TITLE: Connective Tissue Diseases
SOURCE: Grand Rounds Presentation, UTMB, Dept. of Otolaryngology
DATE: February 16, 2000
RESIDENT PHYSICIAN: Edward Buckingham, M.D.
FACULTY PHYSICIAN: Byron J. Bailey, M.D.
SERIES EDITOR: Francis B. Quinn, Jr., M.D.

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• -Autoimmune multisystem disease.
• -Prevalence 1in 2,000; 9 to 1 female to male; or 1 in700 women; 1 in 245 black women
• -Peak age of onset 15-25
• -Unknown cause, pathologic process is immune complex deposition
• -Systemic manifestations include photosensitive skin eruptions, serositis, pneumonitis, myocarditis, nephritis, CNS involvement
• -Specific labs- native(double stranded) DNA, SM antigen, many others often positive
• -procainamide, hydralazine, hydantoins, penicillin and sulfonamides may precipitate lupus like reaction
• - LE cell is specific

Head and Neck Manifestations

• -Skin and mucosal lesions
• -Malar or "butterfly" rash first sign of disease in 50%,
• -Erythematous maculopapular eruption most common head neck and chest may be pruritic and follow sun exposure
• -Oral ulcerations- superficial with erythematous halo, may increase to 2 cm, painful
• -3-5% ulceration or perforation of nasal septum
• -Larynx and trachea involvement rare- TVC thickening, paralysis, cricoarytenoid arthritis, subglottic stenosis
• -Acute enlargement of parotid in 10%, may be unilateral, tender confused with acute parotitis
• -Xerostomia in some
• -Neuropathy cranial nerves affected in 15%
• -Discoid lupus-subtype with cutaneous lesions with significant scarring, no visceral involvement

• -Avoidance of sun exposure use of sunscreens
• -NSAIDS
• -topical and systemic steroids
• -antimalarials
• -low-dose methotrexate
• -azothioprine, cyclophosphamide restricted to cases with serious visceral involvement
• -symptomatic treatment- saliva substitutes, mouthwashes, Klack’s solution, (tetracycline, cortisone, benadryl, nystatin)
• -postprandial rinses with H2O2 and H2O 50:50

• -inflammation of synovial tissue with symmetric involvement of peripheral joints, hand, feet, wrists commonly
• -can also affect nonarticular muscular structures(tendon, ligaments, fascia)
• -occasionally systemic disease such as vasculitis, pulmonary fibrosis
• -inflammatory cell infiltrates (lymphocytes), synovial proliferation responsible for pathogenesis
• -high incidence of HLA Dw4 locus positive suggesting inherited contribution
• -occurs in 1% of the population, women 2-3 times men, 4^th – 5^th decade, also distinct juvenile form
• -onset may be acute, more often insidious, progressive joint involvement
• -morning stiffness lasting greater than 30 minutes, or after prolonged inactivity
• -subcutaneous rheumatoid nodules
• -synovial fluid shows inflammation 2K to 75K WBC’s 50% PMN’s
• -diagnosis clinical, rheumatoid factor positive within 12 months of onset in 90 % of patients
• -other tests RA associated nuclear antigen (RANA), anti-RA-33,
• -diagnostic criteria p 195 Baileys

• -articular involvement of the ossicles, TM joint, cricoarytenoid joints, cervical spine
• -TM joint involvement common 55% symptomatic, up to 70% evident on X-ray
• -juvenile RA can cause micrognathia
• -RA most common cause of arthritis of cricoarytenoid joint
• -30 % of RA patients hoarse, 86% show patholigic involvement of joint
• -exertional dyspnea ear pain, globus sensation all attributed to C-A joint involvement
• -hoarseness also caused by rheumatoid nodules or ischemic recurrent nerve paresis or paralysis
• -can present with stridor requiring local and systemic steroids and possible tracheostomy
• -possible CHL from ossicular chain involvement, TM may lose stiffness
• -also described unexplained SNHL associated especially with rheumatoid nodules
• -RA of spinal column predilection for cervical and can lead to subluxation

Treatment

• -physical therapy, daily exercise, splinting joint protection,
• -salicylates, NSAIDS, gold salts, penicillamine, hydroxychloroquine, immunosuppressive agents, systemic corticosteroids should in general be avoided
• -prognosis 10-15 yrs of disease 50% fully employed, 10 % completely incapacitated, 10-20% complete remission

• -immune-mediated destruction of exocrine glands
• -not to be confused with Mikulicz’s disease (swelling due to nonspecific lymphocytic infiltrate accompanying nonconnective tissue diseases such as hyperlipoproteinemia, malnutrition, diabetes, cirrhosis, tuberculosis, and sarcoidosis)
• -primary and secondary forms
• -primary or sicca syndrome- isolated disorder of lacrimal and salivary glands
• -seconcary- sicca complex when associated with any of the connective tissue diseases
• -occurs in 1% general population and 10-15% of RA patients
• -9 to 1 female preponderance, onset 40-60 yrs of age
• -increased risk of lymphoma, perhaps as high as 44 times risk
• -clinical manifestations- xerophthalmia and secondary keratoconjunctivitis, xerostomia,
• -can also affect skin, vagina, external genitalia, chronic bronchitis, GI tract, renal tubules
• -minor salivary gland biopsy demonstrates heavy lymphocyte infiltration
• - RF and ANA high in most patients, Sjogran’s syndrom A (Ro/SS-A) SS B (La/SS-B) noted in 60% and 30% of patients respectively
• -diagnostic criteria p 196 Bailey’s

Head and Neck Manifestations

• -80% c/o xerostomia most predominant symptom
• -diffuculty chewing, dysphagia, changes in taste, fissures of tongue and lips, increased dental caries
• -oral candidiasis
• -salivary quantification difficult and requires experience, quantitative salivary scintigraphy best
• -history of recent salivary gland enlargement, bilateral or unilateral, recurrent not persistent
• -eye complaints of dryness, burning, itching, and foreign body sensation
• -keratoconjunctivitis sicca- corneal abrasions with rose bengal staining
• -Schirmer I test (lacrimal production) 15 mm wetting after 5 minutes normal, 5-15 equivocal, less than 5 abnormal (15% normal subjects less than 5mm)
• -Schirmer II – stimulate with 10% ammonia 15 cm below nose, less than 10 mm abnormal
• -nasal crusting, epistaxis, hyposmia 2ndary to loss of nasal glandular secretions
• -diagnosis- history- Schirmer I if abnormal then Schirmer II or rose bengal staining abnormal or other supportive evidence ie. abnormal salivary flow then labial biopsy is indicated

• -symptomatic treatment increased oral intake, saliva substitutes, artificial tears
• -avoid decongestants, antihistamines, diuretics, and other drugs with anitcholinergic side effects
• -pilocarpine
• -candidiasis treat with clotrimazole or nystatin
• -close supervision by a dentist is essential
• -surveillance for any developing malignancy

• -also called systemic sclerosis
• -increased deposition of collagen in the interstitium and intima of small arteries and connective tissue
• -characterized by sclerotic skin changes often accompanied by multisystem disease
• -4-12 new cases per million per year, 3 or 4 to 1 female to male preponderance
• -average age of onset between 30 and 50 yrs
• -black women worse prognosis than white, men worse than women
• -initial presentation includes Raynaud’s phenomenon, edema of fingers and hands, skin thickening
• -visceral manifestations seen in the gastrointestinal tract, lung, heart, kidneys and thyroid
• -arthralgias and muscle weakness common complaints
• -four categories
  1. diffuse cutaneous- worse prognosis earlier and more extensive systemic involvement
  2. limited cutaneous- (formerly CREST-calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) ,more benign course fewer renal complications
  3. systemic sclerosis sine scleroderma- visceral manifestations of systemic sclerosis without skin changes.
  4. systemic sclerosis in overlap- concomitant SLE, polymyositis, RA
• -diffuse cutaneous- anti-ScL-70, limited cutaneous(CREST) anticentromere
• -elevated ESR, mild anemia of chronic disease, ANA, hypegammaglobulinemia, RF, LE cells, abnormal EKG in 50%(low voltage, axis deviation, intraventricular conduction deficits)

Head and Neck Manifestations

• -80% H&N complaints, 30% present with H&N complaint
• -tight skin, thin lips, vertical perioral furrows
• -skin changes due to underlying dermal and subcutaneous inflammatory process
• -edema precedes epidermal atrophy and loss of appendages
• -dysphagia is most common initial complaint
• -80% show distal 2/3 of esophagus pathology on barium swallow
• -decreased or absent peristalsis with mild to moderate dilation, hiatal hernia is common
• -decrease ability to open mouth initial complaint in 19%, 2ndary to skin changes
• -gingivitis and periodontal thickening are common, translucent zone around dental roots considered pathognomonic of scleroderma by some investigators
• -25 % report xerostomia, xerophthalmia or both
• -laryngeal involvement occurs with almost 50% c/o hoarseness
• -infrequently Raynaud’s of the tongue presents with blanching and dysarthria
• -infrequently trigeminal neuralgia and facial nerve palsy

• -treatment is symptomatic
• -calcium channel blockers in Raynaud’s
• -H₂ blockers for reflux
• -NSAIDS and low dose steroids may relieve arthralgias and myalgias
• -hand rehabilitation
• -intra-arterial reserpine decreases vasoconstriction promotes healing

• -group of disorders characterized by proximal muscle weakness and nonsuppurative inflammation of skeletal muscle
• -polymyositis and dermatomyositis subsets
• -5 cases per million per year, 2 to 1 female to male, onset 40 to 60 years, pediatric variant 5-15 yrs old
• -criteria- proximal muscle weakness, elevated serum creatinine kinase levels, myopathic changes on electromyography, muscle biopsy evidence of inflammation (lymphocytic)
• -diagnosis definitive with all four, probable with three, possible with two
• -dermatomyositis requires characteristic skin rash with above
• -anti-tRNA synthetases
• -may be associated with other connective tissue diseases
• -up to 20 % associated with malignancy, lung, ovary, breast, stomach most common parotid, tonsil reported
• -reported increase incidence of nasopharyngeal carcinoma in patients with dermatomyositis where endemic

• -manifestations reflect proximal muscle weakness
• -weakness of neck muscles
• -difficulty with phonation and deglutition, nasal regurgitation,
• -dysphagia secondary to involvement of upper esophagus, cricopharyngeus, pharynx, and sup. Constrictors
• -dysfuction in swallow can result in aspiration and pneumonia
• -skin and mucous membrane lesions of dermatomyositis vary-predilection for eyelids, nose, and cheeks

• -steroids for symptomatic patients
• -methotrexate and other immunosuppressive agents reserved for nonresponders
• -H₂ blockers, metoclopromide

• -episodic recurring inflammation of cartilaginous structures, eventually replaced by fibrosis
• -women more often than men
• -Age of onset 35-45, no racial predilection
• -can affect any cartilagenous structure including heart valves and large arteries
• -diagnostic criteria- recurrent chondritis of auricles, nonerosive inflammatory polyarthritis, chondritis of nasal cartilages, inflammation of ocular structures, chondritis of laryngeal or tracheal cartilages, cochlear (SNHL, tinnitus) of vestibular damage (vertigo)
• -ESR elevated, moderate leukocytosis, mild to moderate anemia
• -histologically- loss of basophilic staining of cartilage, perichondral inflammation, cartilage destruction and replacement by fibrous tissue

Head and Neck Manifestions

• -auricular chondritis, nonerosive arthritis most common
• -sudden onset erythema, pain, sparing EAC feature in 33%, developes in 90%, occas. LAD
• -resolution in 5-10 days with or without treatment
• -may have concomitant serous otitis or SNHL, 49% inner ear symptoms
• -nasal chondritis developes in 75% does not always coincide with auricular symptoms
• -nasal and auricular chondritis act similar both causing deformity and dysfunction
• -layngeal involvement nonproductive cough progressses to hoarseness and stridor
• -53% will have airway involvement

Treatment

• -salicylates, ibuprofen for symptomatic relief
• -steroids for life threatening manifestations
• -antileprosy drug, dapsone reduces lysozymes decreasing inflammatory response

• -coined in 1972
• -describes a distinct entity with coexisting features of SLE, scleroderma, and polymyositis
• -high titers of anti-U1 RNP, a ribonucleoprotein antibody
• -prevalence unknown, 80% female, onset 30-60 yrs.
• -diagnostic criteria elevated titers of anti-U1 RNP plus three of either a) hand edema, b) synovitis c) myositis, d) Raynaud’s phenomenon, or e) acrosclerosis
• -pulmonary involvement is common
• -cardiac and renal involvement in 25%

• -combination of features of other CTD
• -mucocutaneous changes, malar rash, discoid lupus, sclerodermatous skin changes, oral mucosal ulceration, nasal septal perforation, esophageal dysfunction

• -steroid therapy for symptomatic relief
• -immunosuppressives only after complications involving vital organs develop

• -collective term for large group of diseases
• -result in inflammation of small vessels, arterioles, capillaries, and venules
• -most cases related to circulating and deposited immune complexes
• -skin clinically involved virtually always, hemorrage or classic purpura
• -involvement of major organ systems is less common

• -petechiae and purpura of oral and nasal mucosa
• -angioedema
• -serous otitis media

• -usually self-limiting particularly when only skin is involved
• -if systemic involvement present or underlying disease (ie.cryoglobulinemia) more aggressive therapy warranted

• -prototype of vasculitides
• -males two to three times more often than females
• -50-60 yrs old
• -hepatitis B antigen in 30%
• -small and medium arteries, aneurysms
• -tissues include GI tract, hepatobiliary system, kidney, pancreas, and skeletal muscles
• -non-specific multisystem complaints (malaise, weight loss, anorexia, fever)
• -progressive arthritis, myopathy, neuropathy, hepatic and renal failure, GI bleeding

• -few and primarily involve ear
• -sudden bilateral SNHL infrequent presentation, vestibular disturbance
• -proposed mechanism is thromboembolic occlusion of inner ear end arteries
• -rarely- ulceration of nasal, buccal, soft palate mucosa, cranial nerve palsies VIIth most common

• -Steroids

• -resembles polyarteritis nodosa
• -triad of systemic vasculitis, asthma, peripheral and tissue eosinophilia
• -nasal symptoms also prominent
• -unlike PAN, lungs virtually always involved
• -malaise, night sweats, fever, weight loss, myalgias
• -peripheral eosinophilia as high as 74%, elevated ESR

• -nasal obstruction, rhinnorhea, nasal polyps, sinusitis
• -25% severe nasal crusting recurring after removal in 24-48 hrs
• -occasional septal perforation
• -subcutaneous nodule
• -history of allergy

• -corticosteroids

• -necrotizing granulomatous vasculitis of upper airway, lower airway, and kidney
• -bilateral pneumonitis (95%), chronic sinusitis (90%), mucosal ulceration of nasopharynx (75%) evidence of renal disease (80%)
• -hallmark pathologic lesion necrotizing granulomatous vasculitis
• -antineutrophil cytoplasmic antibody (c-ANCA), sensitivity (65-90%) high specificity
• -need tissue to confirm diagnosis, often takes 3-4 biopsies, open pulmonary biopsy occas. necessary
• -most commonly involved and accessible tissue is nasopharynx
• -untreated mortality of 90% at two years

• -nasal symptoms- crusting, epistaxis, rhinorrhea, erosion of septal cartilage, saddle deformity, recurrent sinusitis
• -oral cavity- hyperplasia of gingiva, gingivitis,
• -upper airway- edema, ulceration of larynx (25%), significant subglottic stenosis (8.5%)
• -Otologic- (20-25%)- serous otitis media, CHL, suppurative otitis media possibly with grannulation tissue, SNHL, pinna changes similar to polychondritis, facial nerve palsies

• -meticulous dental and nasal care, removal of crusts from eustachian tube orifices, middle ear drainage
• -cyclophosphmide 2 mg/kg plus prednisone 1 mg/kg achieved remission in 93% of patients
• -azathioprine or methotrexate alternative to cyclophosphamide
• -isolated sinus disease- low dose steroids, topical steroids, saline irrigation, antibiotics as needed
• -airway compromise alleviated with systemic steroids,
• -subglottic stenosis may warrant tracheotomy

• -temporal is form of giant cell with only extracranial vessels affected
• -focal granulomatous inflammation of medium and small arteries
• -most common vasculitis
• -prevalence increases with age to 850/100,000 age 80 and older
• -symptoms reflect cranial blood supply
• -headache (constant , boring) most common initial complaint, 47%, 90% develop
• -ESR usually greater than 50 mm/hr
• -confirmation from temporal artery biopsy of symptomatic side, 5-7 cm
• -if negative biopsy contralateral side
• -false negative rate 5-40%

• -temporal artery tender and erythematous 50% of time
• -scalp often tender
• -jaw claudication 50%
• -lingual claudication 25%
• -vertigo and hearing loss reported
• -ascending pharyngeal artery involvement can lead to dysphagia
• -cranial nerve deficits, vertebrobasilar insufficiency, psychosis reflect intracranial disease
• -blindness occurs in 1/3 of untreated patients- field deficits, amaurosis fugax

• -prednisone
• -normalization of ESR and symptoms therapeutic guideline
• -treatment may be required for up to two years

• -accompanying syndrome in 50% of patients with giant cell arteritis
• -clinical syndrome of muscular pain, morning stiffness of proximal muscles, increased ESR without inflammatory joint or muscle disease
• -systemic symptoms- low-grade fever, weight loss, malaise
• -responds well to low-dose prednisone if isolated
• -if with giant cell high dose initially then adjusted

• -vasculitis with triad of oral and genital ulcers and uveitis or iritis
• -aphthous-like ulcers, characteristically punched out with or without surrounding erythema, covered with pale pseudomembrane
• -painful, occur in clusters on lips, gingiva, buccal mucosa, tongue, less often on palate, oropharynx
• -genital ulcers similar in appearance
• -healing in few days to weeks with some scarring
• -symptoms may occur simultaneously or months apart

• -progressive SNHL, tinnitus, and vertigo have been associated with Behcet’s
• -may also have ulceration of nasal, laryngeal, tracheal mucosa
• -morbidity from CNS involvement, bowel dysfunction, large vessel arteritis
• -azathioprine or methotrexate may be beneficial although not documented

• -rare disease of young adults
• -vestibuloauditory dysfunction, interstitial keratitis, and nonreactive syphilis test
• -symptoms frequently begin after URI
• -vestibuloauditory symptoms usually bilateral can include fluctuating hearing loss, vertigo, tinnitus, and aural pressure, similar to Meniere’s but bilateral
• -occular symptoms of photophobia, lacrimation, and eye pain
• -may resolve spontaneously and reappear months later
• -when advanced, hearing loss progressive and severe with decreased or absent vestibular responses on caloric testing
• -ear symptoms may precede or follow ocular disease
• -eye symptoms easily controlled with topical steroids and atropine
• -evidence exists that hearing loss may be avoided if treated with steroids within 2 weeks of onset

Kawasaki Disease

• -AKA-mucocutaneous lymph node syndrome
• -disease of pediatric age group
• -fever, conjunctivitis, red dry lips, erythema of the oral mucosa, polymorphous truncal rash, desquamation of the fingers and toes, and cervical lymphadenopathy
• -oral cavity erythema and cervical adenopathy are presenting symptoms
• -cardiac abnormalities cause 1-2% mortality rate

Posted 02/22/2000