Presentation on theme: "Connective Tissue Diseases"— Presentation transcript:
1Connective Tissue Diseases Adam Wray, D.O.September 7, 2004
2Example of autoantibodies with considerable disease specificity and good for diagnosis are boxed. Anti-ds DNA and Sm for SLEMi-2 for classic dermatomyositisJo-1 for anti-synthetase syndromeScl-70 (aka topoisomerase) and centromere for different forms of systemic sclerosisHowever, most autoantibodies fall into the disease nonspecific category, as illustrated. As shown, high levels of U1RNP with overlapping features of all four of these AI-CTD defines the concept of MCTD
3ANA AssayClassic ANA immunofluorescence is still considered first line screening test for AI-CTDHistorically, rodent cells rather than human cells were used as the substrateRodent 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 phenomenonTiter of <1:160 using human tumor cell line substrate has little clinical utilityReference: Bolognia, Ch. 42, p. 592
4ANA Immunofluorescence Patterns Detection of antinuclear antibodies on Hep-2 tumor cells. A–D Homogenous pattern; speckled pattern; nucleolar pattern; Anti-centromere antibodies. E Anti-double-stranded DNA antibodies binding to the flagellate Crithidia luciliae by indirect immunofluorescence. These patterns have little disease specificity with exception of centromeric (discrete speckled) = CRESTPeripheral (rim) suggests antibodies to ds-DNA SLENucleolar suggests SScSpeckled (particulate) suggests presence of antibodies to U1RNP MCTD
5Drug Induced ANA/SLE Procainamide Hydralazine Isoniazid Chlorpromazine PhenytoinMethyldopaMinocyclineMinocycline recently added to the list.Reference Bolognia: Ch. 42, p. 592
6Predominant locations of inflammatory infiltrates in subsets of cutaneous lupus erythematosus . The types of cutaneous lupus erythematosus are: acute cutaneous lupus (ACLE), subacute cutaneous lupus (SCLE), chronic cutaneous lupus (CCLE), tumid lupus (TLE), and lupus panniculitis (LEP).The primary locations of the infiltrates are as follows: superficial dermis, ACLE and SCLE; superficial plus deep dermis and periadnexal, DLE; deep dermis, TLE; and subcutaneous fat, LEP.
7Lupus Erythematosus Chronic Cutaneous LE DLE Verrucous LE Lichen Planus-LE overlap.Chiblain LELupus Panniculitis (LE profundus)With DLEWith Systemic LE
8Discoid LE Young adults. F:M=2:1 Cat’s Tongue (Langue au chat) = carpet tacksLesions heal centrally first with atrophy, scarring, and dyspigmentationUp to 24% will have mucosal involvement.95% of cases confined to the skin at the onset and will remain so.
9Chronic cutaneous lupus erythematosus (CCLE) with discoid lesions Chronic cutaneous lupus erythematosus (CCLE) with discoid lesions. The ear is a common site of involvement. Note the central depigmentation and scarring. In addition to the obvious, intensely inflamed, indurated lesion on the side of the face, there is a small lesion in the uppermost portion of the concha of the ear.
10The widespread discoid lesions in this person resulted in depigmentation on the face, arms, and trunk.
11Discoid LEUnusual for lesions below neck without lesions above the neckSpontaneous involution with scarring is commonProgression to SLE is rare and may be identified by abnormal labs.ANA – elevatedLeukopenia, hematuria, or albuminuria
12Histology Thinned epidermis Loss of normal rete ridges Follicular pluggingHydropic changes of basal layerLymphocytic perivascular infiltrateIncrease interstitial mucin depositonPilosebaceous atrophy discriminates from SCLEDIF is positive more than 75% of cases with Igs located at DEJ
13prominent periadnexal localization of inflammation similar to SCLE
14TreatmentSUNSCREEN!!!!Topical steroid, high potency with occlusion if needed.Intralesional Injection with KenalogAntimalarials: 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
15Verrucous LE AKA hypertrophic LE Resembling KA or hypertrophic LP Treatment with TAC or IntralesionalAlso can be treated with Accutane or Plaquenil.
16Verrucous LE 2% of patients with chronic cutaneous LE Histo: epidermis is papillomatous, hyperplastic, and surmounted by hyperkeratotic scale
17LE-LP Overlap syndrome Large atrophic hypopigmented bluish-red patches and plaques.Fine telangiectasia and scale usually presentResponse to treatment is poorDapsone or Accutane maybe effective
18Chilblain LE AKA lupus pernio Chronic, unrelenting form of LE with fingertips, rims of ear, calves and heels in women.Chilblain lesions are due to coldUsual LE treatment
19Lupus pernio. Violaceous plaques on toes, some with scale.
20LE Panniculitis AKA LE Profundus Deep subcutaneous nodules 1-4cm Head, face, and upper armsWoman age 20-45Histology shows lymphocytic panniculitis, hyaline degeneration of the fat, hyaline papillary bodies. Over lying epidermis shows hydropic changes and follicular pluggingTreatment with Antimalarials.
21Lupus panniculitis. The deeply indented lesions of the arms represent lupus panniculitis. The patient also had lesions on the face, upper trunk, breasts, and thighs.
22There is a lobular panniculitis with a dense infiltrate of lymphocytes, plasma cells, and macrophages. Focal hyalinization of the adipocytes is present.
23SCLE Subacute cutaneous LE Papulosquamous Annular Syndromes commonly exhibiting similar morphologyNeonatal LEComplement deficiency syndromes
24SCLE Typically photosensitive Lesions confined to sun-exposed skin Regular association with anti-Ro antibody (SS-A)Subacute cutaneous LE (papulosquamous pattern).
25Effect of ultraviolet (UV) radiation on tissue response Effect of ultraviolet (UV) radiation on tissue response. UV light causes Ro antigen to move to the cell surface, where they bind to anti-Ro antibodies. Women with anti-Ro antibodies may be asymptomatic or have sicca symptoms, photosensitivity, and/or arthralgias. These women are at increased risk for having babies with 3rd degree heartblock, SCLE, hepatobiliary disease, thrombocytopenia, or some combination of these.
26SCLE Psoriasiform, polycyclic annular lesions Shawl distribution: V neck, upper outer and inner arms.¾ of the patients have arthralgia20% have leukopenia80% have positive ANAAssociated with HLA-DR3-Positive.
27Drugs triggering anti-Ro antibodies and thus lesions of SCLE HCTZNSAIDSDiltiazemGriseofulvinTerbinafineLesions may or may not clear once the medication is discontinued.Subacute cutaneous LE (annular-polycyclic pattern). The annular plaques have an erythematous scaly border, the central area is hypopigmented, and the eruption is confined to the back and hands.
28Subacute cutaneous lupus (SCLE) lesions Subacute cutaneous lupus (SCLE) lesions. There are non-scarring, erythematous, slightly scaly plaques on the upper trunk and arms. Annular plaques with crusted margins.
29The lesions on the hands conform to the typical distribution of lupus lesions, sparing the knuckles.
30SCLE displays a superficial and deep perivascular infiltrate of lymphocytes with interface changes at the epidermis.
31Neonatal LE Annular scaling erythematous macules and plaques Appear on head and extremitiesFirst few months of life in babies born to mothers with LE, RA, or other connective tissue diseaseResolve spontaneously by 6 month of ageHALF of the patients have associated congenital heart block, usually 3rd degree
32Neonatal LE Lesions histologically identical to SCLE Almost 100% have anti-Ro antibodiesUnlike adult SCLE, lesions have predilection for the face, especially periorbital regionLesions typically resolve without scarringOther internal findingsHepatobiliary diseaseThrombocytopenia
33Neonatal lupus. Annular erythematous plaques with a slight scale usually appear on the head slightly after birth. Sun exposed areas of the arms and trunk may also be involved. Telangiectasia is often prominent. Skin lesions resolve with time.
34Erythematous, atrophic, annular plaques distributed on forehead, periorbital ridge, and temples, with no associated scale or telangiectasia.
35Acute Cutaneous LE Characteristic butterfly facial erythema May last from days to several weeksBullous lesion occur as single or grouped vesicle or bullaeSubepidermal bulla containing neutrophils.HLA-DR2 positiveMinute telangiectasias appear in time on the face or elsewhere and commonly appear about the nail folds.Rowell Syndrome: EM-like lesion dominant in LE
42Systemic 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.
43Systemic Manifestation. CNS involvementIdiopathic thrombocytopenic purpura.Sjogren’s syndromeMixed with dermatomyositis
44Treatment 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!Benefits of discontinuing smoking related to the fact that smoking may make antimalarial therapy less effective.
48Dermatomyositis Poikiloderma Gratton's sign - flat-topped violaceous papulesHeliotrope - reddish -purple flush around the eyesOver knuckle streak erythemaShawl patternBimodal distributionCalcinosis Cutis may occur in over half of the children with DMAssociated with Malignancy in 10-50% of adultsPoikiloderma most important diagnostic feature of the cutaneous eruption of dermatomyositis. Poikiloderma violaceous in dermatomyositis and red in SLE
50Dermatomyositis Symmetrical muscle weakness assoc c malignant neoplasm when over 40periungual telangiectasiaPrednisone 1mg/kg with slow taperSunscreen, antimalarialMechanics hand: hyperkeratosis, fissuring, scaling involvement in the palm of the hand.
51Muscle involvement Symmetrical muscle weakness Unable to raise arms to comb their hairCardiac involvement with cardiac failure in terminal phaseAmyopathic dermatomyositis or dermatomyositis sine myositis: DM without muscle changes
52Childhood DM Brunsting type Banker type Slow course Progressive weaknessCalcinosisSteroid responsivenessBanker typeVasculitis of muscles and GI tractRapid onsetSevere weaknessSteroid unresponsiveness
62Sclerodermacharacterized by symmetric thickening, tightening, and induration of the skin of the fingers and the skinThese changes may affect the entire extremity, face, neck, and trunk (thorax and abdomen).Occurs in localized and systemic forms
63Localized MorpheaSmooth, hard, somewhat depressed, yellowish white, or ivory-colored lesions.Common on the trunkMargins surrounded by light violaceous zone or by telangiectasias.Resemble pigskin (prominent follicular orifices)Slowly involute over a 3-5 year period.
64Generalized Morphea Widespread hard indurated plaques. No systemic involvementPatient appear young because of the firmness of the skin.Resolution less likely than the localized version.
65Early inflammatory plaque type morphea of the trunk
67Atrophoderma of Pasani and Pierini Reduction of thickness of dermal connective tissueUpperback and lumbar sacral areaBenign course, usually resolve after few months or few years.No effect treatmentVariant of morphea.
68Atrophoderma of Pasini and Pierini Atrophoderma of Pasini and Pierini. A Multiple depressed, slightly hyperpigmented patches on the back. B Coalescent hyperpigmented patches on the abdomen.
69Linear Scleroderma Linear lesions extend to length of arms or leg Begin first decade of lifeMay also occur parasagitally down the forehead, known as en coup de sabreParry-Romberg syndrome: progressive facial hemiatrophy, epilepsy, exophalmos, and alopecia, maybe a form of linear scleroderma.
73CREST Syndrome AKA Thibierge-Weissenbach Syndrome. Systemic sclerosis may be limited to the hands, and is called acroslerosis.Not as severe as PSSANA shows anticentromere antibody, and is highly specific.Most favorable diagnosis
75Calcinosis cutis of the thumb in a patient with scleroderma
76Progressive Systemic Sclerosis Raynaud’s is the first manifestation of PSS most of the time and is eventually nearly always presentRound 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
77Progressive Systemic Sclerosis 75% have dilated nail fold capillary loopsEsophageal involvement in 90% of patientsPulmonary fibrosisCardiac involvementArticular pain, swelling, polyarthritis.
78Prognosis Skin involvement after 1 year of diagnosis: Group I – sclerodactyly alone – 71% 10 year survival rateGroup II - Skin stiffness above metacarpal-phalangeal joints but not involving trunk – 58% survival rate.Group III – truncal involvement – 21% survival.
79LAB FindingTopoisomerase 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 fibrosisAnticentromere antibodies are present in about 60-90% of patients with limited disease and 10-15% with diffuse disease.
80Histology 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.
81Treatment Symptomatic tx Treatment aimed at minimizing complications Regular massage, warmth, and protection from traumaNo smoking
82There is a dense sclerosis of the dermis with decreased adnexal structures, and ‘trapping’ of remaining adnexal structures encased by collagen. Sparse perivascular lymphocytes are present.
83Treatment of morphea and lichen sclerosus Treatment of morphea and lichen sclerosus. +++ Highly effective; ++,effective +, moderately effective; 0, low efficacy or ineffective. 1, double-blind controlled trials; 2, clinical trial; 3, anecdotal report.
84Eosinophilic 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 groupsExcellent response to corticosteroid.
85Comparison of deep morphea and eosinophilic fasciitis 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.
86HistologyPatchy lymphocytic and plasma cell infilrate in the fascia and subfacial muscle and great thickening, times normal of the fascia.
87In the septae of the subcutis and fascia there is fibrosis and numerous inflammatory cells, including lymphocytes, histiocytes, and plasma cells. No eosinophils were found.Comments:A complete blood count demonstrating an eosinophilia and tissue eosinophilia on skin and fascial biopsy are not a prerequisite for the diagnosis of eosinophilic fasciitis. These histologic findings are consistent with the diagnosis.
88Mixed Connective Tissue Disease Mixed features of scleroderma, SLE, and dermatomyositisIgG deposition in speckled (particulate) pattern in epidermal nuclei of normal skin on DIF is a distinctive finding in MCTDTreatment with daily dose of prednisone 1mg/kg shows good improvement.Most patients have anti-U1RNP antibodies
89Sjogren’s Syndrome AKA Sicca syndrome Triad of keratoconjunctivitis sicca, xerostomia, and rheumatoid arthritis.RF is usually positiveElevated C-reactive Protein, IgG, IgA, and IgM80% has anti-Ro/SSA antibody.>50% have anti-La/SSB antobodiesOnly symptomatic treatment available.Labial salivary gland biopsy most definitive test
90Schirmer test Assesses lacrimal gland function Whatman paper wick folded over eyelid for 5 minutes<5mm tear film migration = lacrimal gland dysfunction
91Rheumatoid Nodules 20-30% of RA patients Subcutaneous nodules Found anywhere on the bodyHistologically shows dense foci of fibrinoid necrosis surrounded by histiocytes in palisaded arrangement.
93Relapsing 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.
94Erythema and swelling of the ear with sparing of the earlobe (no cartilage)