observed on digits. About 35% of patients are ANA posi- tive. Only 6.5% progress to SLE, wh ich is more likely if they are ANA positive. Treatment: sunscreen, topical/intra- lesional GCs, antimalarials, gold salts, dapsone, thalidomide, and efalizumab. Rheumatoid arthritis Rheumatoid nodules The most common extra-articular manifestation of rh eumatoid arthritis (RA). \200 Subacute cutaneous lupus (SACLE) Diffuse erythematosus papules and scales or annular polycy clic (ring-like) erythema on neck, trunk, and arms. Exacerbated by UV light. 80% are positi ve for Ro/SS-A antibodies, 60% are ANA positive. 50% patients ful \201 l SLE ACR criteria usually on dermatological and serological grounds only. Transformation into SLE with modera te disease activity in 10 \200\22315 %. Treatment as for DLE. 90% of patients with rheumatoid nodules will be rheumatoid factor (RF) positive. Distributi on: extensor surfaces of the forearm, \201 ngers, occiput, back, and heel. Histology: gra nulomas with plasma cells, lymphocytes and histiocytes. Methotrexate-induced accelerated rh eumatoid nodulosis is well recognized and resolves with cessation of meth- otrexate. A simi lar phenomenon has been reported with etanercept. Lupus panniculitus/profundus Deep dermal and subcutaneous nodules with normal over- lying s kin (although characteristic lupus histology is found in overlying dermis). Heals with lipo atrophy. ANA positive 75%. Uncommonly transforms into SLE. Acute cutaneous lupus erythematosus (ACLE) Butter \202 y erythema. Diffuse erythema/maculo papular rash. Heals without scarring. Oral ulceration. Diffuse non- scarring alopecia. Phot osensitivity. Almost always ANA positive and 40 \200\22390% of patients are dsDNA positive. Often accompanies flare of systemic disease. Treatment: sunscreen, topical GCs, systemic S LE treatment. Rheumatoid cutaneous vasculitis Incidence of 2 \200\22310% in patients with RA, more common in males and RF positive patients. \200 Features in order of incidence are: cutaneous ulcers, purpura, nail-fold vasculopathy, non- speci \201 c nodular erythema, haemorrhagic blisters, livedo reticularis and erythema elev atum diutinum (red/purple nodules and plaques on extensor surfaces). Treatment is with gluc ocorticoids (GCs) and other immunosuppressants. The differential diagnosis of cutaneous ulc ers is large. Lower leg ulceration in a patient with RA is more likely to be due to venous ulceration. Dermatological advice should be sought before starting systemic treatment for c utaneous ulceration. Rare clinical sub-types Chilblain lupus erythematosus Peripheral painful nodules; 20% progr ess to SLE. \200 Neonatal cutaneous lupus Transient cutaneous lupus secondary to placental transfer of antib odies. Bullous lupus erythematosus Diffuse bullous lesions associated with active SLE. Granulomatous dermatitis This condition is rare, but usually associated with RA, although i t can be seen in other autoimmune connective tissue diseases (AICTDs). \200 Lupus erythematosus tumidus Urticarial plaques on sun exposed areas. Rowell syndrome. Erythema multiforme-like lesions. ANA positive \200\223 speckled pattern IF, anti-La antibodies and usually RF positive. The rash is erythematous to violaceous indurated linear cords (Rope sign). Rash is usually symmetrical extending from the axilla to the mid-back, but can occur anywhere. Antiphospholipid syndrome (APLS) Cutaneous \201 ndings in this condition have been descri bed with the following frequency: \200 Livedo reticularis 24%. \200 Leg ulcers 5.5%. \200 Pseudovasculitis 3.9%. \200 Cutaneous necrosis 2.1%. \200 Splinter hemorrhages 0. 7%. Patients with a very similar cutaneous presentation without laboratory evidence of APLS may have Sneddon \200\231s syndrome. The pathogenesis of this disease is unclear and the r elationship to lupus/APLS is controversial. Cutaneous lupus erythematosus Cutaneous lupus erythematosus is not synonymous with cutaneou s manifestations of systemic lupus erythematosus (SLE). Distinct dermatological patterns of cutaneous lupus exist and the majority of patients with cutaneous lupus do not progress to SLE. Dermatological (American Rheuma- tology Association; ARA) criteria include malar rash , discoid rash, photosensitivity, and oral ulcers (see Plate 12). It is therefore possible to meet ARA criteria on dermato- logical signs only. However, some would argue that malar r ash and photosensitivity are one and the same. Histology and direct immuno \202 uorescence (IF) are often similar, but not identical in the different types of cutaneous lupus. Dermatomyositis Cutaneous features of dermatomyositis (DM) are charac- teristic and, in wel l developed cases, diagnostic. \200 Discoid lupus erythematous (DLE) Well-de \201 ned scaly plaques of variable size frequentl y in- volving the face. Scarring alopecia, atrophy, and pigmentary changes. Healing occurs with scarring. Can mimic rosacea. Exacerbated by UV light. Chilblain-like lesions often Classical cutaneous features include heliotrope rash (peri-ocular purple macular rash), eye lid oedema, photosensitivity, erythematosus papules over knuckles (Gottron \200\231s papule s), linear erythema over fingers, CHAPTER 3 Organ involvement in rheumatological disease 99 dilated/tortuous nail-fold capillaries, ragged cuticles, poikiloderma in a photosensitive d istribution, cutaneous calci \201 cation and erythema of extensor aspect of knees and elbo ws. Non-classical cutaneous features include exfolative dermatitis, gingival telangiectasia (juvenile DM), \202 agellate erythema, bullae, erythema nodosum, urticaria, psoarisi- fo rm plaques, livedo reticularis, and erythema multiforme. SACLE and DM cutaneous signs are o ften dif \201 cult to differentiate. DM often exhibits erythema on the upper eyelids and n asolabial folds, whereas SACLE does not. Cutaneous features precede myositis in 30% of case s. Amyopathic dermatomyositis (ADM) is being increas- ingly recognized as a presentation. P rogression to classical DM is not inevitable. Patients can have exclusively cuta- neous dis ease for over 5 years. A positive ANA is found in 63% of ADM patients, but only 3.5% have m yositis-speci \201 c autoantibodies (e.g. Jo-1, Mi-2). ADM is not a benign condition and i s associated with interstitial lung disease in 13% of cases. Cutaneous treatment includes s unscreen (UV exposure may exacerbate myositis), topical GCs/calcineurin inhibitors. Systemi c GCs and other immunosuppressants are often required. Cutaneous calcinosis Often digital calcinosis progresses to digital ulcers. A minority of p atients have sheets of cutaneous calcinosis over the trunk and limbs leading to extensive u lceration. Can be treated by a carbon dioxide laser and surgery. Localized scleroderma (morphea) Localized scleroderma is a skin-limited disease that rarely displays systemic involvement. It is included in this chapter as it is commonly mistaken f or SSc. \200 There is little evidence to support morphea as part of a spectrum of SSc. Morphea can be di stinguished from SSc by clinical signs and autoantibody pro \201 le. Individuals with morp hea rarely exhibit Raynaud \200\231s phe- nomenon and do not have nail-fold capillary chang es. Importantly morphea very rarely progresses to SSc. There are a number of recognized sub types of morphoea, brie \202 y reviewed below. \200 \200 Plaque morphea Plaques on trunk, face, and limbs. Well-de \201 ned erythematous indurated plaque with violaceous border. Resolves with atrophy and pigmentatory changes. Generalized morphea Feature of 13% of patients with morphea. Insidious onset and can progre ss to involve large surface area. This type of morphea is often mistaken for SSc. Not assoc iated with systemic complications. Localized scleroderma and systemic sclerosis (SSc) Scleroderma is not synonymous with syste mic sclerosis (SSc). Scleroderma is a dermatological sign de \201 ned as thickening and in duration of the skin caused by new colla- gen formation with atrophy of pilosebaceous folli cles. SSc is also covered in detail elsewhere in this book (p. 264 \200\223272). This secti on will be concerned with cutane- ous signs, differential diagnosis, and the dermatological approach to a patient with types of scleroderma. Atrophoderma of Pasini and Pierini Depressed blue-brown macules lacking induration, and inf lammatory features found on trunk and proximal extremities. Linear morphea Linear morphea often extends to sub-cutaneous tissues and includes the en co up de saber phenotype. Common variant in children. Most likely sub-type to progress to SSc, although still rare. 50% have articular disease. Cutaneous signs of SSc Cutaneous systemic sclerosis usually follows three distinct phases p rogressively. \200 Deep morphea Diffuse morphea affecting sub-cutaneous structures. Several clinical variants of which eosinophilic fasciitis is the most common (see p. 310). Eosinophilic fasciitis usu ally occurs at the extremities primarily with involvement of the fascia. Linear depression along super \201 cial veins (groove sign) often present. Associated with eosinophilia. Oedematous phase: cutaneous oedema, especially \201 ngers. Can be pitting or non-pitting. A minority do not progress beyond this stage. Indurative phase: increased skin thickening representing increased collagen in the dermis. Skin is shiny and the epidermis is thinned. There is a loss of adenexal struc- tures and the skin becomes hairless and anhidrotic. Pigm entatory changes can occur. Typical facial changes of pinched nose and microstomia. Limited cutaneous scleroderma exhibits facial telangiectasia. Atrophic phase: the dermis and epide rmis become thinned. The dermis is adherent to the subcutaneous fat giving the impression t hat the skin is thickened. The differential diagnosis of scleroderma There are many scleroderma and scleroderma-like d erma- tological conditions that mimic SSc and should be excluded. Skin biopsy is recommende d in the investigation of scleroderma. The most common of these conditions are described be low. Scleromyxoedema (papular mucinosis) Waxy papules with marked skin sclerosis on face, neck, and dorsum of hands. Histologically cutaneous mucin depositions. Associated with paraprotei naemia. Nail-fold changes Dermatologists use a dermatoscope to assess nail-fold changes as part of a routine examination. Enlarged loops, hemorrhages, angiogenesis, loss of capillaries, and avascu- lar areas characterize more than 95% of patients with overt SSc. Buschke scleredema Symmetrical indurated skin often on neck extending to face and upper lim bs. Deposition of dermal mucopolysac- charide associated with streptococcal infection, diab etes, and paraproteinaemia. Raynaud \200\231s phenomenon Capillary nail-fold changes are useful in distinguishing pri- mary Raynaud \200\231s phenomenon from secondary Raynaud \200\231s phenomenon. THE SKIN 100 Vasculitis is commonly clinically suspected by the presence of palpable non-blanching purpu ra, but this is not pathognomonic of cutaneous vasculitis. An differential diagnosis of pur pura includes: \200 \200 \200 Nephrogenic \201 brosing dermopathy Symmetrical sclerotic plaques over thighs, forearms, and trunk. Patients usually have end-stage renal failure and have had gadolinium radiologic al contrast administration in the months preceding onset of symptoms. platelet disorders; coagulation disorder; dysproteinamias \200\223 Sj gren \200\231s synd rome, Waldenstrom \200\231s cryoproteinnaemias; emboli \200\223 fat, crystal, infective; r aised intravascular pressure: coughing, venous stasis; loss of dermal support: steroid purp ura, senile purpura; inherited collagen disorders; capillaritis (pigmented purpuric dermato ses); solar purpura; scurvy. Porphyria cutanea tarda Clinically and histologically can be identical to SSc cutaneous dis ease. A history photosensitivity, blistering, hyperpigmen- tation, skin fragility, and hype rtrichosis should prompt further investigation. \200 \200 \200 \200 \200 \200 Confusingly, cutaneous vasculitis can present as petechiae, urticaria (urticarial vasculitis), large brown nodules on extensor surfaces (ery thema elevatum diuti- nium), facial asymptomatic plaques (granuloma faciale), suppurative s ub-cutaneous nodules of the thighs (ery- thema induratum) livedo reticularis with gangrene (cuta- neous polyarteritis nodosa), and cutaneous ulceration to name, but a few. All these dermatological patterns of vasculitis have distinct disease associations and natural histor y. The diagnosis of vasculitis should always be con \201 rmed on histology. The determinat ion of the cutaneous sub-type of vasculitis is usually then made clinically. Biopsy should be taken between 12 and 24 h from onset of lesion, either punch biopsy for suspected dermal vasculitis, or deep incisional biopsy for suspected sub- cutaneous vasculitis. Direct IF ( DIF) can be helpful in suspected Henoch \200\223 Sch nlein purpura (HSP). Perivascular IgA deposits are characteristic but not exclusive to HSP. A persistent rash or heavy depositio n of IgA in the skin is thought to be a prognostic sign for renal disease. For other vascul itides DIF is non-speci \201 c. POEMS syndrome Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and ski n changes. Variable scleroderma-like changes with marked hyperpigmentation. Diabetes mellitus Symmetrical, bilateral thickening, and induration of the skin on the dors um of the \201 ngers with subsequent progressive contractures of \201 nger joints (pray er sign). Oedema and Raynaud \200\231s phenomenon not observed. Stiff skin syndrome Sclerotic changes over buttocks and thighs from infancy. Recessive and dominant genetic inheritance. Good prog- nosis with no systemic involvement. Fibroblastic rheumatism First recognized as a separate clinical entity in 1980. Cutaneous n odules over the extensors and neck precede a symmetrical destructive polyarthritis. Raynaud \200\231s and skin thickening occur. It is differentiated from scleroderma as histology sh ows reduction in collagen and hyperplastic myofibroblasts. No effective treatment establish ed, although spontaneous resolution is not uncommon. Other conditions Rare differentials include: \200 \200 \200 \200 \200 \200 \200 Eosinophilia \200\223myalgia syndrome Carcinoid syndrome Toxic oil syndrome Phenylketonuria Chronic graft vs. host disease; Scleroatrophic Huriez syndrome; Werner s syndrome. Sj gren \200\231s syndrome (SS) Dermatological manifestations of SS are variable. Many pat ients have a dry skin, with lichenification present. Annular erythema occurs, and can be ra ised and almost pustular. Ro-antibody positive patients often exhibit photo- sensitive poly cyclic erythema similar to SACLE. Sweating is often impaired or absent in affected skin. Na il-fold changes occur. A minority of patients have a non-scarring alopecia. Treatment of cutaneous SSc and morphea \200 \200 \200 \200 \200 \200 Topical GCs. Topical imiquimod (toll-like receptor 7 agonist). Topical retinoids. UVA1 (340 \200\223400 nm) phototherapy. Carbon dioxide ablation of cutaneous calcinosis. Systemic im munosuppressants (particularly methotrexate) are used for severe morphea, but evidence is a necdotal. Sarcoidosis Skin disease occurs in 9 \200\22337% of sarcoid patients. It is not uncommon to \201 nd cutaneous sarcoid with little systemic involvement. Cutaneous sarcoidosis may ap pear as mac- ules, papules, patches, plaques, violaceous areas, localized alopecia, ichthyo tic areas, psoriaform plaques, subcutane- ous nodules, ulcers, and even pustules. There are three main types of cutaneous sarcoid noted. Cutaneous vasculitis (see also p. 313) Cutaneous vasculitis is a common presenting complain t in dermatology. The vast majority of these patients fall into the cutaneous small vessel vasculitis (CSVV) classi \201 cation of the Chapel Hill Consensus Conference on vasculitis . These patients have no systemic disease, serology is nega- tive, and patients often have a proceeding exposure to drugs or infectious agents. Most patients resolve spontane- ously. This section will deal with differential diagnosis of and investigation of cutaneous vascu litis from a dermato- logical viewpoint. Lupus pernio Symmetric, violaceous, indurated plaque-like, and nodular \201 brotic lesion s that occur on the nose, ear lobes, cheeks, and digits. This pattern carries a greater ris k of extensive pulmonary involvement. CHAPTER 3 Organ involvement in rheumatological disease 101 feature with oral and genital ulceration. Differential diagnosis includes mucosal and genit al ulceration with in \202 amed cartilage (MAGIC) syndrome. Skin signs include small pustu les at the extremities, sometimes with sub-corneal abscesses. Erythema nodosum-like lesions are common. About 55% of patients have a predominantly non-erosive arthritis. Scar sarcoid Occurs as the only form of cutaneous sarcoid in 30% of patients. Violaceous pa lpable hue over scars, tattoos, cosmetic \201 llers, etc. It is important to examine scar s carefully in patients in whom sarcoid is suspected. Papular sarcoid Small 2 \200\2235 mm papules symmetrically on face with predilection for pe ri-orbital skin. Dermoscopy reveals a characteristic yellow brown discolouration. Blind loop dermatosis-arthritis syndrome Associated with bowel surgery (particularly blind loop for- mation) and in \202 ammatory bowel disease. Usually, evolves over hours to days with erythema nodosum-like lesions. Rarely pustulates. Associated with non-erosive arthralg ia (?enthesitis) and fever. Some evidence may be part of the SpA spectrum of diseases. Hereditary periodic fever syndromes Cutaneous features are not uncommon in this spectrum of systemic disorders Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) Migratory macular eryth ema, conjunctivitis, oedematous dermal plaque. Cutaneous signs usually present before 2 yea rs of age and accompanied by fever. Psoriasis vulgaris Psoriasis is a common disease with 2% of the world \200\231s population affected. 90% of patients have plaque psoriasis. The basic pathology of skin psoriasis invo lves increased keratinocyte growth, angiogenesis, and lymphocyte migra- tion. Normal kerati nocytes have a life cycle of 70 days; for psoriatic keratinocytes this is reduced to 6 days . Psoriasis has recently been classi \201 ed into separate clinical entities according to phenotype. Familial Mediterranean fever Charcteristic erysipelas like rash and occasionally cutane- ou s vasculitis. Hyperimmunoglobulin D syndrome with periodic fever. Small erythematous macules, papules, an d nodules. Petechiae and purpura are also seen during attacks. Entities of psoriasis Large plaque psoriasis Characterized by red scaly well-de \201 ned p laques from 5 mm to large areas over the trunk and limbs. Occasionally only have an active edge, with normal skin in the center of the lesion, termed \200\230annular \200\231 lesion s. Muckle \200\223Wells syndrome. Cold-induced non-pruritic urticaria. Neutrophilic dermatoses The neutrophilic dermatoses comprise a group of disor- ders charact erized by recruitment of polymorphonuclear leukocytes to various layers of the skin. They o ften have systemic involvement, usually arthritis. Flexural psoriasis Occurs in axillae and groins. Well-de \201 ned, often macular erythema with minimal scale. Fissured and often painful. Pyoderma gangrenosum Clinical features include painful ulcers with overhanging violaceous e dges. Exhibits pathergy. About 40% of patients have arthritis, typically erosive and symmet rical, affecting large and small joints. In 50% of patients the disease is idiopathic. Comm on associations include hematological malignancy, in \202 ammatory bowel disease and RA. Seborrhoeic psoriasis Similar morphology to \202 exural psoriasis. Distribution is over n ose, cheeks eyebrows, and nasolabial folds. It is often dif \201 cult to differentiate bet ween seborrhoeic psoriasis and seborrhoeic dermatitis. Scalp psoriasis The scalp is the most common site involved in psoriasis. Varied morphology of lesions from large thick plaques to mild scaling. Distribution is often over occiput, an terior hairline, and posterior auricular. Often asymmetrical. Acne fulminans Severe cystic acne accompanied by fever, leukocytosis, and arthritis. Destru ctive arthropathy can occur with osteo- lytic lesions around the anterior chest wall. See a lso section on SAPHO (p. 236 \200\223237). May be exacerbated by systemic retinoids. Treatm ent; systemic GCs. \200 Guttate psoriasis Small papules and plaques less than 10 mm occurring mainly over the trunk , but can spread to face and limbs. 70% of patients presenting acutely will have evidence o f recent streptococcal infection. Antibiotic therapy can has- ten clearance. Some patients progress to chronic plaque psoriasis, but the majority have spontaneous resolution within 3 months, with subsequent \202 ares if infected by streptococcal bacteria. Patients with SAPHO can have palmoplantar pustulosis, aseptic discitis, osteitis, synovitis , and enthesitis. SAPHO arthropathy can respond to treatment with tetracyclines and NSAIDs. Sweet \200\231s syndrome Sweet \200\231s syndrome (acute febrile neutrophilic dermatosis) i s characterized clinically by painful, erythematosus pustules, and plaques with fever. \200 \200 Acrodermatitis continua of Hallopeau Erythema and scaling in a distal acral distribution (s tarting at the \201 ngers and toes, and progressing proximally) often involving the nails and nail folds. Often accompanies other forms of psoriasis and DIP joint disease. Histology shows a dense neutrophilic in \201 ltrate. Asymmetric non-erosive large joint ar thritis occurs in 10% of cases. Associated with upper respiratory tract infection, in \202 am- matory bowel disease, malignancy, RA, and sarcoid. Nail psoriasis Occurs in 40% of psoriasis patients. Many patients have nail psoriasis exclu sively. Thought to be secondary to an enthesitis adjacent to the nail matrix. This may expl ain why DIP disease and nail psoriasis often co-exist. Nail signs in Beh et \200\231s disease This disease is dealed with in detail elsewhere (see p. 340 \200 \223341). Mucocutaneous manifestations are the usual presenting THE SKIN 102 Hydroxyurea An unlicensed application of the drug, but it can be effective in moderate psor iasis. Full blood count and ANA monitoring required. psoriasis include pitting, onycholysis (lifting of the nail plate), sub-ungual hyperkeratos is, and oil spots. If there is diagnostic doubt nail biopsy may be helpful. Generalized pustular psoriasis Con \202 uent sheets of small pustules over the entire body . This can be provoked by sudden withdrawal of glucocorti- coids in patients with classical plaque psoriasis. Patients are often systemically unwell. Dermatological emergency, condit ion can be fatal. Fumaric acid esters Unlicensed in the UK, these are given orally and have good ef \201 cac y. Unknown mechanism of action. Gastrointestinal side effects. First line systemic treatmen t in Germany and Switzerland. Erythroderma Con \202 uent psoriasis affecting 90% or more of the body. Often is macular e rythema only and biopsy is required to differentiate between other dermatological disease i ncluding eczema and cutaneous T-cell lymphoma. Potentially fatal. Retinoids These drugs bind to nuclear hormone receptors in kerati- nocytes and alter growth and differentiation of the cell. \200 \200 \200 \200 The retinoid given in psoriasis is often acitretin. Particularly useful in hyperkeratotic p soriasis. Synergistic effect with nUVB and PUVA. High teratogenicity and potential long hal f-life mean that it is rarely given to menstruating women. Other side effects include dry s kin, skin fragility, hepatitis, and dyslipidemia. Palmoplantar pustulosis Pustules on palms and soles of feet that do not spread onto the bod y. 20% of patients have co-existing plaque psoriasis. Palmoplantar pustulosis is now consid ered a distinct disease entity separate to psoriasis and is no longer included in the class i \201 cation of psoriasis. Ciclosporin Used at 2 \200\2235 mg/kg. Effective within days and has excellent ef \201 cac y. In patients that have received PUVA in the past, the risk of squamous cell carcinoma (SC C) of the skin is 40-fold greater than the general population. After 10 years administratio n SCC rates are between 100- and 200-fold greater than the general population. Other side e ffects include renal failure, dyslipidemia, peripheral neuropathy, and gum hyperplasia. Table 3.14 Objective measurement tools for psoriasis Tool Psoriasis Area Severity Index (PASI) A score out of 30; a score of 10 or more being classed as severe. Dermatology Life Quality Index (DLQI) A simple 10-question validated Quality of Life questionnaire Methotrexate Used at doses between 5 and 25 mg per week. \200 The vast majority of research is based on classical large plaque psoriasis. Psoriasis has b een shown to affect health- related quality of life to an extent similar to the effects of other chronic diseases such as depression, myocardial infarction, hypertension, congestive heart failure, or type 2 diabetes. Similar ef \201 cacy to ciclosporin, but can take weeks until onset of action. Side effect s include hepatitis and cirrhosis, nausea, and bone marrow suppression. The psoriasis patie nt population is different to the rheu- matoid arthritis population; the psoriasis populati on have a much higher rate of liver disease prior to meth- otrexate administration, possibl y because of excessive weight and alcohol consumption in this population. Pro-collagen III N terminal peptide (PIIINP) assay is used to monitor for hepatic \201 brosis routinely in psoriasis patients. Treatment of psoriasis Topical treatment Topical glucocorticoids, retinoids, vitamin D anal ogs, and coal tar (coal tar extracts, e.g. dithranol). Emollients. Phototherapy Ultraviolet B radiation (UVB) (315 \200\223280 nm). Many units now use narrow band UVB (nUVB; 311 \200\223312 nm) as this has a better side effect pro \201 le. Given th ree times a week for 20 \200\22330 exposures. Anti-TNFA therapies Etanercept, adalimumab, and infliximab are currently licensed in the UK for psoriasis. NICE guidance has been issued for these drugs. Ef \201 cacy is similar to ciclosporin and methotrexate. Side effects are described elsewhere (see p. 566) Photochemotherapy: Psoralen and UVA treatment (PUVA). \200 The patient is administered psoralen orally or topically before exposure to UVA (380 \200 \223315 nm). The psoralen sensitizes the skin to ultraviolet radiation. Burning can occur w ith only seconds of exposure time. Patients must protect themselves with sunblock and UV pr otective spectacles for 24 h after systemic psoralen administration. Although more effectiv e than nUVB patients have a higher risk of subsequent skin cancer, especially if on an immu nosuppressant and so is generally not favored as \201 rst line treatment. \200 \200 Anti-T-cell therapies Alefacept and efalizumab are T cell inhibitors that have good ef \201 cacy in skin psoriasis. \200 \200 They have no effect on psoriatic arthritis. There may be less risk of re-activating mycobac terium tuberculosis (MTB) with these therapies compared with anti-TNFA therapies. Efaluzima b can cause thrombocytopenia and regular laboratory monitoring is required. Laser Excimer and pulse dye laser have been shown to improve plaque psoriasis. They are, ho wever, labor-intensive and expensive, and not generally available in the U.K. Anti-interleukin 12/23 Ustekinumab is due to gain a UK license in 2009. It is the \201 rs t \200\230biological \200\231 therapy designed speci \201 cally for psoriasis. In trials is has achieved a 90% reduction in scores in 70% CHAPTER 3 Organ involvement in rheumatological disease 103 of patients \200\223 a much better rate than is seen with other agents currently available . Safety pro \201 le is comparable to placebo. It is effective in psoriatic arthritis. Kaye BR, Kaye RL, Bobrove A. Rheumatoid nodules. Review of the spectrum of associated condi tions and proposal of a new classi \201 - cation, with a report of four seronegative cases . Am J Med 1984; 76: 279 \200\22392. Further reading Chen KR, Carlson JA. Clinical approach to cutaneous vasculitis. Am Martini G, Foeldvari I, Russo R, et al. Juvenile Scleroderma Working Group of the Pediatric Rheumatology European Society. Systemic sclerosis in childhood: clinical and immunologic f eatures of 153 patients in an international database. Arthritis Rheum. 2006; 54: 3971 \200 \2238. J Clin Dermatol 2008; 9(2): 71 \200\22392. Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD. A systematic review of adult-on set clinically amyopathic dermat- omyositis (dermatomyositis sin myositis): a missing lin k within the spectrum of the idiopathic in \202 ammatory myopathies. J Am Acad Dermatol 20 06; 54: 597 \200\223613. Roth \201 eld N, Sontheimer RD, Bernstein M. Lupus erythematosus: systemic and cutaneous m anifestations. Clin Dermatol 2006; 24(5): 348 \200\22362. Grif \201 ths CE, Christophers E, et al. A classi \201 cation of psoriasis vulgaris accor ding to phenotype. Br J Dermatol 2007;156: 258 \200\22362. This page intentionally left blank 105 Chapter 4 Rheumatological procedures: injection therapy Aspiration of joints 106 Procedure 108 ASPIRATION OF JOINTS 106 Aspiration of joints Aspiration of joints and local injections are commonly performed in rheumatological practic e and are used diag- nostically, as well as therapeutically. Injections are under- taken fo r a wide range of soft tissue and joint conditions. Tissue atrophy. Soft tissue atrophy or hypopigmenta- tion can occur after one injection, bu t is more associated with multiple injections. It is most commonly seen after subcutaneous injection and is irreversible. Anecdotally, it is commoner with longer-acting steroid prepa rations. Tendon rupture. There are case reports of tendon rupture following injection of st eroid, but it remains to be clari \201 ed if these symptomatic tendons may have ruptured a nyway. Post-injection \202 are. A \202 are of joint pain may occur in the 24 \200\22348 h following injection, and examination con- \201 rms a warm and sometime swollen joint i n severe cases. Steroid is crystalline and it is likely that small crys- talline deposits f orm in the soft tissues causing transient symptoms. The differential diagnosis is iatrogeni c septic arthritis. Osteonecrosis/steroid arthropathy. There is little evidence to support the development of a steroid arthropathy resulting from repeated steroid injections, and 2- year data in patients receiving knee injections at 3-monthly intervals found no acceleratio n in cartilage loss compared with the control group. Hypersensitivity. Hypersensitivity may arise as a result of repeated infection with a more severe in \202 ammatory reaction to r epeated injections. Facial \202 ushing. This is a common side effect and occurs shortly a fter the injection. It is transient and commoner with larger doses of steroid. Hyperglycaem ia in diabetics. Steroid injections can cause a transient rise in blood sugars, and injecti ons should therefore be planned in advance in brittle diabetics. Suppression of the hypotha lamic/pituitary axis. This is rarely a problem in clinical practice. Aspiration is diagnostic and mandatory in patients with suspected septic arthritis. It is a lso recommended if patients have crystal arthritis or haemarthosis. Aspiration is therapeut ic in patients with tense effusions, to remove irritants such as pus, which damages cartila ge and to facili- tate joint lavage in septic arthritis. Injectable therapies \200 The commonest injected agents are local anesthetic and steroid therapy. There is evidence t o support use of steroids in in \202 ammatory arthritis and osteoarthritis, as well as som e soft tissue conditions. However, because steroid injections have been used for many years in routine practice, the evidence base is less robust than for newer therapies, which have been introduced more recently. Sclerosants have been used for many years in the treat- men t of soft tissue and spinal disease, despite a limited evidence base for their ef \201 cac y. Hyalgan therapy has a role in the treatment of early osteoarthritis, but is not currentl y supported by National Institute of Clinical Excellence (NICE). More novel agents include autologous blood, botulinum toxin, and heparin. However, the evidence base for these therap ies is poor and no randomized controlled trials have been published to date. Route of injection Injections may be delivered into: \200 \200 \200 \200 Joints. Tendon sheaths. Bursae. Muscle. Injections may also be delivered around nerves to i nduce nerve blockade. Tendons are structurally hard and injecting substances into tendons i s therefore dif \201 cult. Dry-needling tendons has a role in the treatment of calci \201 c tendinitis, and plantar fasciitis. Dry needling is believed to induce a local in \202 a mmatory reaction, which then is then followed by tissue regeneration. Indications for injections Magnetic resonance (MR) studies have con \201 rmed the ef \201 cacy of intra-articular steroid injection in reducing syno- vitis in rheumatoid arthritis. The effect of the steroid is greater if arthrocentesis is performed prior to administratio n of the steroid and the joint aspirated to dryness. In osteo- arthritis, the largest liter ature surrounds injections into the knee. It is estimated that around 1 in 4 with osteoarth ritis of the knee will respond to an intra-articular steroid injec- tion, but identifying t he subgroup who will respond is com- plex. There is a growing literature supporting the ef \201 cacy of steroid into and around soft tissue lesions, although in general this remains an under researched area. Complications Local anesthetic Injection of local anesthetic is relatively safe, but cardia c toxicity limits the dose of anesthetic, which can be injected. Contraindications to arthrocentesis/injections There are no absolute contraindications to a rthrocentesis or joint or soft tissue injections. However, there are some instanced where s pecial precautions are required. \200 Steroid therapy Injection of steroid has a greater number of potential side effects, althou gh many of those reported are rare and by association. Patients should, however, be warned about these prior to the procedure being performed. \200 Bleeding diathesis or anticoagulation. Anticoagulation is not a contraindication to joint o r soft tissue injection, but the INR should be checked prior to the procedure and the proce dure abandoned if the INR is greater than 3. In patients with an INR lower than this, there is an increased risk of haemarthrosis. It is common practice to apply an ice pack after th e procedure to increase vaso- constriction in anticoagulated patients. Prosthetic joints. P rostheses may become infected, but arthrocentesis carries the risk of introduction of infec tion The risk of sepsis following injection is estimated to be between 1 in 15 000 and 1 in 50 0 00 injections. There are no observational studies, and the estimation has been extrapolated from arthroscopic data. Patients who develop a hot, swollen joint after injection should b e investigated and treated as those with a de novo swollen joint (see chapter 16 p. 446). CHAPTER 4 Rheumatological procedures: injection therapy 107 and should only be undertaken by orthopedic surgeons in the sterile environment of theaters . Infection of the overlying skin is a contraindication to arthrocentesis as infection may be introduced into an otherwise sterile joint. No response to previous injection if there h as been no response to a previous injection, the rationale of repeating the procedure shoul d be questioned. While hydrocortisone is easily mixed with local anaes- thetic, methylprednisolone forms a v isible sediment, as does triamcinolone, although this is less marked than with methylpredni solone. The volume of local anesthetic de- pends on the joint to be injected, but normally a volume of 2 \200\2234 ml is suf \201 cient. If a number of joints are to be injected at the same visit, the cumulative dose of local anesthetic should be calculated to ensure toxi city does not occur. The side effects of local anesthetic include allergy, so patients shou ld be observed for 30 min following injection, and especially in high doses as there is a r isk of cardiac toxicity. Ef \201 cacy of different preparations The steroid preparations used have a strong glucoco rticoid action and less of a mineralocorticoid action, therefore optimizing the anti-in \202 ammatory response. The commonest preparations are hydrocortisone, which is relatively short acting, but may have a slightly weaker glucocorticoid action, and methylprednisolone and triamcinolone, which are both longer acting. The longer-acting preparations are used fo r large joint injections, and the shorter acting for small joints and soft tissue lesions. See table 4.1 for suggested doses. Frequency of injections Soft tissue injections can be repeated after an interval of 3 \200 \2236 weeks and joint injections may be repeated after a period of 3 \200\2234 months. In a patient requiring more frequent injections, for example, in a patient with rheumatoid arth ritis, the overall disease management should be reviewed. Table 4.3 Dose and maximum safe volumes of local anesthetic Table 4.1 Suggested doses for steroid injections Drug Strength Maximum safe dose Depomedrone/- methylprednisolone 80 mg Knee 40 mg Ankle Lidocaine 1% 20 ml Wrist 2% 10 ml Elbow Procaine 1% 100 ml Shoulder 2% 50 ml Plantar fasciitis Bupivacaine 0.25% 60 ml Hydrocortisone 25 mg Epicondylitis 0.5% 30 ml 10 \200\22325 mg Carpal tunnel Rest Ef \201 cacy in knee injections is improved in patients who rest for 24 \200\22348 h after injection. It is reasonable to extend this advice to all who receive soft tissue and joint injections, advising avoidance of heavy manual activities for 2 weeks. Tenosynovitis Local anesthetic Local anesthetic is useful both diagnostically and thera- peutically. In c ases where the diagnosis is not clear cut, accurately injected local anesthetic may abolish symp- toms, making a diagnosis more obvious. Local anesthetic is used for the majority of injections as it reduces the initial pain of a post-injection \202 are. Accuracy of injection There ef \201 cacy of a joint injection is greater if the steroid an d local anesthetic are injected directly into the joint, rather than into the periarticular soft tissues. The accuracy is improved if the injection is undertaken under image guidance , and increasingly, USS is used to increase accuracy of injections. Table 4.2 Basic pharmacokinetics of commonly used local anesthetics Drug Onset of action Duration of action Lidocaine 1 \200\2232 min 1 h Procaine 1 min 30 min Bupivacaine 30 min 8 h PROCEDURE 108 Procedure Preparation of equipment \200 The needle and syringes should be disposed of in a sharps bin. The patient should be reasse ssed after the procedure, and the procedure recorded in the medical notes.