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🌱 來自: Huppert’s Notes
Other Rheumatologic Conditions🚧 施工中
Other Rheumatologic Conditions
Polymyalgia rheumatica (PMR)
• Clinical features:
- Syndrome of neck, shoulder, and hip girdle stiffness that is typically worse after immobility; associated with elevations in markers of systemic inflammation (e.g., ESR, CRP)
- 50% of patients with GCA have PMR, and 20% of patients with PMR have GCA
• Diagnosis:
- A diagnosis of exclusion made after ruling out myopathies (for myopathy, weakness > pain; for PMR, pain > weakness) or non-systemic periarticular syndromes, such as adhesive capsulitis
- May be difficult to distinguish from seronegative RA as some patients have a distal polyarthritis; when present, erosive disease favors a diagnosis of RA
- Improves briskly with prednisone 12.5–20 mg daily and failure to improve as expected with steroids should raise suspicion for the presence of an alternative diagnosis
• Treatment: Prednisone 20 mg/day and prolonged taper (often 1–2 yr)
Behçet syndrome
• Pathogenesis: Not fully elucidated; increased risk with HLA-B51 allele implicates cell-mediated autoimmunity (US cases tend not to be associated with this HLA type)
• Epidemiology: Incidence 1/100,000 individuals annually in the United States; 400/100,000 individuals annually in Turkey. Also relatively more prevalent in Iran, Saudi Arabia, Greece, Japan, Korea, and China, tracking with the distribution of the HLA-B51 allele. Age of onset typically 20–30 yr.
• Clinical features:
- Derm: Recurrent genital and oral ulcers (the latter occur in nearly 100% of patients and are painful, unlike those that occur in SLE); erythema nodosum with ulceration; pseudofolliculitis/nodular cystic acne of the face and neck
- Vascular: Vasculitis with potential small (retinal), medium (mesenteric) and large (pulmonary, carotid, aortic, iliac, femoral) vessel involvement; venous and arterial thrombi (potentially IVC thrombosis, dural venous sinus thrombosis, arterial thromboses, and aneurysms)
- GI: Apthous ulcers of the ileum/cecum presenting with abdominal pain, anorexia, diarrhea, GI bleeding
- Articular: Inflammatory oligoarthritis in ~50% of patients with large joint-predominance (knees most common); sacroiliitis
- Ocular: Uveitis (anterior, posterior, or panuveitis); retinal vasculitis
- CNS: Headache, altered mental status; CSF may show elevated protein and leukocytosis; cranial neuropathies including CN VIII
• Diagnosis: See Table 9.11
TABLE 9.11 • International Criteria for Behçet’s Disease
- Pathergy: A skin prick is performed with a sterile needle, and the site is assessed 48 hr later. Patients who develop a pustule are deemed to have a positive test.
- DDx for recurrent oral ulcers: HSV, HIV, Crohn’s, nutritional deficiency (iron, zinc, folate, B1, B2, B6, B12), cyclic neutropenia, reactive arthritis, methotrexate
• Treatment:
- Oral and genital ulcers: Topical glucocorticoids for management of active lesions; colchicine for prevention of new genital lesions and erythema nodosum
- Arthritis: Colchicine for acute flares; azathioprine or TNFα inhibitors for chronic arthritis
- Thrombotic events: Anticoagulation, also consider immunosuppression with glucocorticoids
- Intestinal ulcer flares: High-dose glucocorticoids (1 mg/kg) with subsequent mesalamine or azathioprine
- CNS disease: High-dose glucocorticoids (1 mg/kg) with subsequent introduction of azathioprine
Relapsing polychondritis
• Pathogenesis: Not fully elucidated; involves episodic immune-mediated damage to cartilaginous tissues including the ears, nose, and proximal tracheobronchial tree
• Epidemiology: Incidence 3.5/million individuals annually, mean age at diagnosis 47 yr
• Disease categories:
- Primary: No evidence of a separate underlying rheumatic or hematologic disease
- Secondary (30%): Occurring in the context of GPA, RA, SLE, or myelodysplastic syndrome
• Clinical features:
- Inflammation of cartilaginous tissues: Auricular chondritis (red/tender cartilaginous ear with sparing of the lobe, 90% patients), nasal cartilage inflammation which can cause septal perforation and saddle nose deformity
- Articular manifestations: Episodic, migratory inflammatory oligoarthritis in ~70% patients, occurring contemporaneously with inflammation at other cartilaginous sites
- Airway disease: Subglottic tracheal stenosis; bronchiectasis
• Diagnosis:
- Clinical diagnosis typically made on the basis of auricular chondritis, saddle nose deformity, tracheobronchial involvement, and exclusion of other conditions
- If atypical manifestations, auricular cartilage biopsy during flare reveals perichondrium inflammatory cell infiltration
• Differential diagnosis:
- Ddx for auricular erythema: Otitis externa/auricular cellulitis
- Ddx for nasal inflammation/saddle nose deformity: GPA, Crohn’s, NK cell lymphoma, syphilis, leprosy, leishmaniasis
• Treatment:
- Flares of cartilaginous inflammation (auricular or nasal chondritis): Glucocorticoids first-line
- Tracheobronchial disease: Local glucocorticoid injections, stents for stenotic areas, CPAP
IgG4-related disease
• Pathogenesis: Not fully elucidated, but involves tissue infiltration with IgG4 plasma cells as well as copious lymphocytes, eosinophils, and dense fibrosis
• Epidemiology: Prevalence not yet described; M:F = ~3:1 for IgG4-related pancreatitis
• Clinical features:
- General patterns of disease: Tumefactive fibrotic organ infiltration with predominant involvement of exocrine organs. Preceding atopic disease is common but typically less active
- Ocular: “Orbital apex syndrome”/orbital pseudotumor causing proptosis
- Exocrine glands: Autoimmune pancreatitis (presenting with abdominal pain and/or obstructive jaundice; serum IgG4 is often elevated but a biopsy is typically needed to rule out malignancy); sclerosing cholangitis; inflammation/enlargement of the submandibular, parotid, and lacrimal glands
- Endocrine glands: Fibrosing thyroiditis, lymphocytic hypophysitis
- Vascular: Ascending or descending aortitis (histopathologically may not be a true vasculitis)
- Retroperitoneum: Retroperitoneal fibrosis and periaortitis
- Renal: Tumefactive lesions occasionally mistaken for renal cell carcinoma; tubulointerstitial nephritis
- Neuro: Pachymeningitis of the dura
• Diagnosis:
- Made by biopsy of involved tissue, with key findings of >30 IgG4+ plasma cells per high power field and characteristic dense lymphoplasmacytic infiltrate and “storiform” fibrosis
- Serum IgG4 is elevated in only 70–80% of patients
• Treatment:
- Prednisone 0.5 mg/kg daily for 2–4 weeks, then tapered over 3–6 months
- Mycophenolate, methotrexate, or azathioprine have been used as glucocorticoid-sparing remission-maintenance therapy, but have not been studied in clinical trials
- Rituximab can be used for relapsed or refractory disease
Adult-onset Still’s Disease (AOSD)
• Pathogenesis: Thought to be due to dysregulated innate immunity and thus it is an autoinflammatory rather than an autoimmune syndrome
• Diagnosis and clinical features:
- Yamaguchi Criteria for Adult-onset Still’s: See Table 9.12
TABLE 9.12 • Yamaguchi Criteria for Adult Onset Still’s Disease
- Complications may include hemophagocytic lymphohistiocytosis (HLH), disseminated intravascular coagulation, and fulminant hepatitis
• Differential diagnosis:
- Infectious:
• Bacterial: Staphylococcal toxic shock syndrome; Neisseria meningitidis infection; secondary syphilis; rickettsial, anaplasma, or erlichia infection
• Viral: Acute HIV; primary VZV or rarely zoster; EBV or CMV mononucleosis; parvovirus B19; dengue; chikungunya
- Malignant: Cutaneous lymphoma or leukemia; paraneoplastic dermatoses (pemphigus; Sweet syndrome)
- Autoimmune: SLE, dermatomyositis, MCTD
- Drug: DIHS (formerly DRESS); SJS/TEN
• Treatment: DMARDs such as methotrexate are effective for arthritis; IL-1 inhibitors are effective for fevers and other manifestations
Sarcoidosis
• Pathogenesis: Incompletely characterized but thought to involve dysregulated activation of CD4+ T cells and formation of granulomas (nodular collections of epithelioid macrophages) in multiple tissues
• Clinical features:
- Pulm (>90%): Bilateral hilar adenopathy, perilymphatic nodules, and ILD-related fibrotic changes (reticulation, honey-combing, traction bronchiectasis)
- Ocular (20–30%): Uveitis – usually anterior but can also be posterior
- Cutaneous (20–30%): Erythema nodosum; lupus pernio (facial rash involving violaceous plaques and nodules over the nose, nasal alae, malar areas, nasolabial folds, scalp, and hairline)
- Articular (5%): Polyarticular (and rarely erosive) arthritis typically affecting the ankles, knees, and wrists; typically resolves in weeks to months without intervention
- Musculoskeletal: Lytic bone lesions (10%), sarcoid myopathy (common but only symptomatic in 0.5–5% patients)
- Cardiac (10%): Heart block/conduction system disease, ventricular arrythmias, dilated cardiomyopathy. Consider cardiac PET or cardiac MRI if suspicion for cardiac involvement.
- Neuro: CN VII palsy most common, but CN II (optic neuritis), III, V, VIII and IX lesions can also occur. Aseptic meningitis and hypophysitis are less common manifestations.
- Exocrine glands: Parotitis resulting in sicca symptoms
• Sarcoidosis sub-syndromes: These syndromes obviate the need for diagnostic biopsy in most cases
- Asymptomatic bilateral hilar adenopathy (e.g., no fevers, night sweats, weight loss to suggest malignancy)
- Löfgren syndrome: Constellation of bilateral hilar adenopathy, erythema nodosum, migratory polyarthralgias/arthritis. 95% specific for sarcoidosis and obviates the need for biopsy
- Heerfordt syndrome (uveoparotid fever): Fever, uveitis, parotitis +/- CN VII palsy, associated with sicca symptoms
• Diagnosis: Biopsy of involved tissue (e.g., hilar lymph node, lung parenchyma) showing non-caseating granulomas (e.g., no central necrosis). Patients presenting with one of the sub-syndromes above may not require a biopsy unless diagnostic uncertainty is present.
• Treatment:
- Generally, treat disease if symptomatic but can often just monitor if asymptomatic
- Glucocorticoids (e.g., prednisone 20mg daily) for at least 8–12 months are the first-line therapy for symptomatic pulmonary and extrapulmonary disease
- For patients who have persistent disease activity or intolerable side effects with glucocorticoids alone:
• Methotrexate is effective for disease activity in multiple tissues
• Hydroxychloroquine and doxycycline/minocycline are effective for cutaneous disease
• TNFα inhibitors are used for patients with persistent disease activity despite non-biologic DMARD therapy
Fibromyalgia
• Pathogenesis: Thought to involve inappropriately strong or persistent sensory pain signals from neurons in the dorsal root ganglia and impairment of efferent adrenergic neurons that normally dampen pain sensation, causing allodynia and “temporal summation” of pain stimuli
• Epidemiology: Prevalence estimate 2–3% of population, F:M = 3:1
• Diagnosis and clinical features:
- There are multiple screening tools; one of the most simple ones is from the American Pain Society and the FDA (J Pain 2019;20:611) and involves pain at ≥6 body sites as well as insomnia (Table 9.13)
TABLE 9.13 • Fibromyalgia Diagnostic Criteria (2019 AAPT*)
- Key differential diagnostic considerations include depression, hypothyroidism, or adrenal insufficiency, which should be excluded
- Fibromyalgia often coexists with rheumatologic disease; thus, it is important to still pursue an appropriate workup in patients with clinical symptoms suggestive of an autoimmune disease
• Treatment:
- Aerobic exercise in a graded fashion
- Assess trauma history and treat co-morbid psychiatric disorders including anxiety, PTSD, substance use
- Gabapentin, pregabalin, and TCAs may be effective for both pain and insomnia; cyclobenzaprine can be useful if muscle spasms are present
Inherited Diseases of Connective Tissues
See Table 9.14
TABLE 9.14 • Inherited Connective Tissue Diseases