40.1 Rheumatology and Dermatology: Approach to Arthritis, Osteoarthritis, Rheumatoid Arthritis, Gout, Spondyloarthritis, SLE and Other Connective Tissue Diseases, Vasculitis and Myalgias, Bone Tumors, Common Skin Lesions, Skin Infections and Infestations, Eczema, Psoriasis, Severe Drug Eruptions and Skin Signs of Systemic Disease

Why this area matters

Gout is common in Filipino men (linked to seafood, organ meats, beer and sugary drinks), and SLE in young Filipino women often presents with lupus nephritis. Scabies, tinea and impetigo are among the most common skin problems in crowded homes and schools, and severe drug eruptions in Asians are partly genetic. The PLE asks you to classify joint pain, interpret the joint fluid and autoantibodies, and recognize dangerous rashes.

Approach to joint and muscle pain

• Inflammatory or mechanical?
  • inflammatory: morning stiffness over 1 hour, swelling, warmth, and improvement with activity (RA, spondyloarthritis, crystal arthritis);
  • mechanical: pain worse with use, stiffness under 30 minutes (osteoarthritis).
• Number of joints:
  • monoarthritis: septic arthritis, gout, pseudogout and trauma. Aspirate the joint for cell count, Gram stain, culture and crystals;
  • oligoarthritis (2 to 4 joints): spondyloarthritis and reactive arthritis;
  • polyarthritis: RA, SLE, viral arthritis (chikungunya, parvovirus, hepatitis B) and psoriatic arthritis.
• Osteoarthritis:
  • degeneration of cartilage in knees, hips, the hands (DIP joints: Heberden nodes; PIP joints: Bouchard nodes) and spine;
  • X-ray shows joint space narrowing, osteophytes, subchondral sclerosis and cysts;
  • treated with weight loss, exercise and physiotherapy, topical then oral NSAIDs, intra-articular steroids, and joint replacement for end-stage disease.
• Myalgias:
  • viral illness, leptospirosis (calf tenderness), dengue and influenza;
  • statin myopathy (check CK);
  • hypothyroidism;
  • polymyalgia rheumatica;
  • inflammatory myopathies;
  • fibromyalgia: widespread pain, fatigue and poor sleep with normal tests, treated with exercise, sleep care and duloxetine or amitriptyline.

Autoimmune & Rheumatologic Disorders

Rheumatoid Arthritis (RA)

Symmetric, destructive inflammatory polyarthritis driven by synovial proliferation (pannus formation), bone erosion, and cartilage degradation.

• Clinical Presentation: Pain, warmth, and swelling symmetrically involving small joints of the hands and feet: Metacarpophalangeal (MCP), Proximal Interphalangeal (PIP), and wrist joints. Characterized by prolonged morning stiffness lasting $> 1\text{ hour}$ that improves with joint movement. Spares the distal interphalangeal (DIP) joints and thoracolumbar spine (cervical spine atlantoaxial subluxation is a serious exception).
• Autoantibody Biomarkers:
  • Anti-Cyclic Citrullinated Peptide (Anti-CCP / ACPA): Highly specific ($> 95-98\%$); predicts progressive, erosive joint destruction.
  • Rheumatoid Factor (RF): IgM autoantibody against the Fc portion of human IgG. Sensitive ($70-80\%$) but non-specific (seen in hepatitis C, SBE, SLE, Sjogren's).
• Pharmacotherapy: Early initiation of Disease-Modifying Antirheumatic Drugs (DMARDs) is mandatory to prevent irreversible joint deformity. Methotrexate (MTX) is the first-line anchor conventional DMARD (dihydrofolate reductase inhibitor; co-prescribe folic acid $1-5\text{ mg/day}$; monitor for hepatotoxicity, cytopenias, and pneumonitis; strictly contraindicated in pregnancy). Biologic DMARDs (TNF-alpha inhibitors: Infliximab, Adalimumab, Etanercept) are indicated for refractory disease; screening for latent tuberculosis (IGRA/PPD) and hepatitis B is mandatory before initiation to prevent fulminant reactivation.

Systemic Lupus Erythematosus (SLE)

Multisystem autoimmune disorder mediated by autoantibody production and immune complex deposition (Types II and III hypersensitivity), predominantly affecting young women of childbearing age.

• EULAR/ACR 2019 Classification: Entry criterion is an Antinuclear Antibody (ANA) titer $\ge 1:80$. Additive weighted domains include constitutional fever; cutaneous (malar rash, discoid lupus, oral ulcers, non-scarring alopecia); arthritis; serositis (pericarditis, pleuritis); hematologic (autoimmune hemolytic anemia, leukopenia $< 4,000/\mu\text{L}$, thrombocytopenia $< 100,000/\mu\text{L}$); neurologic (seizures, psychosis); and renal (proteinuria $> 0.5\text{ g/24h}$ or biopsy-proven lupus nephritis).
• Diagnostic Autoantibody Profiles:
  • Antinuclear Antibody (ANA): Most sensitive ($> 95\%$); ideal screening test; low specificity.
  • Anti-double-stranded DNA (Anti-dsDNA): Highly specific ($> 95\%$); titers fluctuate with disease activity and correlate strongly with lupus nephritis and complement consumption (low serum C3 and C4).
  • Anti-Smith (Anti-Sm): Highest specificity for SLE; does not correlate with disease activity.
  • Anti-Ro/SSA & Anti-La/SSB: Associated with subacute cutaneous lupus, secondary Sjögren syndrome, and neonatal lupus complicated by congenital complete heart block.
• Management: Hydroxychloroquine is recommended for all SLE patients (reduces disease flares, organ accrual, and thrombosis; requires baseline and annual retinal screening after 5 years for chloroquine maculopathy). Systemic glucocorticoids for acute disease flares; immunosuppressive therapy (Mycophenolate Mofetil or IV Cyclophosphamide) is standard for proliferative lupus nephritis (Class III/IV).

Crystalline Arthropathies: Gout versus Pseudogout

More on gout and RA:

• Gout triggers: alcohol (especially beer), seafood and red meat, fructose drinks, dehydration, thiazide and loop diuretics, low-dose aspirin and starting urate-lowering therapy.
• Indications for urate-lowering therapy: tophi, 2 or more flares a year, radiographic damage, and (conditionally) kidney stones or CKD.
• Starting allopurinol:
  • start low (50 to 100 mg a day, lower in CKD) and titrate to a urate target below 6 mg/dL;
  • give colchicine or an NSAID as flare prophylaxis for 3 to 6 months;
  • do not stop ULT during a flare.
• RA extra-articular features: rheumatoid nodules, interstitial lung disease, scleritis, Felty syndrome (RA, splenomegaly, neutropenia), vasculitis and atlantoaxial subluxation (check before intubation). Risk of coronary disease is increased.

Spondyloarthritis

• Ankylosing spondylitis:
  • inflammatory back pain in men under 40: insidious, night pain, morning stiffness that improves with exercise;
  • sacroiliitis on X-ray or MRI, later a "bamboo spine";
  • HLA-B27, anterior uveitis and enthesitis (Achilles tendon);
  • treated with NSAIDs and exercise, then TNF or IL-17 inhibitors.
• Reactive arthritis: asymmetric oligoarthritis after urethritis (chlamydia) or dysentery (Shigella, Salmonella, Campylobacter), with conjunctivitis and urethritis.
• Psoriatic arthritis: DIP involvement, dactylitis ("sausage digits"), nail pitting and arthritis mutilans.

Other connective tissue diseases and vasculitis

• Systemic sclerosis:
  • Raynaud phenomenon, skin thickening (sclerodactyly), digital ulcers, GERD and dysmotility, interstitial lung disease and pulmonary hypertension;
  • limited form (CREST: calcinosis, Raynaud, esophageal dysmotility, sclerodactyly, telangiectasia) with anti-centromere antibodies;
  • diffuse form with anti-Scl-70 (topoisomerase);
  • scleroderma renal crisis: sudden severe hypertension and AKI, treated with an ACE inhibitor.
• Sjögren syndrome: dry eyes and mouth, parotid swelling, anti-Ro and anti-La, and an increased lymphoma risk.
• Inflammatory myopathies:
  • proximal symmetric weakness with high CK;
  • dermatomyositis: heliotrope rash and Gottron papules, with a link to cancer (screen adults, including nasopharyngeal cancer in Southeast Asians);
  • treated with steroids and immunosuppressants.
• Antiphospholipid syndrome: venous or arterial thrombosis or pregnancy loss with lupus anticoagulant, anticardiolipin or anti-beta2 glycoprotein I antibodies on two tests 12 weeks apart. Treated with warfarin (DOACs are less effective in high-risk patients).
• Polymyalgia rheumatica: people over 50 with shoulder and hip girdle aching and stiffness and a high ESR. Responds dramatically to low-dose prednisone.
• Giant cell arteritis:
  • people over 50 with a new headache, scalp tenderness, jaw claudication, visual loss and a high ESR;
  • give high-dose steroids immediately to prevent blindness, then confirm with temporal artery biopsy or ultrasound.
• Other vasculitides:
  • Takayasu arteritis (young Asian women, absent arm pulses);
  • Kawasaki disease (children);
  • polyarteritis nodosa (hepatitis B);
  • ANCA vasculitis (granulomatosis with polyangiitis: sinuses, lungs and kidneys).

Bone tumors and metabolic bone disease in adults

• Metastases are the most common bone tumors: lytic (lung, kidney, thyroid, myeloma) or blastic (prostate).
• Multiple myeloma:
  • older adults with CRAB features: hyperCalcemia, Renal failure, Anemia and lytic Bone lesions;
  • rouleaux, an M spike on serum protein electrophoresis, free light chains (Bence Jones protein) and more than 10% clonal plasma cells in the marrow;
  • bone scans miss lytic lesions, so use skeletal survey or whole-body low-dose CT.
• Paget disease of bone: high ALP, bone pain, enlarged skull and deafness, treated with bisphosphonates.
• Osteoporosis:
  • a DXA T-score of −2.5 or less, or a fragility fracture;
  • treated with calcium and vitamin D, exercise, fall prevention, bisphosphonates (alendronate; take upright with water) or denosumab.
• Primary bone tumors are covered in orthopedics.

Dermatology

• Describing lesions:
  • flat lesions: a macule (under 1 cm) or patch;
  • raised solid lesions: a papule (under 1 cm), plaque or nodule;
  • fluid-filled: a vesicle (under 1 cm) or bulla; a pustule contains pus;
  • a wheal is transient (urticaria);
  • secondary changes include scale, crust, erosion, ulcer and lichenification.
• Skin infections and infestations:
  • scabies: intensely itchy papules and burrows in the finger webs, wrists, waist and genitals, worse at night, with household members also itching. Treated with permethrin 5% cream from the neck down (repeat in 1 week), treating all contacts at once and washing bedding; ivermectin for crusted scabies;
  • impetigo: honey-colored crusts (S. aureus, S. pyogenes), treated with topical mupirocin or oral antibiotics. Post-streptococcal GN can follow;
  • cellulitis and erysipelas: treated with oral or IV antistaphylococcal and antistreptococcal antibiotics;
  • dermatophytoses (tinea): annular scaly plaques with central clearing (corporis, cruris, pedis, capitis), diagnosed by KOH and treated with topical azoles or terbinafine. Tinea capitis needs oral griseofulvin or terbinafine. Steroid creams cause tinea incognito;
  • pityriasis versicolor (Malassezia): hypo- or hyperpigmented scaly macules on the trunk with a "spaghetti and meatballs" KOH pattern, treated with selenium sulfide or azoles;
  • herpes zoster: a painful dermatomal vesicular rash, treated with acyclovir or valacyclovir within 72 hours. Zoster in a young adult should prompt an HIV test, and eye involvement (Hutchinson sign) needs ophthalmology;
  • leprosy: hypopigmented anesthetic patches and thickened nerves (see public health).
• Eczema and psoriasis:
  • atopic dermatitis: itchy flexural eczema with a personal or family history of atopy, treated with emollients, topical steroids and calcineurin inhibitors;
  • contact dermatitis: irritant, or allergic (nickel, cosmetics, plants) with a delayed type IV reaction;
  • psoriasis: well-demarcated erythematous plaques with silvery scale on the extensor surfaces, scalp and nails (pitting, onycholysis), with the Koebner phenomenon and Auspitz sign. Treated with topical steroids and vitamin D analogs, phototherapy, methotrexate and biologics. Avoid systemic steroids, which can cause a pustular flare on withdrawal. It is linked to metabolic syndrome.
• Acne vulgaris: comedones, papules and pustules, treated with topical retinoids and benzoyl peroxide, oral doxycycline, and isotretinoin for severe nodular acne (teratogenic, so pregnancy prevention is needed).
• Severe cutaneous adverse drug reactions:
  • Stevens-Johnson syndrome (under 10% skin detachment) and toxic epidermal necrolysis (over 30%): fever and flu-like symptoms, then painful dusky macules, blisters, mucosal erosions and a positive Nikolsky sign, 4 to 28 days after starting the drug;
  • common culprits: carbamazepine (HLA-B*15:02 in Southeast Asians), allopurinol (HLA-B*58:01), sulfonamides, phenytoin, lamotrigine and nevirapine;
  • stop the drug immediately, give burn-unit-style supportive care, eye care and fluids; never rechallenge;
  • DRESS: rash, fever, eosinophilia, lymphadenopathy and hepatitis 2 to 8 weeks after the drug.
• Skin signs of systemic disease:
  • malar rash sparing the nasolabial folds and discoid lesions (SLE);
  • acanthosis nigricans (insulin resistance, sometimes gastric cancer);
  • erythema nodosum: tender shins, from TB, streptococcal infection, sarcoidosis, IBD, pregnancy and drugs;
  • pyoderma gangrenosum (IBD);
  • necrobiosis lipoidica (diabetes);
  • palpable purpura (vasculitis);
  • Janeway lesions and Osler nodes (endocarditis);
  • xanthomas (hyperlipidemia).