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1. Connective Tissue
Diseases
Dr Gaurab Acharjee

2. Contents
• Lupus erythematosus (DLE/SCLE/SLE)
• Scleroderma (morphea/systemic sclerosis)
• Dermatomyositis/polymyositis
• Rheumatoid arthritis
• Sjogren’s syndrome
• Mixed connective tissue disease
• Antiphospholipid antibody syndrome

3. Lupus Erythematosus (LE)- Types
• Cutaneous lupus erythematosus is classified into three subtypes:
− Acute cutaneous lupus erythematosus (ACLE):
• Malar rash, morbilliform rash, bullous lesions
− Subacute cutaneous lupus erythematosus (SCLE):
• Annular, papulosquamous
− Chronic cutaneous lupus erythematosus (CCLE):
• Discoid lupus erythematosus

4. Pathogenesis of Cutaneous LE
• Genetic Factors - HLA susceptibility
• Environmental triggers–
− UV exposure induces cytokine release and apoptosis
• Immunologic factors–
− Malfunction of T regulatory cells (T reg)
− Role of IL-18

5. Acute Cutaneous LE
• Localised ACLE–
− Characteristic butterfly facial rash
• Generalised ACLE-
− Widespread maculopapular rash in a photo-distributed pattern

6. Subacute Cutaneous LE
• Non-scarring; papulosquamous/annular polycyclic lesions
• Vesiculation, crusting, hypopigmentation, telangiectasia, alopecia,
photosensitivity, Raynaud’s phenomenon
• Sites: Above waist, neck, arms
• Systemic involvement 35%
• ANA, anti-Ro, anti-La

7. Chronic: Discoid Lupus Erythematosus (DLE)
• DLE is a relatively benign disorder of the skin, characterized by well
defined, reddish, scaly patches which tend to heal with atrophy,
scarring and pigmentary changes
• The histology is characteristic
• Female: Male - 2:1
• Onset - Second-fourth decade of life
• Family history: 4%
• Genetic factors - HLA B7, B8

8. Discoid Rash

9. Diagnosis
• Histopathology:
− Epidermal atrophy, basal layer liquefaction, lymphocytic dermal
infiltrate and ‘civatte bodies’
• Differential diagnosis:
− Polymorphous light eruption, morphea, lichen planus, lupus
vulgaris, sarcoidosis

10. • Definition:
− A systemic disease with immunopathological abnormalities
affecting various organs particularly the skin, joints and
vasculature
• Females >males
• Onset: Early adult life
Systemic LE

11. Clinical Features
• Fever (52%), lymphadenopathy
• Arthritis (84%) and arthralgia
• Cutaneous lesions: Specific and non -specific
• Raynaud’s phenomenon
• Renal - nephritis or as nephrotic syndrome
• Lung-pleural effusion, alveolitis, interstitial lung disease
• Cardiac-pericardial effusion, myocardial infarction, Libman-Sacks
endocarditis

12. Clinical Features
• CNS involvement: Migraine, epilepsy, neuropathy
• GIT and hepatic involvement: Vasculitis of gut, ascites, pancreatitis,
autoimmune hepatitis
• Splenomegaly, hepatitis, cirrhosis
• Hematologic: Anemia, leukopenia, thrombocytopenia
• Ocular: Conjunctivitis, episcleritis, retinal vasculitis

13. Cutaneous Lesions
• LE specific
− ACLE – Malar rash
− SCLE – Annular, psoriasiform
− CCLE – Plaque
− Lupus panniculitis
− Hypertrophic
− Tumid CCLE
− Chilblain CCLE
− Mucosal CCLE

14. Malar rash Oral ulcer
Cutaneous Lesions

15. Investigations
• CBC: Anemia, leukopenia, thrombocytopenia
• ESR: Raised
• Urine analysis, BUN, S. creatinine
• False positive VDRL and RA factor
• LE cell test
• ANA
• Anti-DNA, anti-Smith, anti-histone, cryoglobulins, serum complement
levels
• DIF – Lupus band test

16. American College of Rheumatology, ACR
Criteria
• Malar rash
• Discoid rash
• Photosensitivity
• Oral ulcers
• Non–erosive arthritis
• Serositis: Pleurisy or pericarditis
• Renal disorder: Persistent proteinuria (>0.5g/day) or cellular casts
• Neurological disorders: Seizures or psychosis
Contd…

17. American College of Rheumatology, ACR
Criteria
• Hematological disorders - Hemolytic anemia or leukopenia
(<4000/mm3) or lymphopenia (<1500/mm3) or thrombocytopenia
(<1,00,000/mm3)
• Immunological disorder - LE cells, or anti-dsDNA antibody or anti
Smith antibody or false positive VDRL
• Antinuclear antibodies
4 or more criteria are required for definitive diagnosis

18. Treatment
• Mild disease
− NSAIDs, topical therapy, antimalarials
• Severe disease
− Systemic steroids
− Steroid sparing immunosuppressants- Azathioprine,
cyclophosphamide, mycophenolate mofetil
− Biologics - Rituximab-monoclonal ab targeting CD20 receptor
protein on surface of B cells-mainly for arthritis and proteinuria

19. Morphea
• Definition:
− Sclerosis confined to the skin, localised or generalized is termed as
‘morphea’
− Female: Male - 3:1
− Onset: 20-40 years;
− Precipitating factors: Trauma, vaccination, radiotherapy, hormonal
factors, borrelia infection, measles, silicone implants

20. Types of Morphea
• Plaque type - Morphea en plaque, guttate morphea, keloid (nodular)
morphea, atrophoderma of Pasini and Pierini
• Generalised morphea
• Bullous morphea
• Linear morphea - Linear type, en coup de sabre, progressive
hemifacial atrophy
• Deep morphea - Subcutaneous morphea, eosinophilic fasciitis,
morphea profundus, disabling pansclerotic morphea

21. Clinical Features
• Plaque type –
− Round or oval indurated plaques with lilac border
− Heals slowly with residual hyperpigmentation
− Multiple, asymmetrical distribution
− Sites: Trunk, limbs, face
• Linear morphea -
− Plaques of morphea in linear arrangement mainly on limbs
− Type on frontoparietal region - en coup de sabre

22. En-Coup-de-Sabre

23. Treatment
• Triamcinolone acetonide, 10-40 mg/ml intralesional injection
• Penicillamine: 300-600 mgs/day
• Diphenylhydantoin
• Systemic steroids
• Cyclosporine
• Topical vit. D3 analogues
• Topical tacrolimus
• Phototherapy, plasmapheresis, physiotherapy, plastic surgery

24. Systemic Sclerosis
• Systemic sclerosis is a multisystem autoimmune disorder
characterized by vascular abnormalities, connective tissue sclerosis
and atrophy
• Females: Males - 5.2:1
• Onset: Fourth decade
• Aetiology and pathogenesis: Complex autoimmune disease
characterised by immune activation, fibrosis of skin and obliterative
vasculopathy

25. Classification According to Skin Sclerosis
• Limited cutaneous scleroderma - Skin sclerosis of fingers
(sclerodactyly) with or without mild sclerosis of face, neck and
armpits
• Diffuse cutaneous scleroderma - Diffuse and truncal sclerosis
• Immediate cutaneous scleroderma - Sclerosis of upper and lower
limbs, neck and face without truncal involvement
• Sine scleroderma SSc - Absence of cutaneous sclerosis with typical
visceral organ involvement, capillaroscopy changes and serum
autoantibodies

26. Cutaneous Features
• Raynaud’s phenomenon
• ‘Hide-bound’ skin
• Classical scleroderma facies- “mask-like” face, pinched or beak-like
appearance of nose, radial furrows around the mouth and thinning of
the upper lip
• Pigmentation – mottled or hyperpigmentation
• Swelling of hands and joints, atrophy
• Finger and leg ulcers, digital gangrene, stellate scars
• Nail fold telangiectasias
• Calcinosis

27. Pitted scars
Classical scleroderma facies
Features of Systemic Sclerosis

28. Systemic Features
• Gastrointestinal and hepatic –
− Oesophageal dysfunction, malabsorption, primary biliary cirrhosis,
autoimmune hepatitis
• Arthritis, tendon friction rubs
• Renal-scleroderma renal crisis (most severe)
• Lung - Interstitial lung disease, pulmonary hypertension
• Cardiac- Myocardial disease, pericardial involvement
• Muscle- SSc associated myopathy more common in diffuse SSc

29. Diagnosis
• 2013 ACR/EULAR criteria –
− Skin thickening of the fingers extending proximal to MCP it is sufficient to
diagnose the patient as SSc
− If this is not present seven other features apply with for varying weights for
each -
• Skin thickening of fingers
• Finger tip lesions
• Telangiectasia
• Abnormal nail fold capillaries
• Interstitial lung disease or pulmonary artery hypertension
• Raynaud’s phenomenon
• SSc related autoantibodies (anticentromere, anti-topoisomerase, anti Rnp-
3)

30. Investigations
• Serology: ANA, anticentromere antibodies, anti-Scl 70 antibody
• Pulmonary function test: Detect fibrotic changes
• Histopathology: Hyalinization and homogenisation of collagen, dermal
lymphocytic infiltrate
• ECG: To detect rhythm and conduction abnormalities
• ECHO: Detect pulmonary artery hypertension
• GI involvement: Oesophageal manometry, endoscopy, barium studies
Contd…

31. Treatment
• Use of gloves
• For Raynaud's - Nifedipine (mild cases), sildenafil, iloprost, low
molecular weight dextran
• Corticosteroids
• Immunosuppressants: Methotrexate, cyclophosphamide
• Penicillamine, colchicine, interferons
• Symptomatic treatment for pulmonary, cardiac, renal and GIT
symptoms

32. Dermatomyositis
• An idiopathic inflammatory myopathy characterised by muscle
weakness and cutaneous eruption
• Females >males
• Bimodal peak during childhood and then between 50-70 years
• Aetiology
• HLA-B8, DRB1*0301, DQA1*0501, DQA1 *0301
• Infections - Gr A beta haemolytic streptococci, toxoplasma, coxsackie
• UV radiation exposure
• Drugs- D penicillamine, tamoxifen, INH, penicillin

33. Cutaneous Features
• Pathognomic skin manifestation – Gottron’s papules and Gottron’s sign
• Gottron’s papules - violaceous papules overlying the dorsal
interphalangeal and metacarpophalangeal joints, elbows and knees
• Gottron’s sign - Erythematous or violaceous erythema with or without
oedema
• Characteristic skin lesions - Heliotrope erythema and macular
violaceous erythema over the deltoids, posterior shoulders, nape of
neck, upper chest (V sign), forehead and dorsa of hands
• Cutaneous calcinosis more common in JDM, 40-75% cases

34. Heliotrope Gottron’s papules

35. Systemic Manifestations
• Muscle: Progressive symmetric proximal myopathy; pharyngeal and
respiratory muscles may be involved
• Joints: Non erosive arthritis, usually an early manifestation
• Pulmonary: Aspiration pneumonia, interstitial lung disease,
hypoventilation
• Cardiac: Arrythmia, conduction abnormalities myocarditis
• Gastrointestinal: Dysphagia, oesophageal reflux

36. Criteria for Diagnosis (Bohan and Peter)
• Symmetric muscle weakness
• Elevation of skeletal muscle enzymes
• Abnormal EMG results
• Muscle biopsy results
• Typical rash of DM
Definite diagnosis: Characteristic skin rash + ¾ remaining criteria

37. Investigations
• Muscle enzymes: CK, SGOT, SGPT, LDH, S. aldolase
• CK - MM fraction most specific for skeletal muscle
• Muscle biopsy - definitive diagnosis
• EMG
• MRI - may detect subclinical muscle involvement
• Serology: ANA, anti Jo-1, anti-Mi2

38. Treatment
• Corticosteroids
• Immunosuppressants: Methotrexate, mycophenolate mofetil
cyclophosphamide, azathioprine
• Methotrexate considered first choice among adjuvants
• IVIg - refractory cases
• Rituximab
• Exercise and physical therapy
• Cutaneous lesions: Sunscreens, hydroxychloroquine
• Calcinosis: Alendronate, diltiazem, excision of large lesions

39. Mixed Connective Tissue Disease
• Affects predominantly females
• Features of SLE, systemic sclerosis, dermatomyositis, polymyositis
• Specific antibody to U1-RNP
• Raynaud’s phenomenon, arthritis, arthralgia, sausage shaped fingers,
swelling of hands, photosensitivity, SCLE like rash
• Abnormal oesophageal motility, impaired pulmonary diffusing
capacity, myositis, aseptic meningitis, psychosis, trigeminal
neuropathy

40. Sjogren's Syndrome
• Xerostomia with keratoconjunctivitis sicca
• Cutaneous features:
− Xerosis, generalised pruritus, loss of sweating, diffuse alopecia,
recurrent annular erythema
− Raynaud’s phenomenon, non-thromobocytopenic purpura,
urticarial vasculitis, necrotising vasculitis, splinter haemorrhages,
gangrene

41. Cutaneous Manifestations of Rheumatoid
Arthritis
• Specific manifestations:
− Rheumatoid nodules - Most frequent extra-articular manifestation
− Granulomatous dermatitis - Linear erythematous to violaceous
subcutaneous bands in axilla, trunk, inner aspect of thighs
− Rheumatoid vasculitis - Ulcers, digital infarcts, nail fold infarcts
(Bywater's lesions)
− Pyoderma gangrenosum
− Felty's syndrome
− Juvenile onset RA
• Non specific manifestations:
− Palmar erythema, sclerodactyly like changes, periungual erythema,
splinter haemorrhages, bluish discoloration of fingers

42. Antiphospholipid Antibody Syndrome
• Primary and secondary
• Secondary causes include - autoimmune connective tissue diseases,
Takayasu’s arteritis, bacterial and viral infections, malignancies,
dialysis in renal failure
• Approximately 40% have cutaneous manifestations
• Livedo reticularis most common
• Others - necrotising vasculitis, thrombophlebitis, cutaneous ulcers,
gangrene, necrosis, purpura, erythematous macules, ecchymoses,
painful skin nodules, anetoderma, atrophie - blanche like lesions,
subungual splinter haemorrhages

43. Thank You