Numerous cases of psoriasis of the mucous membranes have been reported
Fingernails and toenails may be involved. Characteristic changes include pits, onycholysis and cracking of the free edges Many studies report an association of hepatitis C and psoriasis Hepatitis C has also been implicated in psoriatic arthritis

etiology The cause of psoriasis is still unknown
Heredity is of significance in some cases Evidence that susceptibility to psoriasis is linked to class I and II major histocompatibility complex on human chromosome 6 (17q) HLA associations include -Cw6, -B57, and -DR7 for early onset and -Cw2 for late onset psoriasis

It is believed also that any individual that has –B13 or –B17 has a fivefold risk of developing psoriasis In pustular psoriasis HLA-B27 may be seen -B13 and -B17 are increased in guttate and erythrodermic psoriasis

epidemiology Equal frequency in both sexes
Mean age of onset is 27 years, range is wide Sunlight improves Emotional stress aggravates 39% of patients experience complete periodic disappearance of psoriasis during its course Seen in 1-2% of US population. Not seen in Native Americans

Distinct tendency to improvement with pregnancy
Exacerbation is common after childbirth

pathogenesis Characterized by three main pathogenic features: abnormal differentiation, keratinocyte hyperproliferation and inflammation Accelerated epidermopoiesis has been considered to be the fundamental pathologic event in psoriasis The transit rate of psoriatic keratinocytes is increased, and the deoxyribonucleic acid synthesis time is decreased

Early lesion are infiltrated predominantly by lymphocytes in the papillary dermis
The cause of T-lymphocyte activation and the role of these cell populations remains unclear

stress Studies have shown a positive correlation between stress and the severity of disease

Drug-induced psoriasis
May be induced by many drugs: beta blockers, lithium, and antimalarials, terbinafine, calcium channel blockers, captopril, glyburide, and lipid lowering agents such as gemfibrozil

Pathology Regular epidermal hyperplasia with long, test-tube-shaped rete ridges Thinning of dermal papillae Granular layer is thin or absent Overlying parakeratosis Small collections of neutrophils (Munro microabcesses) may be present in the stratum corneum There is a perivascular mononuclear cell infiltrate

Seborrheic dermatitis, pityriasis rosea, lichen planus, eczema, psoriasiform syphilid, and lupus erythematosis Distribution, quality of the scale and presence of Auspitz’s sign, symptoms, serologic testing

treatment Topical Systemic Combination
Rotating therapeutic approaches, especially with systemic agents that have varying toxicities

Topical treatment In many patients topical applications alone will suffice to keep psoriasis under control. Numerous local medications are available

Corticosteroids Most frequent therapy Ointments are more effective
Creams are preferred in the intertriginous areas and in exposed areas Effectiveness may be augmented by an occlusive dressing, prompt response is usually noted Side effects include miliaria, pyoderma, epidermal atrophy

Intralesional corticosteroid injections
Good results when treating psoriatic nails

tars The staining property and the odor of the tars may hinder their use Coal tar or liquor carbonis detergents is applied to the lesions before ultraviolet treatment in the Goeckerman method

dihydroxyanthralin Anthralin exerts its direct effect on keratinocytes and leukocytes by suppressing neutrophil superoxide generation and inhibition of monocyte derived IL-6, IL-8, and TNF-alpha Highly irritating and stains skin, clothing and bedding

tazarotene Appears to treat psoriasis by modulating keratinocyte differentiation and hyperproliferation, as well as suppressing inflammation Produces local irritation Combination with topical corticosteroids aids in patient acceptance

Vitamin D Vitamin D3 affects keratinocyte differentiation partly through its regulation of epidermal responsiveness to calcium Has been shown to be very effective in the treatment of plaque-type and scalp psoriasis Combination therapy with high-potency steroids may provide greater response

Salicylic acid Aids in removing of the scale and promoting the efficacy of other topical agents Usually in a 3% to a 5% concentration Widespread application may lead to salicylate toxicity Tinnitus, acute confusion, refractory hypoglycemia

Ultraviolet light In most instances sunlight improves psoriasis remarkably However, burning of the skin may cause Koebner’s phenomenon and an exacerbation UVB Tar applications or baths before UVB exposure have been credited with enhancing its effects Maintenance UVB phototherapy after clearing contributes to the duration of remission

Narrow band UVB has been shown to be more effective in treating psoriasis than broadband

Goeckerman technique 2 to 5% tar preparation is applied to the skin, and a tar bath is taken at least once daily. The excess tar is removed with mineral or vegetable oil and ultraviolet light is given

Ingram technique Consists of a daily coal tar bath in a solution such as 120 ml liquor carbonis detergens to 80 L of warm water This is followed by exposure to an ultraviolet light for daily increasing periods Anthralin paste is then applied to each psoriatic plaque Talcum powder is sprinkled over the lesions, and a stockinette dressing is applied

PUVA therapy UVA given 2 hours after ingestion of 8-methoxypsoralen (Oxsoralen), and given two to three times a week Maintenance treatment is needed Risk of enhanced carcinogenesis is proven Reversal of the usual ratio of squamous cell carcinomas to basal cell carcinomas Accelerated actinic elastosis, melanocyte dysplasia, and possible increased incidence of melanoma should be considered

Surgical treatment Denervation by surgery has long been known to abolish psoriatic plaques Excision to the depth of the reticular dermis In a group of 14 patients with pharyngeal colonization by streptococci unresponsive to antibiotic therapy 9 cleared after tonsillectomy

Lasers in psoriasis Psoriatic plaques can be cleared by destruction of the upper dermis Blood vessels in the psoriatic dermal papillae can be selectively destroyed with yellow lasers effectiveness with flashlamp pulsed dye laser Some success with CO2 resurfacing laser

hyperthermia 22 chronic psoriatic plaques in 9 patients were heated to 42 – 45 C with ultrasound for 30 minutes 3 times a week for 4 to 10 treatments. 15 completely cleared Microwave hyperthermia may produce significant complications such as pain over bony prominences and hypotension

Occlusive treatment Report of clearing of psoriatic lesion by occluding them with tape Has been shown that hydrocolloid occlusion (with Actiderm) had a similar effect on small lesions

Systemic treatment Corticosteroids Methotrexate Cyclosporine Diet
Oral antimicrobial therapy Retinoids dapsone

Corticosteroids The side effects of orally administered prednisone are so dangerous that its use should be limited to patients with unusual individual circumstances There is a great risk of “rebound” or induction of pustular psoriasis when it is stopped

Methotrexate Was the first effective systemic drug for psoriasis and is the standard for systemic therapy Methotrexate has greater affinity for dihydrofolic acid reductase than has folic acid The synthesis of deoxyribonucleic acid is blocked when dihydrofolic acid reductase is bound and thereby cell division is decreased

May also affect the inflammatory elements of psoriasis
Indications for its use include psoriatic erythroderma, moderate to severe psoriatic arthritis, acute pustular psoriasis, more than 20% total body surface involvement, localized pustular psoriasis, psoriasis that affects certain areas of the body so that normal function and employment are prevented, lack of response to phototherapy, PUVA, or retinoids

Prior to start of treatment ensure that there is no history of liver or kidney disease
Alcohol abuse, cirrhosis, severe illness, debility, pregnancy, anemia should be considered AST, ALT, bilirubin, serum albumin, creatinin. Alkaline phosphatase, CBC, platelets, Hep B and C serology, and UA should all be evaluated prior to tx

Most patients with no risk factors for liver disease the first liver biopsy should be obtained at approximately 1.0 to 1.5 g of cumulative methotrexate and repeated every subsequent 1.5 g until a total of 4 g is reached 3 divided oral doses 12 hrs apart weekly, once weekly doses orally and single weekly subcutaneous injections are effective treatment schedules

Cyclosporine The therapeutic benefit of the immunosupressive features of cyclosporine in psoriatic disease may be related to down modulation of proinflammatory epidermal cytokines Biopsies of the kidney in 30 patients after 2 years of cyclosporine treatment found features consistent with cyclosporine-induced nephrotoxicity

Another study concluded that cyclosporine may be used long-term (5-10 years) in severe, recalcitrant psoriasis if renal function is closely monitored Induction of therapy with 2.5 to 3.0 mg/kg given as a divided dose twice daily and may be increased to 5.0 mg/kg/day until a clinical response is noted

Diet Controlled studies evaluating various dietary restrictions, especially those of low protein intake, showed no appreciable difference in the course of psoriasis Another study found psoriasis to be more severe in patients trying herbal remedies, vitamin therapy, and dietary manipulation

Most recent trials have demonstrated the antiinflammatory effects of fish oils rich in n-3 polyunsaturated fatty acids in rheumatoid arthritis, inflammatory bowel disease, psoriasis and asthma

Oral antimicrobial therapy
Recent evidence suggest that Staphylococcus aureus and streptococci secrete a large family of exotoxins that are superantigens, producing massive T-cell activation Oral antibiotic for psoriasis patients infected with these organisms is imperative

Retinoids Treatment with 13-cis-retinoic acid can produce good results, especially in pustular psoriasis It is a potent teratogen Combinations of retinoic acids with photochemotherapy for chronic plaque psoriasis may also be very affective Etretinate Acitretin, avoid pregnancy for up to 3 years following cessation of therapy

dapsone Use is limited largely to palmoplantar eruptions

Combination therapy Patient on methotrexate may have their dose minimized with concomitant topical steroid use PUVA with Acitretin PUVA with cyclosporine PUVA with methotrexate Topical Dovonex with Acitretin, cyclosporine, methotrexate, and phototherapy

The principle behind combination therapy is the use of agents win which the side effects profile is different or partly opposing Hydroxyurea and sulfalsalazine have been used in severe cases and in combination with other modalities, such as PUVA Particularly useful in topical therapy, where the risk profiles are considerably less

Reiter’s syndrome Characteristic clinical triad consisting of urethritis, conjunctivitis, and arthritis May also be other features that involve the skin , mucous membranes, gi tract, and cardiovascular system American Rheumatism Association criterion of peripheral arthritis of more than 1 month duration, in association with urethritis and/or cervicitis Occurs chiefly in young men of HLA-B27 genotype

Clinical features Any one of the triad of urethritis, conjunctivitis, or arthritis may occur first, accompanied by fever, weakness, and weight loss. A nonbacterial urethritis may develop with painful and bloody urination and pyuria About 1/3 of patients develop conjunctivitis Keratitis is usually superficial and very painful. Iritis is common

An asymmetric arthritis afflicts synovial joints, especially those that are weight bearing
Onset is sudden with heat and tenderness and swelling Pain in one or both heels is a frequent symptom

The skin lesions start as multiple, small, yellowish vesicles that break, become confluent and form superficial erosions Develop frequently on the genitals and palms Eruption on the glans penis occurs in 25% of patients Lesions on the soles start as pustules, become crusted or hyperkeratotic

The eruption is known as keratoderma blennorrhagicum
Penile lesions are frequent Characterized by perimeatal balanitis, these become crusted and form circinate lesions Similar lesion are seen on the vaginal mucosa of women

Nails become thick and brittle, with development of subungal keratosis
Endocarditis, pericarditis, and myocarditis, as well as aortic insufficiency occur in some In children conjunctivitis is the most frequent complaint

etiology Syndrome has been attributed to many different agents such as Shigella flexneri, Salmonella spp., yersinia spp., Ureaplasma urealyticum, Borrelia burgdorferi, Cryptosporidia, and Campylobacter fetus May be responsible for the infectious enteritis that precedes onset in a small percentage of patients In cases that follow an infection of the genitourinary tract, Chlamydia trachomatis may be associated

HLA-B27 positivity is present in 80% of cases of Reiter’s syndrome
This rises to 90 to 100% in patients with accompanying sacroiliitis, uveitis, or aortitis May be caused by abnormalities in the production and elicitation of immune mediators or T cells

Laboratory findings No specific changes are characteristic of this syndrome A leukocytosis of 10, 000 to 20, 000/mm3 and an elevated sed rate are the most consistent findings

histopathology Identical to psoriasis

May be confused with rheumatoid arthritis, ankylosing spondylitis, gout, psoriatic arthritis, gonococcal arthritis, acute rheumatic fever, chronic mucocutaneous candidiasis, and serum sickness

treatment Usually mucocutaneous lesions are self limited and clear within a few months Topical steroids are helpful NSAIDs for the joint disease Methotrexate for severe disease Cyclosporine Acitretin

The course is characterized by exacerbations and remission in about on third of patients
A chronic deforming arthritis occurs in a bout 20% of patients, with significant disability resulting, chiefly from foot deformities

Subcorneal pustular dermatosis (Sneddon-Wilkinson Disease)
Chronic pustular disease which occurs chiefly in middle-aged women. Pustules are superficial and arranged in annular and serpiginous patterns, especially on the abdomen, axillae and groins Sometimes vesicles are present Cultures from pustules are sterile Oral lesions are rare Some cases occur in association with and IgA monoclonal gammopathy

Subcorneal pustular dermatosis (Sneddon-Wilkinson Disease)
Dapsone appears to be effective in most cases Sulfapyridine Acitretin Narrow band UVB Corticosteroids, colchicine, and TCN with niacinamide Without treatment this is a chronic condition with remissions of variable duration

Eosinophilic pustular folliculitis
Also referred to as sterile eosinophilic pustulosis Five times more common in males Peak age of onset in the third decade, although a number of pediatric cases have been reported Characterized by pruritic, follicular papulopustules arranged in groups Plaques may form

Distribution is usually asymmetrical, with the face, trunk, and upper extremities most often afflicted Cause is unknown, however, numerous studies have implicated chemotactic substances, ICAM-1, and cyclooxygenase-generated metabolites Typical course is one of spontaneous remissions and exacerbations lasting from a few months to several years

Dapsone or systemic steroids are the treatment of choice Success with intralesional steroids, clofazimine, minocycline, isotretinoin, UVB therapy, indomethacin, colchicine, cyclosporine, and cetirizine Must be distinguished from HIV-associated EF

Another variant has been described that occurs early in childhood Patients develop sterile pustules and papules preferentially over the scalp and; however, scattered clusters of pustules may occur over the trunk and extremities High-potency topical steroids are the treatment of choice Recurrent exacerbations and remissions usually occur with spontaneous remission

P ANDREWS’ DISEASES OF THE SKIN

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P ANDREWS’ DISEASES OF THE SKIN

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