Connective Tissue Diseases

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

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

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 3rd 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.