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Connective Tissue Diseases Adam Wray, D.O. September 7, 2004.

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Presentation on theme: "Connective Tissue Diseases Adam Wray, D.O. September 7, 2004."— Presentation transcript:

1 Connective Tissue Diseases Adam Wray, D.O. September 7, 2004


3 ANA Assay  Classic ANA immunofluorescence is still considered first line screening test for AI-CTD  Historically, rodent cells rather than human cells were used as the substrate  Rodent cell nuclei lack some autoantigens present in human cell nuclei (Ro antigen)  1-2% of SLE patients are ANA (-) using human tumor cell line base substrate (Hep-2)  Hence, “ANA negative SLE” a historical phenomenon  Titer of <1:160 using human tumor cell line substrate has little clinical utility

4 ANA Immunofluorescence Patterns

5 Drug Induced ANA/SLE  Procainamide  Hydralazine  Isoniazid  Chlorpromazine  Phenytoin  Methyldopa  Minocycline


7 Lupus Erythematosus  Chronic Cutaneous LE –DLE –Verrucous LE –Lichen Planus-LE overlap. –Chiblain LE –Lupus Panniculitis (LE profundus) With DLE With Systemic LE

8 Discoid LE  Young adults. F:M=2:1  Cat’s Tongue (Langue au chat) = carpet tacks  Lesions heal centrally first with atrophy, scarring, and dyspigmentation  Up to 24% will have mucosal involvement.  95% of cases confined to the skin at the onset and will remain so.



11 Discoid LE  Unusual for lesions below neck without lesions above the neck  Spontaneous involution with scarring is common  Progression to SLE is rare and may be identified by abnormal labs. –ANA – elevated –Leukopenia, hematuria, or albuminuria

12 Histology  Thinned epidermis  Loss of normal rete ridges  Follicular plugging  Hydropic changes of basal layer  Lymphocytic perivascular infiltrate  Increase interstitial mucin depositon  Pilosebaceous atrophy discriminates from SCLE  DIF is positive more than 75% of cases with Igs located at DEJ


14 Treatment  SUNSCREEN!!!!  Topical steroid, high potency with occlusion if needed.  Intralesional Injection with Kenalog  Antimalarials: safest and most beneficial system therapy. –Plaquenil for 3 months, if no response switch to Aralen. –If response is still incomplete, add Quinacrine, since this won’t increase retinal toxicity

15 Verrucous LE  AKA hypertrophic LE  Resembling KA or hypertrophic LP  Treatment with TAC or Intralesional  Also can be treated with Accutane or Plaquenil.

16 Verrucous LE  2% of patients with chronic cutaneous LE  Histo: epidermis is papillomatous, hyperplastic, and surmounted by hyperkeratotic scale

17 LE-LP Overlap syndrome  Large atrophic hypopigmented bluish-red patches and plaques.  Fine telangiectasia and scale usually present  Response to treatment is poor  Dapsone or Accutane maybe effective

18 Chilblain LE  AKA lupus pernio  Chronic, unrelenting form of LE with fingertips, rims of ear, calves and heels in women.  Chilblain lesions are due to cold  Usual LE treatment


20 LE Panniculitis  AKA LE Profundus  Deep subcutaneous nodules 1-4cm  Head, face, and upper arms  Woman age 20-45  Histology shows lymphocytic panniculitis, hyaline degeneration of the fat, hyaline papillary bodies. Over lying epidermis shows hydropic changes and follicular plugging  Treatment with Antimalarials.



23 SCLE  Subacute cutaneous LE –Papulosquamous –Annular –Syndromes commonly exhibiting similar morphology Neonatal LE Complement deficiency syndromes

24 SCLE  Typically photosensitive  Lesions confined to sun-exposed skin  Regular association with anti-Ro antibody (SS-A)


26 SCLE  Psoriasiform, polycyclic annular lesions  Shawl distribution: V neck, upper outer and inner arms.  ¾ of the patients have arthralgia  20% have leukopenia  80% have positive ANA  Associated with HLA-DR3-Positive.

27 Drugs triggering anti-Ro antibodies and thus lesions of SCLE  HCTZ  NSAIDS  Diltiazem  Griseofulvin  Terbinafine  Lesions may or may not clear once the medication is discontinued.




31 Neonatal LE  Annular scaling erythematous macules and plaques  Appear on head and extremities  First few months of life in babies born to mothers with LE, RA, or other connective tissue disease  Resolve spontaneously by 6 month of age  HALF of the patients have associated congenital heart block, usually 3 rd degree

32 Neonatal LE  Lesions histologically identical to SCLE  Almost 100% have anti-Ro antibodies  Unlike adult SCLE, lesions have predilection for the face, especially periorbital region  Lesions typically resolve without scarring  Other internal findings –Hepatobiliary disease –Thrombocytopenia



35 Acute Cutaneous LE  Characteristic butterfly facial erythema  May last from days to several weeks  Bullous lesion occur as single or grouped vesicle or bullae  Subepidermal bulla containing neutrophils.  HLA-DR2 positive  Minute telangiectasias appear in time on the face or elsewhere and commonly appear about the nail folds.  Rowell Syndrome: EM-like lesion dominant in LE



38 Systemic LE  Young to middle age women  Skin involvement occur 80% of the case  American Rheumatism Association has 11 criteria  If 4 or more of the criteria are satisfied, the patient is said to have SLE


40 ARA SLE criteria  Malar Erythema  Discoid Lupus  Photosensitivity  Oral Ulcers  Arthritis  Serositis  Nephritis  Hematologic  CNS Changes  Immunologic disorder  ANA


42 Systemic Manifestation.  Arthralgia is the earliest abnormality.  95% of SLE patient will have arthralgia.  Avascular necrosis of femoral head.  Thrombosis in vessels secondaary to presence of lupus anticoagulant.  Renal involvement in nephritic or nephrotic type.  Mycocarditis, cardiomegly, EKG changes.

43 Systemic Manifestation.  CNS involvement  Idiopathic thrombocytopenic purpura.  Sjogren’s syndrome  Mixed with dermatomyositis

44 Treatment of SLE  Treatment depending on the organ system(s) involved.  Skin, musculoskeletal, and serositis-type manifestations generally respond to treatment with hydroxychloroquine and nonsteroidal anti-inflammatory medications.  Porphyria cutaneous tarda may co-exist with LE, in this case, Plaquenil is TOXIC!!!  More serious organ involvement, such as CNS involvement or renal disease, often necessitates immunosuppression with high-dose steroids and cyclophosphamide.  Stop smoking!




48 Dermatomyositis  Poikiloderma  Gratton's sign - flat-topped violaceous papules  Heliotrope - reddish -purple flush around the eyes  Over knuckle streak erythema  Shawl pattern  Bimodal distribution  Calcinosis Cutis may occur in over half of the children with DM  Associated with Malignancy in 10-50% of adults


50 Dermatomyositis  Symmetrical muscle weakness  assoc c malignant neoplasm when over 40  periungual telangiectasia  Prednisone 1mg/kg with slow taper  Sunscreen, antimalarial  Mechanics hand: hyperkeratosis, fissuring, scaling involvement in the palm of the hand.

51 Muscle involvement  Symmetrical muscle weakness  Unable to raise arms to comb their hair  Cardiac involvement with cardiac failure in terminal phase  Amyopathic dermatomyositis or dermatomyositis sine myositis: DM without muscle changes

52 Childhood DM  Brunsting type –Slow course –Progressive weakness –Calcinosis –Steroid responsiveness  Banker type –Vasculitis of muscles and GI tract –Rapid onset –Severe weakness –Steroid unresponsiveness










62 Scleroderma  characterized by symmetric thickening, tightening, and induration of the skin of the fingers and the skin  These changes may affect the entire extremity, face, neck, and trunk (thorax and abdomen).  Occurs in localized and systemic forms

63 Localized Morphea  Smooth, hard, somewhat depressed, yellowish white, or ivory-colored lesions.  Common on the trunk  Margins surrounded by light violaceous zone or by telangiectasias.  Resemble pigskin (prominent follicular orifices)  Slowly involute over a 3-5 year period.

64 Generalized Morphea  Widespread hard indurated plaques.  No systemic involvement  Patient appear young because of the firmness of the skin.  Resolution less likely than the localized version.



67 Atrophoderma of Pasani and Pierini  Reduction of thickness of dermal connective tissue  Upperback and lumbar sacral area  Benign course, usually resolve after few months or few years.  No effect treatment  Variant of morphea.


69 Linear Scleroderma  Linear lesions extend to length of arms or leg  Begin first decade of life  May also occur parasagitally down the forehead, known as en coup de sabre  Parry-Romberg syndrome: progressive facial hemiatrophy, epilepsy, exophalmos, and alopecia, maybe a form of linear scleroderma.




73 CREST Syndrome  AKA Thibierge-Weissenbach Syndrome.  Systemic sclerosis may be limited to the hands, and is called acroslerosis.  Not as severe as PSS  ANA shows anticentromere antibody, and is highly specific.  Most favorable diagnosis



76 Progressive Systemic Sclerosis  Raynaud’s is the first manifestation of PSS most of the time and is eventually nearly always present  Round fingerpad sign: loose the normal peaked contour and appear round from the side.  Pterygium inversum unguis: distal part of nailbed remains adherent to ventral surface of nail plate. Seen also in LE

77 Progressive Systemic Sclerosis  75% have dilated nail fold capillary loops  Esophageal involvement in 90% of patients  Pulmonary fibrosis  Cardiac involvement  Articular pain, swelling, polyarthritis.

78 Prognosis  Skin involvement after 1 year of diagnosis:  Group I – sclerodactyly alone – 71% 10 year survival rate  Group II - Skin stiffness above metacarpal- phalangeal joints but not involving trunk – 58% survival rate.  Group III – truncal involvement – 21% survival.

79 LAB Finding  Topoisomerase I (formerly Scl–70) is present in 20-30% of patients with diffuse disease (absent in limited disease) and has an increased association with pulmonary fibrosis  Anticentromere antibodies are present in about 60-90% of patients with limited disease and 10-15% with diffuse disease.

80 Histology  Increased collagen bundle and thickness of the dermis  Pilosebaceous units are absent. Eccrine glands and ducts are compressed by collagen.  Eccrine glands present at the mid dermis rather than at the junction of dermis/subQ fat.

81 Treatment  Symptomatic tx  Treatment aimed at minimizing complications  Regular massage, warmth, and protection from trauma  No smoking



84 Eosinophilic Fasciitis  Patient engaging in strenuous muscular effort few days or week before acute onset of weakness. Follow by severe induration of the skin and subQ tissue of forearms and legs.  Coarse peau d’orange appearance.  Groove sign: depression follows the course of underlying vessels when arms are held laterally. Represents line of demarcation between muscle groups  Excellent response to corticosteroid.

85 Comparison of deep morphea and eosinophilic fasciitis. A Note the ‘pseudo-cellulite’ appearance of the involved skin of the thigh in deep morphea. B In eosinophilic fasciitis, the level of fibrosis is also deep.

86 Histology  Patchy lymphocytic and plasma cell infilrate in the fascia and subfacial muscle and great thickening, 10-50 times normal of the fascia.


88 Mixed Connective Tissue Disease  Mixed features of scleroderma, SLE, and dermatomyositis  IgG deposition in speckled (particulate) pattern in epidermal nuclei of normal skin on DIF is a distinctive finding in MCTD  Treatment with daily dose of prednisone 1mg/kg shows good improvement.  Most patients have anti-U1RNP antibodies

89 Sjogren’s Syndrome  AKA Sicca syndrome  Triad of keratoconjunctivitis sicca, xerostomia, and rheumatoid arthritis.  RF is usually positive  Elevated C-reactive Protein, IgG, IgA, and IgM  80% has anti-Ro/SSA antibody.  >50% have anti-La/SSB antobodies  Only symptomatic treatment available.  Labial salivary gland biopsy most definitive test

90 Schirmer test  Assesses lacrimal gland function  Whatman paper wick folded over eyelid for 5 minutes  <5mm tear film migration = lacrimal gland dysfunction

91 Rheumatoid Nodules  20-30% of RA patients  Subcutaneous nodules  Found anywhere on the body  Histologically shows dense foci of fibrinoid necrosis surrounded by histiocytes in palisaded arrangement.


93 Relapsing Polychondritis  Intermittent episodes of inflammation of the articular and nonarticular cartilage eventuating in chondrolysis.  MAGIC syndrome = Behcet’s + Relapsing Polychondritis (Mouth And Genital ulcers with Inflamed Cartilage)  Treatment with Dapsone for few weeks, then maintenance for 4-6 asymptomatic months.


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