WIDESPREAD PAIN IN ADULTS 183 Referral to a sexual health clinic for further detailed investigations if there is a suggestion of recent or recurrent genital infection may help to strengthen the e vidence for a diagnosis of reactive arthritis. Basic laboratory tests in patients with widespread muscle pain/weakness \200 Dipstick uri nalysis: to screen for hematuria or myoglobinuria. \200 CBC and measures of acute-phase r esponse. \200 An endocrine and metabolic screen: urea/electrolytes, creatinine, free thyr oxine and TSH, blood calcium, phosphate and 25-hydroxyvitamin D, LFTs. Elevated CK or aldolase occurs in most cases of PM. ALT, AST, and LDH are nonspeci \201 c markers of muscle damage. Note that speci \201 c muscle isoenzymes of CK and LDH exist and the normal range of all enzymes may vary in different populations. Muscle enzymes may be e levated after nonin \202 ammatory causes of muscle damage, e.g., exercise/trauma. Check for ANA and, if positive, screen for ENAs. Antibodies to certain (cytoplasmic) tRNA synthetases (e.g., Jo-1) are myositis-speci \201 c. All of the procedures just mentioned may reasonably be done in cases where you think muscle pains are due to \201 bromyalgia but want to rule out other pathology. Think of checking for urinary myoglobin in cases where acute widespread muscle pain may be associated with excessive alcohol or ingestion of certain dru gs (cocaine, amphetamines, ecstasy, heroin), exercise, or trauma. Such patients may be at r isk of renal failure. \200 Polymyositis can be a presenting feature of HIV. In HIV-positi ve patients, infections causing muscle disease include TB and microsporidia. Viral myositis may be clinically indistinguishable from PM. Serology may yield diagnostic clues. Electrophysiology and imaging in patients with muscle conditions \200 Electromyographic a bnormalities occur in two-thirds of patients with muscle in \202 ammation. More informatio n is likely if studied in the acute rather than the chronic phase of the illness. In the ac ute phase, denervation and muscle degeneration give rise to \201 brillation potentials in 74% of polymyositis and 33% of dermatomyositis patients. Other features include: low-ampli tude short-duration motor unit and polyphasic potentials. Electromyography is poor at discriminating on-going muscle in \202 ammation in myositis fr om steroid-induced myopathy. There are characteristic MR patterns of abnormality in polymyositis and dermatomyositis. MR can be used to identify potential muscle biopsy sites to avoid false-negative results asso ciated with patchy muscle in \202 ammation. Muscle biopsy \200 Muscle biopsy should be considered in all patients evaluated for polymyositis or dermatomyositis. In polymyositis, in \202 ammatory in \201 ltrates predominate in the endomysial area around muscle \201 bers without perifascicular atrophy. In CHAPTER 3 Patterns of disease presentation 184 Table 3.9 Examples of the prevalence of antinuclear antibodies (ANA) in some diseases using Hep2 cells as substrate Population group Prevalence of ANA Normal population 8% SLE 95% Other autoimmune rheumatic diseases Systemic sclerosis 90% Sj gren \200\231s syndrome 80% Rheumatoid arthritis 60% Polymyositis 40% Polyarteritis nodosa 18% Other diseases Chronic active hepatitis 100% Drug-induced lupus 100% Myasthenia gravis 50% Waldenstrom \200\231s macroglobulinemia 20% Diabetes 25% dermatomyositis, in \202 ammation is more prominent in the perimysial area and around smal l blood vessels and there is typically perifascicular atrophy. Routine tests do not reliably distinguish polymyositis from cases of viral myositis. Some o f the glycogen storage diseases will become apparent from light microscopy of biopsy materi al. Investigations for malignancy Investigations in adults with widespread bony pain should aim to rule out malignancy, particularly myeloma and malignancies from breast, renal and prost ate cancers: \200 Investigations may include: mammography, urine cytology, PSA, renal US, serum and urinary protein electrophoresis. Hypercalcemia may accompany these conditions; check blood calcium, phosphate and albumin (also PTH). Intact PTH should also be checked in suspected cases of osteomalacia (raised due to calcium/vitamin D de \201 ciency) together with 25-hydroxyvitamin D levels (low or low/normal), alkaline phosphatase (high/normal), and 24h urinary calcium (low). Radiographs of affected sites are important. Include a CXR. \200 Bone scintigraphy can id entify sites of neoplasia, Paget \200\231s disease, polyostotic osteoporosis, or osteomalacia (see Plate 17). Although characteristic patterns exist, it is generally not speci \201 c for any condition. WIDESPREAD PAIN IN ADULTS 185 Bone biopsy (maintained undecalci \201 ed by placing sample in 70% alcohol) of affected sites will be diagnostic in some, but not all, cases of osteomalacia, osteoporosis, renal osteodystrophy, malignancy, and Paget \200\231s disease as good samples are hard to obtain. The best samples are obtained from a transiliac biopsy. Bone marrow ca n be aspirated for examination at the same time. CHAPTER 3 Patterns of disease presentation 186 Widespread pain in children and adolescents Background Disease classi \201 cation A workin g party, under the auspices of the International League of Associations for Rheumatology (I LAR) met in 2001 to establish a consen- sus about a unifying classi \201 cation of arthrit is in childhood termed juvenile idiopathic arthritis (JIA). A comparison of old and new cla ssi \201 cation is shown in Table 3.4. For details of each condition, see the relevant dia gnos- tic headings in Chapter 9. \200 Systemic JIA (previously systemic onset JRA) is pro posed to be classi \201 ed as arthritis preceded by or occurring with daily recurring fever of more th an 2 days (documented for greater than 3 days) plus one or more of the following: an evanes cent, non \201 xed, erythematous rash; generalized lymphadenopathy; enlarged liver or sple en; serositis. Persistent oligoarthritis is de \201 ned by the involvement of no more than four joints throughout the disease course. Extended oligoarthritis affects a cumulativ e total of \201 ve joints or more after the \201 rst 6 months of disease. Excluded from these groups are patients with a family history of psoriasis ( \201 rst- or second-degree relative); a positive RF; HLA B27 (male >8 years of age); systemic arthritis. The de \201 nition of psoriatic arthritis has been broadened under the new ILAR classi \201 cation. Enthesitis has a key-classifying role in the group of conditions previously classi \201 ed as SpA. Assess the distribution of the pain Are the pains in a joint distribution? What is their pa ttern? \200 Arthralgias may accompany any infection, although they are generally short li ved. Persistent (>6 weeks) joint pains raise the possibility of many other diseases (see Ta ble 3.10). Poststreptococcal arthralgias are often migratory. Skin overlying joints often appears red in acute rheumatic fever but not in systemic JIA (systemic onset JCA). The presentation of polyarticular JIA (RF/ACPA+ or RF/ACPA \200\223) is often profound, with several weeks \200\231 history of worsening joint stiffness and swelli ng. Stiffness is a prominent associated feature of the joint pain in both (RF/ ACPA+) and (RF/ACPA \200\223) polyarticular JIA. Taking a history Are the pains due to myalgias or myositis? The differential diagnosis is w ide (see Table 3.11): \200 Acute viral myositis is distinguished from chronic myositis by its localization to calf muscles, severe pain, and its resolution within 4 weeks. WIDESPREAD PAIN IN CHILDREN AND ADOLESCENTS 187 Table 3.10 The differential diagnosis of (RF \200\223) JIA Infection (multiple sites in immunode \201 ciency) Staphylococcus septic arthritis Haemophilus in \202 uenzae septic arthritis Reactive to an infectious agent Parvovirus B19, hepatitis, rubella, rubella vaccination Post-streptococcal, rheumatic fever Autoimmune connective tissue disorders SLE MCTD, overlap syndromes Poly/dermatomyositis Systemic vasculitis syndromes Kawasaki disease (young child, high fever, desquamating extremity rash) Polyarteritis nodosa Granulomatosis with polyangiitis (Wegener \200\231s) HSP, Beh et \200\231s disease Sarcoid arthritis (polyarthritis, rash, uveitis) Hematological disorders Sickle cell disease Constitutional bleeding disorders Acute leukemia (bone and joint pain) Other causes Chronic recurrent multifocal osteomyelitis Diabetic cheiroarthropathy Familial Mediterranean fever Chronic muscle weakness suggests an autoimmune connective tissue disease such as juvenile d ermatomyositis. Myalgias and muscle cramps occur in hypothyroidism, uremia, and electrolyte imbalance. \200 Myalgias are common in pediatric SLE, but myopathy occurs rarely (10%). Episodic cramping or muscle pain related to exercise in early childhood might re \202 ect muscular dystrophy, congenital myopathy, myotonic disorders, o r genetic defects in glycogen or glucose metabolism. A pain syndrome (e.g., \201 bromyalgia) is a diagnosis of exclusion. Enthesitis (ERA) should be carefully excluded. Is there bone pain? Do the pains represent bone pain \200\224persistent, deep-seated pains which change little with posture or movement? \200 Night-time pain is typical of bony inv olvement in malignancy or osteomyelitis. Acute lymphoblastic leukemia, lymphoma, and neuroblastoma are the most co mmon malignant lesions. Achy \200\234bony \200\235 pain around joints may be due to enthesitis. Patients with ERA/SpA can present with enthesitis alone. Migratory bone pains are typical in multifocal osteomyelitis. CHAPTER 3 Patterns of disease presentation 188 Is the child with arthritis systemically unwell? \200 Malignancy should be ruled out and vasculitis and autoimmune connective tissue diseases considered in all children with persistent polyarthritis or wide spread pains who have systemic symptoms. \200 Fever is nonspeci \201 c but essential to making a diagnosis of systemic JIA (see Figure 3.3), which is associated with spiking fever s, chills, and sweats. Anorexia and weight loss are common. Vasculitis (see Chapter 15) and FMF (see Chapter 18) should be considered in appropriate patients. There may be several months between the onset of systemic features and the arthritis of systemic JIA. Serositis is typical in systemic JIA but also occurs in SLE. Table 3.11 Classi \201 cation of childhood disorders characterized by myalgias and muscle weakness Muscular dystrophies X-linked, e.g., Duchenne Autosomal dominant, e.g., fascioscapulohumeral Autosomal recessive: limb girdle Congenital myopathies e.g., myopathic arthrogryposis Myotonic dystrophy Metabolic disorders Glycogen storage disease, e.g., acid maltase/ phosphorylase/phosphofructokinase de \201 ci ency Familial periodic paralyzes Due to endocrinopathies, e.g., Addison \200\231s disease, Cushing \200\231s disease In \202 ammatory diseases Postinfectious, e.g., viruses \200\224in \202 uenza B, coxsackie B, echo, polio Autoimmune, e.g., juvenile RA, dermatomyositis, SLE Genetic abnormalities Osteogenesis imperfecta Ehlers \200\223Danlos Mucopolysaccharidoses Trauma Physical, e.g., rhabdomyolysis Toxic, e.g., snakebite Drugs, e.g., steroids, hydroxychloroquine, diuretics Neurogenic atrophies Spinal muscular and anterior horn cell dysfunction Peripheral nerve, e.g., peroneal muscular atrophy Neuromuscular, e.g., congenital myasthenia WIDESPREAD PAIN IN CHILDREN AND ADOLESCENTS 189 42 41 40 C e r u t a r e p m e T 39 38 37 36 35 0 8 16 24 8 16 24 8 16 24 8 16 24 8 16 24 8 16 24 8 16 24 4 Day 1 2 3 5 6 7 Fig. 3.3 Double-daily fever spikes with rapid return to below 37 C in systemic JIA (system ic-onset JRA) In children <1 year, fever and arthralgias raise the possibility of chronic infantile neuro logical cutaneous and articular (CINCA) syndrome (see Chapter 9) and hyperimmunoglobulin D syndrome. A catastrophic illness can occur in children with systemic JIA. It is termed macrophage-activation or hematophagocytic syndrome and is characterized by cytopenia s, hepatic dysfunction, encephalopathy, and disseminated intravascular coagulation with ble eding. A history of recurrent infections and arthritis may suggest immunode \201 ciency. The most common is X-linked humoral de \201 ciency. Is there a rash? Does the child have a rash or did one precede the onset of pains? \200 R ashes raise the possibility of preceding infection: EBV, rubella, and adenovirus are common and are associated with myalgias, arthralgias, and fever. The rash of systemic JIA is a salmon-pink macular rash. Lesions may either persist or come and go and may exhibit K ebner phenomenon \200\224the exaggeration of the rash at sites of trauma. UV skin sensitivity may indicate SLE or dermatomyositis. \200 Check for a vasculitic rash (e.g., HSP, cutaneous PAN). Systemic vasculitis can be associated with recurrent fevers an d joint pains. Are there ophthalmic symptoms? Eye symptoms are an important indicator of underlying autoim munity in the context of persistent joint or muscle pains: \200 Uveitis is associated wit h most forms of JIA (particularly in association with ANA), but also may indicate an ERA/SpA (uveitis = pain/ discomfort, blurring of vision , photophobia and a \200\234red eye \200\235). CHAPTER 3 Patterns of disease presentation 190 Impairment of visual \201 elds suggests a retinal abnormality \200\224a typical manifestation in juvenile dermatomyositis (due to occlusive vasculopathy). The challenge is that most uveitis is generally asymptomatic in children with JIA. Screenin g is imperative to identify those with active disease. Examination Full medical examination A full medical examination is essential: \200 Pharyn geal erythema is nonspeci \201 c and swabs should be cultured for streptococci. Sterile ph aryngitis is a known feature of systemic JIA. Lymphadenopathy is common but nonspeci \201 c. \200 For skin examination in detail see t he preceding sections under Widespread Pain in Children and Adolescents. UV sensitivity occurs in DM and SLE; healing p soriasis may mimic Gottron \200\231s lesions; calcinosis and pretibial hypopigmentation are signs of DM. The cardiovascular examination is important. Pericarditis is common in systemic and other f orms of JIA but is infrequently detected clinically. Myocarditis and heart failure also occ ur (rarely) in systemic JIA. Persistent tachycardia without anemia/fever raises the possibi lity of myocarditis. Cardiac conduction defects are common in juvenile DM. A variety of cardiac conditions occur in (RF/ACPA+) JIA including aortic valve insuf \201 ciency. The latter also occurs in ERA/SpA (8 \200\22330%). \200 Respiratory examination may be abnormal if the arthralgias/arthritis are associated with respiratory tract infection; however, \201 xed crackles may indicate \201 brosis (e.g., (RF+) JIA, PM) and a simultanous reduction in expansion, breath sounds , and vocal fremitus suggests pleural effusion (e.g., (RF+) JIA). Bedside eye examination may be unrevealing even in those with ophthalmic symptoms. Thrombosis of dilated blood vessels at the margin of the upper lid is characteristic of dermatomyositis and polymyositis. Dry eyes are a common complaint, and ma y be the result of medication side effects; dry eyes are also found in association with a n umber of rheumatic diseases. As with all chronic conditions of childhood, growth and maturation (skeletal, endocrine/pub ertal, and psychological) assessments should be considered at regular intervals. Musculoskeletal examination \200\224general principles \200 Synovitis of a joint is chara cterized by soft-tissue swelling, effusion, and a reduced range of joint movement. Enthesitis may not be accompanied by an effusion; it can appear alone at bony insertions of ligaments/tendons with joint stiffness but without swelling. Tendonitis can be dif \201 cult to distinguish from synovitis. Its diagnosis requires a precise knowledge of anatomy. The in \202 amed tendon may be more painful on ac tive range of motion exercises. If the condition is chronic, an assessment of limb growth should be done, e.g., measuring leg length discrepancy (see Plate 18). WIDESPREAD PAIN IN CHILDREN AND ADOLESCENTS 191 Musculoskeletal examination \200\224patterns of joint, tendon, and enthesis involvement A f ull examination should be undertaken: \200 Ligament/tendon insertion tenderness, not nece ssarily associated with swelling, may denote enthesitis. Enthesitis, which is probably more common (or at least more commonly recognized in lower limbs) raises the possibility of ERA /SpA. Almost any joint can be involved, including those in the cervical spine. Hip joint involvement is almost always symmetric. There is no consistent pattern of joint or tendon involvement that distinguishes polyarticu lar (RF+) JIA from the majority of conditions associated with, or characterized by, polyart icular (RF \200\223) JIA. Subsets of polyarticular (RF \200\223) arthritis have been suggested on the basis of featur es such as \200\234painful \200\235 or \200\234dry \200\235 synovitis, stiffness, and oth er laboratory and genetic indices. Muscle tenderness is not speci \201 c. If con \201 ned to the calves, consider viral myos itis. Weakness can accompany metabolic and endocrine myopathies and is not speci \201 c fo r in \202 ammatory myopathy. Muscle weakness at rest may be present in children with severe forms of inherited metabolic muscle diseases. Often weakness only becomes apparent after exercise in these conditions ( see Table 3.12). Laboratory tests \200 Laboratory abnormalities are nonspeci \201 c in polyarticular (RF \200\223) JIA. \200 Because RF may appear in association with infections, ILAR criteria p ropose that signi \201 cant titers of RF should be demonstrated on two occasions at least 3 months apart to make a diagnosis of polyarticular (RF+) JIA. ACPA, on the other hand, are sensitive and speci \201 c for a diagnosis of polyarticular JIA. A range of laboratory investigations is suggested when considering a diagnosis of systemic JIA (see Table 3.13). Lymphopenia is a hallmark of DM and SLE, and is not a feature of in \202 ammatory arthritis. Neutrophilia and thrombocytosis are invariably present and can be marked in systemic JIA whereas leukopenia and thrombocytopenia are uncommon. Urinalysis is important in all children with widespread pains and may detect blood or hemog lobinuria in some muscle diseases (actually is myoglobin). Protein and blood may be a sign of underlying kidney in \202 ammation in connective tissue diseases. Conventional acute phase markers can be normal in PM/DM. A sensitive indicator (though nons peci \201 c) of active disease is von Willebrand factor. A raised CK, ALT/AST, or aldolase is a sensitive but not speci \201 c sign of autoimmune myositis. A positive ANA is found in association with many autoimmune connective tissue diseases and some JIA subsets. ANA (speckled) is positive in 60 \200\2237 0% of children with polymyositis and dermatomyositis. \200 Additional initial investigati ons in those suspected of having myopathic pains include bone biochemistry and TFTs. CHAPTER 3 Patterns of disease presentation 192 Imaging tests: radiographs \200 Employ specialist pediatric radiologists and technicians if possible. \200 Proper X-ray beam coning, high-speed intensifying screens, gonadal shielding, and digital radiography all reduce radiation dose. \200 Soft tissue swelling a nd joint-space widening are important, but nonspeci \201 c, signs of early arthritis in young children. The most easily recognized sign of early polyarthritis in an older child will be periarticular osteopenia. At joints also look for joint space narrowing, erosions, growth abnormalities, subluxation, and ankylosis. All occur at multiple joints in systemic JIA and polyarticular JIA. In children with abnormalities in stature/skeletal morphology look for diffuse but subtle changes in bone quality and epiphyses. Destruction of bone cortex at sites of pain in patients with myalgias, arthralgias, or polyarthritis may suggest malignancy. Table 3.12 Characteristics of rare inherited causes of muscle pain and/or weakness Condition Musculoskeletal features Other features Acute rigidity and subsequent rhabdomyolysis Acute \200\224fever. Hyperkalemia Malignant hyperthermia (muscle sensitivity to severe physical or metabolic stress) McArdle \200\231s disease (myophosphorylase de \201 ciency) Painful (temporary) muscle contractures triggered by exercise Autosomal recessive. Genotypic and phenotypic heterogeneity Tauri \200\231s disease (phosphofructokinase de \201 ciency) Similar to McArdle \200\231s Hemolytic anemia (reticulocytosis) Von Gierke \200\231s disease (glucose 6 phosphatase de \201 ciency) Skeletal myopathy Hepatomegaly. Growth retardation. Hypoglycemia. Lactic acidosis Pompe \200\231s disease (acid maltase de \201 ciency) Severe skeletal muscle weakness and cardiomyopathy Death in \201 rst year Cori \200\223Forbes disease (debrancher enzyme de \201 ciency) Variation from severe childhood myopathic to symptomless adult forms Mitochondrial myopathies Severely limited exercise capacity Dyspnea. Lactic acidosis WIDESPREAD PAIN IN CHILDREN AND ADOLESCENTS 193 Table 3.13 Useful tests in investigating suspected systemic JIA In all patients: CBC, ESR, CRP Renal and liver biochemistry, serum albumin Serum immunoglobulins Clotting screen Blood cultures ECG, CXR, abdominal/pelvic US ANA Bone marrow aspiration and biopsy Ocular slit-lamp examination Joint aspirate (single joint) Radiographs of selected affected joints In selected patients: Muscle enzymes (CK, ALT/AST, and aldolase) RF/ACPA Isotope bone/gallium scan Upper GI series/small bowel follow-through Tissue biopsies Viral serology \200\224parvovirus, adenovirus, others Echocardiogram ASO/antihyaluronidase antibodies Urinary homovanillic/vanillylmandelic acid Serum IgD Imaging: US, skeletal MR, and bone scan \200 The role of US is expanding. It is noninvasi ve, nonionizing, can be done at the bedside, and is generally accepted well by children. With US, cartilaginous forms of bones can be visualized. This is especially advantageous in the hip where femoral head position and abnormal movement can be seen in young children. US is very useful for identifying effusions, notably in the hip, and for discriminating effusion from synovial thickening. Bone scan provides critical information in musculoskeletal pain when radiographs are unreve aling. Though of less use when joints are involved, bone scan should be considered when pai n originates in bone or infection is a possibility. CT is a reliable way of documenting sacroiliac disease in children suspected of having ERA (SpA). CHAPTER 3 Patterns of disease presentation 194 MR has become the imaging modality of choice, especially when the diagnosis of JIA is not straightforward. It is more sensitive than radiographs for dete cting soft-tissue and most bone lesions. MR is more sensitive than radiographs for detecting changes in joints associated with chronic arthritis. MR should provide diagnostic information if there is dou bt about the presence of arthritis in a joint after clinical examination and radiographs. The discrimination of synovitis and enthesitis by MR may have implications for the diagnosi s of ERA (SpA) compared with JIA. Investigations of muscle pains \200 EMG patterns of abnormality occur in muscular dystrop hy, myasthenia gravis, and autoimmune myositis but each is not speci \201 c. Evidence of an in \202 ammatory myopathy on EMG is not speci \201 c to juvenile dermatomyositis and may be due to a myositis-component of another autoimmune conne ctive tissue disease. MR can con \201 rm myositis and reveal potential sites of biopsy in what can be a patchy process. 195 Chapter 4 The spectrum of presentation of rheumatic disease Skin disorders and rheumatic disease 196 Skin vasculitis in adults 202 Skin vasculitis in c hildren and adolescents 206 Cardiac manifestations 210 Pulmonary manifestations 214 Renal m anifestations 216 Endocrine manifestations 220 Gut and hepatobiliary manifestations 224 Mal ignancy 230 CHAPTER 4 The spectrum of presentation 196 Skin disorders and rheumatic disease The importance of examining the skin \200 The skin i s the most accessible organ to examine. \200 Pattern recognition of skin symptoms and les ions is valuable in aiding diagnosis (e.g., acute or chronic sarcoid) and prognosis of rheu matic diseases (e.g., nodules and vasculitis in RA). Musculoskeletal abnormalities may be mirrored by skin abnormalities (e.g., joint hypermobil ity and skin laxity with bruising, scarring, and striae). Some antirheumatic drugs produce highly speci \201 c and potentially serious cutaneous rea ctions that require prompt diagnosis and management. Regional abnormalities The scalp Scalp symptoms and lesions may be subtle: \200 Scalp ten derness and the description of scalp \200\234lumps \200\235 (due to temporal artery aneurysms) are recognized in giant cell arteritis. C2 root/occipital neuropathy (e.g., in RA) or shingles may be associated with dysesthesias over the scalp and occipital neuralgia. Alopecia may be localized (areata) or diffuse (e.g., in SLE or iron de \201 ciency). Scarring alopecia is typical of discoid lupus. Scalp psoriasis may be evident along the hairline \200 A \200\234salt and pepper \200 \235 pattern of hyperpigmentation and hypopigmentation may be seen in scleroderma. Face and ears Face and ears are in sun-exposed areas. Consider UV skin sensitivity: \200 A variety of patterns of SLE-associated, UV-sensitive rashes may occur. The rash is often d iffuse. Shaded areas (e.g., nasolabial folds) may not be affected (see Chapter 10). As in SLE, rosacea can present with an erythematosus facial rash, but does not spare the na solabial folds. Distinction is sometimes dif \201 cult without biopsy. Periorbital edema occurs in dermatomyositis, angioedema (which may be a presenting feature of SLE), and in nephrotic syndrome. Heliotrope rash refers to violaceous edema/erythema of the eyelids in dermatomyositis (see Chapter 14). The cutaneous in \201 ltration of chronic sarcoid (lupus pernio) (see Chapter 18) across the nose and cheeks may be overt (papular) but also may be quite subtle (see Plate 19). Saddle nose deformity/nasal cartilage destruction has a number of causes: granulomatosis wi th polyangiitis (Wegener \200\231s) (see Chapter 15), relapsing polychondritis (see Chapter 18), sarcoidosis, hereditary connective tissue disease (e.g., Stickler \200\231s syndrome see Chapter 16), and lethal midline granuloma. Nasal septal and palatal perforation can als o occur in the setting of cocaine use. Ear deformities ( \200\234cauli \202 ower ear \200\235) may be associated with relapsing polychondritis. SKIN DISORDERS AND RHEUMATIC DISEASE 197 Purpuric lesions on the ears (in the absent of overt auricular deformity) may be due to levamisole, which is a common adulterant in cocaine. The pinna is a common site for gouty tophi and discoid lupus. \200 Oral aphthous ulcers a re common. Oral ulceration may follow disease activity (e.g., in SLE or granulomatosis with polyangiitis (Wegener \200\231s granulomatosis)) Ulcers in reactive arthritis are typicall y painless. Oral aphthous ulcers are frequently idiopathic, and not associated with systemi c disease. Large punched-out and numerous tongue and buccal ulcers that scar are a hallmark of Beh et \200\231s disease (see Chapter 18). They may remain for several weeks. Strawberry erythema of the tongue and lips should not be missed in children. It may denote self-limiting streptococcal infections but may also herald the desquamating palmar (and sol e) rash of Kawasaki disease (see Chapter 15). Strawberry (i.e., erythematous/swollen) gums may be a sign of granulomatosis with polyangii tis (Wegener \200\231s granulomatosis). \200 Lacy white streaks on the buccal mucosa sugg est lichen planus. \200 Lipid skin deposits around the eye occur in hyperlipidemia and multicentric reticulohistiocytosis Hands and nails Hands and nails should be examined closely: \200 A photosensitive eruptio n spares the \201 nger webs and palms. \200 Erythema on the back of the \201 ngers ma y help distinguish dermatomyositis from SLE. In patients with Raynaud \200\231s phenomenon (RP), \201 nger ulceration, \201 nger pul p atrophy (with smooth tapering of the \201 nger tips), induration, and tethering of the skin indicates scleroderma (see Chapter 13). Unlike normal skin, the skin of scleroderma do es not form \201 ne wrinkles when pinched. Onycholysis, pitting, salmon patches, and subungual hyperkeratosis are typical of psoriasis (see Chapter 8). Subungual splinter hemorrhages may be associated with trauma, infective endocarditis, systemic vasculitis, or thromboangiitis obliterans. Nailfold capillaries can be examined with an ophthalmoscope at 40 diopters after applying a drop of oil (or surgical lubricant) to the cuticle. Enlarged (dilated) capillary loops and capillary \200\234dropout \200\235 suggests an underlying autoimmune connective tissue di sease, particularly scleroderma and dermatomyositis. Types of eruption Macular rashes Macular rashes are \202 at (nonpalpable) areas of altere d skin color. Papules are lumps <1 cm in diameter: \200 Maculopapular rashes are typical of viral infections. \200 A short-lived, pinkish ( \200\234salmon-colored \200\235), macu lopapular eruption occurs on the trunk and limbs in Still \200\231s disease. It is often prominent in CHAPTER 4 The spectrum of presentation 198 the late afternoon, and coincides with temperature spikes. If scratched, the rash may blanc h ( \200\234K ebner phenomenon \200\235). Erythema that enlarges to form erythematosus patches with pale centers suggests rheumatic f ever ( \200\234erythema marginatum \200\235). A \200\234bulls-eye \200\235 erythematosus lesion around a tick bite may be the erythema migrans of Lyme disease. Maculopapular eruptions can occur from NSAIDs, gold, D-penicillamine, sulfasalazine, azathioprine hypersensitivity, and le \202 unomide (see Ch apter 5). Pustules and blisters Blisters may be vesicles (<0.5 cm diameter) or bullae (>0.5 cm diamet er): \200 The most common pustular rash is due to folliculitis. \200 Pustules con \201 ned to the hands and feet suggest reactive arthritis, although local forms of psoriasis may be indistinguishable. Psoriasis can also occur as \200\234raindrop \200\235 erythematous lesions, also known as guttate lesions. Generalized pustular rashes can occur in vasculitis, the neutrophilic dermatoses, intestina l bypass syndromes, Beh et \200\231s disease, and gonococcal bacteremia. Bullous eruptions may be due to SLE, drug reactions, pemphigus and pemphigoid. Plaques Plaques are slightly raised, circumscribed areas of skin, often disc shaped: \200 Plaques are the hallmark of psoriasis. Skin may be scaly and \202 ake off easily. Lesions are often red. Psoriatic plaques can occur anywhere on the skin, but typical sites are over the extensor s urfaces of the joints, in the intergluteal cleft, and the umbilicus. Scaling may be a feature of discoid lupus; scaling tends to occur at the periphery of the lesion. Vascular lesions Bleeding into the skin that does not blanch is called purpura. It may some - times be palpable. Telangiectasias are dilated small vascular lesions that blanch on pres sure: \200 Nonpalpable purpura may be due to thrombocytopenia, platelet dysfunction, trauma ( capillary/skin fragility, e.g., chronic steroid use), hemophilia, a nticoagulation, and hereditary connective tissue diseases (e.g., Ehlers-Danlos \200\224see Chapter 16). Palpable purpura suggests vasculitis, including drug-induced (see Chapter 15). Widespread telangiectasias occur in limited cutaneous scleroderma (see Chapter 13), hereditary hemorrhagic telangiectasia, and dermatomyositis. Ulcers and ulcerating rashes Ulcers are de \201 ned as a loss or defect of dermis and epid ermis produced by sloughing of necrotic tissue: SKIN DISORDERS AND RHEUMATIC DISEASE 199 Cutaneous polyarteritis nodosa may cause painful ulcerating lesions in the lower extremitie s, as can other forms of systemic vasculitis that affect the medium-sized vessels. Cutaneous ulceration may have more than one cause in autoimmune diseases. For example, vasc ulitis, venous stasis in an immobile patient, and ulceration over nodules or pressure point s may all contribute to the same set of lesions. Trauma may be an important cause of cutane ous ulcers in a patient who is already predisposed towards forming these lesions. A painful, indurated, expanding, plum-colored plaque or acneiform pustule that then ulcerates suggests pyoderma gangrenosum. The ulcer has irregular, bluish margins. Neurotropic ulcers are a classic sequelae of diabetes, but they can also occur in associati on with mononeuritis multiplex (from vasculitis) and other rheumatic diseases. Severe widespread ulceration developing rapidly in a child may suggest dermatomyositis. Vasculitic ulcers in the context of livedo reticularis and antibodies to phospholipids (e.g., cardiolipin) may be indicative of the antiphospholipid antibody syn drome (APS) (see Chapter 11). Textural abnormalities Abnormalities of the texture of the skin may be dif \201 cult to di scern. Atrophy and thinning, laxity, thickening, and induration may all be associ- ated wit h disease. \200 Generalized skin atrophy and thinning is an age-related process, but this can be accelerated by chronic steroid use; heritable diseases of connective tissue should also be considered. Skin laxity can best be demonstrated over elbow and knee extensor surfaces. Generalized laxity of connective tissue may result in varicose veins and internal organ prolapse. True acral and digital puf \201 ness in a patient with Raynaud \200\231s is suggestive of scleroderma. Skin thickening has a variety of causes (see below). Scleroderma and scleroder ma-like skin may be localized, limited, or diffuse \200\224this distinction is important (s ee Table 4.1). Diagnostic issues in patients with skin thickening \200 Raynaud \200\231s phenomenon (RP) invariably precedes the onset of systemic sclerosis (scleroderma), but is not a characteri stic of morphea, linear scleroderma, or scleroderma mimics. In patients with RP, abnormal nailfold capillaries on capillaroscopy may indicate the presence of scleroderma or \200\234prescleroderma \200\235 (see Plate 4). The speci \201 cities of autoantibodies are often predictive of the scleroderma subtype. In patients with RP, the ANA has predictive value for identifying pati ents who may progress to scleroderma; anticentromere antibodies are associated with limited cutaneous scleroderma; anti-topoisomerase I (SCL-70) and anti-RNA polymerase III antibodie s are linked with progression to diffuse cutaneous scleroderma. CHAPTER 4 The spectrum of presentation 200 Patients with diffuse cutaneous scleroderma have a preponderance of visceral organ involvement in the \201 rst 5 years of disease; screening investigation s should include pulmonary function tests, an echocardiogram, and a high-resolution CT of t he chest to screen for pulmonary hypertension and pulmonary \201 brosis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome, and is associated with hemat ologic malignancies. Clinically, eosinophilic fasciitis is associated with skin that takes on the appearance of an orange peel ( peau d \200\231orange ). Linear scleroderma in children can produce lifelong deformities because limbs to develop correct length and bulk. Scleroderma-like syndromes may occur secondarily to exposure to some industrial chemicals: vinyl chloride, chlorinated organic solvents, and silicon and ep oxy resins. SKIN DISORDERS AND RHEUMATIC DISEASE 201 Table 4.1 Pattern recognition in patients with skin thickening Classi \201 cation Skin features Early small skin areas affected (itchy). Progression to hidebound skin, typically on trunk (areola spared) and legs. Lesions become waxy and hypo/ hyperpigmented guttate (small <10 m m) papules usually on neck and anterior chest Morphea may be localized (guttate) or generalized Linear scleroderma Linear bandlike pattern often in dermatomal distribution. Atrophy of muscles is common. Fix ed joint deformities and growth abnormalities can occur \200\234Coup de saber \200\235 Linear scleroderma on the face/scalp can be depressed; ivory in appearance. Hemiatrophy can occur Systemic sclerosis (early) Early morning \200\234puf \201 ness \200\235 in hands and feet, facial \200\234tightness . \200\235 Nonpitting edema of intact dermal and epidermal appendages. High degree of suspi cion needed Systemic sclerosis (classic) Firm, taut, hidebound skin proximal to MCP joints. Skin may be coarse, pigmented, and dry. Epidermal thinning, loss of hair, and sweating can occur. Telangiectasias and skin calcinos is become obvious. Skin creases disappear. Such change proximal to elbows or knees in the l imbs or below the clavicles (in those with face and neck involvement) classi \201 es disea se as diffuse as opposed to limited systemic sclerosis Systemic sclerosis (late) 2 \200\22315 years after onset of classical phase, skin softens but pigmentation changes re main. Skin becomes atrophic and can ulcerate Eosinophilic fasciitis Phases: early \200\224pitting edema; progressive \200\224 peau d \200\231orange; late \200 \224induration ( \200\234woody feel \200\235) with venous guttering when limb elevated. Arm s and legs most commonly affected but \201 ngers mainly spared. Synovitis and low-grade m yositis may occur. Eosinophilia is usually striking but not always present Lipodermatosclerosis Fibrotic induration of lower legs associated with venous stasis ( \200\234champagne-bottle legs \200\235) Diabetes Waxy thickening of extremities. Insidious progression. Joints of the hands become stiff, th e tendons can thicken. Skin changes proximal to wrist and on the face very unlikely but sti ffening of elbow and shoulder joints not uncommon Dependent lymphedema Feet/ankles/lower legs. Often pitting. Chronic presence may give hyperkeratosis. Main cause s: R- or L-sided heart failure, renal failure, nephrotic syndrome, and low-protein states CHAPTER 4 The spectrum of presentation 202 Skin vasculitis in adults Background There are a variety of ways in which systemic vasculit is may present, including fever of unknown origin, organ infarction, gastrointestinal bleed - ing, and high acute phase reactants in a generally unwell patient. However, a vasculitic skin rash is one of the most common presenting features of systemic vasculitis, and can be an important diagnostic clue. When to consider a diagnosis of vasculitis (see also Chapters 15 and 22) \200 Systemic va sculitis is rare. Overall, the annual incidence is about 40 per million. Cutaneous vasculitis, however, is not rare; it can follow viral or bacterial illness, can b e triggered by drugs, and is associated with malignancy. Biopsy generally demonstrates degranulation of neutrophils ( \200\234leukocytoclasis \200 \235) and evidence of vessel destruction. The list of causes is long (see Table 4.2); however, in about 50% of