Connective Tissue Disease, Vasculitis and Related Disorders

Connective tissue disease triggers

1- Unknown (usually)

2- Sunlight

3- Infection

4- medication

Vasculitis

Vasculitis pathophysiology

- Complex and poorly characterized.

- Antibodies or immune complex-mediated.

- Immune complex deposition at blood vessel wall >> Inflammation >>

Complement activation & inflammatory mediators release >> vasodilatation &

polymorph accumulation >> Leakage so RBC extravasation >> occlusion of blood

vessels >> Ischemia.

Bullous vasculitis with necrosis

Vasculitis clinical presentation:

• General malaise

• Fever

• Abdominal pain

• Arthropathy

• Skin lesions:

- Non-blanching

- Erythematous macular, palpable purpura

- Can become blistering, ulcerated, and necrotic.

- Transient or last for weeks.

- Painful and unpleasant.

- M.c Location: Lower Limbs

Polyarteritis Nodosa Clinical Presentation:

General:

• General malaise

• Fever

• Weight loss

• Weakness

• Arthralgia

• Neuropathies

• Renal involvement (can cause renal failure)

Cutaneous:

• Livedo reticularis (subtle lacy mottled pattern)

• Purpura

• Tender subcutaneous nodule

• Ulceration

• Necrosis

• M.C location: Lower limbs.

Retiform Purpura PAN

Livedo reticularis PAN

PAN Retiform Purpura

PSN Retiform Purpura

PAN Ulceration Necrosis

PAN investigations

1. Angiography

2. Tissue biopsy ( skin, sural nerve, muscle )

PAN management

1. Corticosteroids (oral)

2. Cyclophosphamide in severe cases.

Henoch – Schönlein purpura pathophysiology

Deposition of IgA, complement and immune complexes in small vessels

(arterioles, capillaries , venules) leading to systemic vasculitis.

• Skin, kidney, GI tract, and joints are mainly affected.

Henoch – Schönlein purpura Clinical Presentation:

• Cutaneous:

• Vasculitic rash on the buttocks and lower

legs

• Might be associated with edema of

scrotum/hands/ears

• GI: Abdominal pain, Vomiting

• Joint pains in the knees/ankles

• Hematuria.

Henoch – Schönlein purpura

Henoch – Schönlein purpura

Henoch – Schönlein purpura

Henoch – Schönlein purpura

Henoch – Schönlein purpura Investigations:

1. Hx and P/E

2. Skin biopsy:

-Deposition of IgA on immunofluorescence (support the diagnosis).

Henoch – Schönlein purpura management

• Usually supportive (recovery in weeks)

• Systemic corticosteroids:

-If persistent disease

-Can treat skin, GI, and arthritis symptoms

-Don’t prevent or treat renal disease

Management of cutaneous vasculitis

• Treat any underlying causes.

• Support hosiery should be used and the leg elevated on sitting.

• For mild to moderate cutaneous involvement:

-Potent topical steroids can be applied to the affected skin.

• In severe cases:

-Systemic corticosteroid

-Anticoagulation with warfarin or heparin.

• In persistent cases:

-Alternative immunosuppressants (Methotrexate or Azathioprine) may be

needed.

Raynaud’s phenomenon associated with

Raynaud’s disease, systemic sclerosis, mixed connective tissue disease, SLE, and Cryoglobulinemia.

Raynaud’s phenomenon types

1. Primary: Symmetric, before 30 years old, no skin manifestations, idiopathic.

2. Secondary: Asymmetric, ANA can be +ve, digital ulcerations can occur.

Raynaud’s phenomenon Symptoms:

1- Change in color after cold exposure:

White (Vasospasm) >> Blue (Cyanosis) >> Red (hyperemia).

2- Pain

3- Numbness

• The condition most frequently affects the finger in a symmetrical pattern

• Can also affect toes, nose, and ears.

Raynaud’s phenomenon

Raynaud’s phenomenon

Raynaud’s phenomenon

Raynaud’s phenomenon Investigations:

1- Full blood count

2- LFT and KFT

3- Coagulation profile

4- Thyroid function

5- Serum glucose

6- Creatinine kinase

7- Hepatitis serology

8- Antinuclear antibodies

Raynaud’s phenomenon management

1- Keeping peripheries warm

2- Nifedipine

3- Iloprost (Prostacycline Analogue)

Systemic sclerosis (SSc)

• Excessive sclerosis (i.e. collagen deposition and fibrosis) of

the subcutaneous tissues in the fingers and toes as well as

around the mouth (scleroderma), with similar changes

affecting the internal organs, particularly the lung and

kidneys.

• Blood vessels can be affected, leading to:

- Raynaud’s phenomenon (fingers)

- Telangiectasia (mouth and fingers)

Systemic sclerosis (SSc) classification:

1- Limited systemic sclerosis(lSSc):

2- Disseminated systemic sclerosis (dSSc):

3- Undifferentiated connective tissue disease

4- CREST syndrome

Limited systemic sclerosis(lSSc):

• Raynaud starts many years before

• Anti-centromere antibody

• Skin sclerosis distally does not cross the

elbows and knees

• Slowly progressing

• CREST is an example

Disseminated systemic sclerosis (dSSc):

• Raynaud starts 1-2 years before

• Antibodies ANA, Scl-70 (anti

topoisomerase)

• Sclerosis crosses elbows and knees

• Fast progress with internal organs

involvement ( heart, kidneys, lungs)

Raynaud’s and Telangiectasia associated with SSc

Systemic sclerosis (SSc) Clinical Features:

1- Raynaud’s phenomenon

2- Telangiectasia (mouth and finger )

3- Tethering of skin on the fingers/toes

which become very tight with a

waxy appearance and considerable

limitation of movement.

Tethering of skin on the fingers associated with SSc

SSc Diagnosis:

1- ANA ( 90% of patients with SSc will have at least one +ve ANA)

2- CRP / ESR ( raised)

3- High-resolution CT scan of the lung (thickening of the alveolar walls)

4- PFT (impaired ventilation – perfusion)

5- Skin biopsy (fibrotic changes seen in histology )

Morphaea associated with SSc

Benign form of localized systemic sclerosis in

which there is localized sclerosis with very slight

inflammation.

Morphaea stages

- Early stages: Dusky appearance of skin.

- Late stages: Discolored and Firm skin.

Localized morphea in the frontoparietal area is associated with alopecia and sunken groove of firm sclerotic skin.

CREST syndrome Symptoms:

• Calcinosis Cutis: Calcium deposits in the

skin are seen as chalky white material

which can be painful

• Raynaud’s phenomenon: First complaint

• Esophageal Dysmotility

• Sclerodactyly: Thickening of the skin of

the digit

• Telangiectasia: first seen in the face

CREST syndrome

CREST syndrome Management:

• Psychological support

• Patients should keep themselves warm

• Calcium-channel blockers

• Prostaglandins/prostacyclin analogue.

• Calcitriol (for sclerodactyly)

• Pulsed dye laser (for telangiectasia)

CREST syndrome investigations

• FBC (Full Blood Count)

• ANA

• Anticentromere antibodies

• Scl-70

Lichen Sclerosus pathophysiology

Unknown, but in early lesions there is an infiltrate of lymphocytes with CD3,

CD4, CD8, and CD68 markers.

Lichen Sclerosus

Lichen Sclerosus Clinical Features:

• Well-demarcated atrophic patches and plaques

with a distinctive ivory-white color.

• Fibrosis of the underlying tissues with associated

loss of normal genital architecture

• Frequently affects the vulva and perineum, but

may also affect the penis and extragenital skin.

• Children: Acute, resolves

• Adults: chronic, rarely associated with the

development of squamous cell carcinoma (SCC).

Lichen Sclerosus Treatment:

• Intermittent potent topical steroids, which usually

control itching.

• If pruritus is not controlled by potent topical

steroids or soreness develops, you have to rule

out the development of SCC.

Lichen Sclerosus

Lichen Planus Histological features:

Characterized by a band of lymphocytes attacking the basal keratinocytes which

result in edema, subepidermal clefts, and death of some keratinocytes

Lichen Planus

Lichen Planus wickham striae

Lichen Planus Clinical features:

• Itchy eruption consisting of shiny purple-colored flat-topped papules (6 Ps: Pruritic polygonal purple planar papules and plaques)

• Appear on the wrists and ankles.

• White lines called Wickham’s striae may appear on the surface of the lesions at any site

• Lesions may appear in clusters or in linear scratches/surgical scars (Koebner phenomenon)

• In patients with black skin, LP may be very hypertrophic and heal with marked post-inflammatory hyperpigmentation.

• Mouth (buccal mucosa), and genitals (erosions on labia minora ) may also be involved

• Distinctive linear ridges may affect the nails.

• Scalp lesions are often scaly with marked follicular plugging that may result in scarring alopecia.

• Severe acute lichen planus can manifest as bullous lesions

Lichen Planus

Lichen Planus erosions in mouth-wickham striae

Lichen Planus wickham striae

Lichen Planus sever with bullous lesions

Lichen Planus sever with bullous lesions

Lichen Planus sever with bullous lesions

Lichen Planus

Lichen Planus sever with bullous lesions

Lichen Planus treatment:

• Potent topical steroid applied to the itchy active lesions

• Occlusion of the steroid for hypertrophic lesions.

• Severe lichen planus can be treated with systemic Corticosteroids, mycophenolate mofetil, methotrexate, or azathioprine

Lichenoid drug eruptions Clinical Features:

• Clinically similar to LP

• Lesions are usually more extensive and oral involvement is rare .

• Lesions only resolve very slowly after the drug is stopped, generally taking 1–4 months to settle and usually leaving hyperpigmentation on the skin.

drugs that cause Lichenoid drug eruptions

Antihypertensives, ACE inhibitors, beta-blockers, nifedipine, methyldopa

Clinical variants of lupus erythematosus

• Systemic (SLE)

• Subacute cutaneous lupus

• Discoid Lupus

• Neonatal Lupus

Systemic Lupus erythematosus presentation

• 75% of patients have skin involvement, most commonly an erythematous ‘butterfly’ distribution rash on the face, Photosensitivity, hair loss, and areas of cutaneous vasculitis.

• As the disease progresses the cutaneous manifestations can become extensive.

• Systemic changes include fever, arthritis, and renal involvement, but there may be involvement of a wide range of organs.

Drugs that can trigger Systemic Lupus erythematosus

chlorpromazine, quinine, and isoniazid.

Systemic Lupus erythematosus Tx

• Prednisolone is usually required

• Sometimes immunosuppressant drugs such as azathioprine as well.

Subacute lupus erythematosus (SLE)

Erythematous annular and serpiginous eruption on the skin

(E.N.A (extractable nuclear antigen) test is positive in 60% and anti-cytoplasmic antibodies are present in 80% of patients.)

Discoid lupus erythematosus (DLE)

Well-defined erythematous lesions with atrophy, scaling, and scarring occur on the face, scalp (alopecia, follicular plugging), and occasionally arms.

Discoid lupus erythematosus (DLE)

Discoid lupus erythematosus (DLE)

DLE Tx

• Potent and super-potent topical steroids to limit

scarring

• Hydroxychloroquine 200mg twice daily can be

effective (ask about eye sx, rare ocular toxicity)

Neonatal lupus erythematosus

Skin lesions characterized by annular scaly and inflammatory lesions on the face/scalp.

• Congenital heart block (which may require pacing).

Neonatal lupus erythematosus

Neonatal lupus erythematosus Treatment:

Skin lesions may require topical steroids and sunscreen but usually resolve spontaneously as the level of autoantibody depletes.

Dermatomyositis V sign

Dermatomyositis shawl sign

Dermatomyositis Heliotrope Rash

Dermatomyositis clinical presentation

• Rash on a photosensitive distribution.

• Characterized by a purple hue (heliotrope) on the upper eyelids, cheeks, and forehead.

• The anterior neck and chest rash is a ‘V’ sign while posteriorly is called a shawl sign.

• The dorsal surface of the fingers may be affected by the erythematous eruption and purplish (Gottron’s) papules may predominate over the dorsal finger joints.

• Ragged cuticles and dilated nail-fold capillaries may also be seen.

• There is a variable association with muscle discomfort and weakness, which is mainly in the proximal limbs but bulbar and respiratory muscles may be affected.

• In adults may precede the diagnosis of an underlying tumor (most commonly breast, lung, ovary, or gastrointestinal tract)

Dermatomyositis Gottron’s papules

Dermatomyositis Gottron’s papules

Dermatomyositis Ragged cuticles and dilated nail-fold capillaries

Dermatomyositis Investigations:

• Labs: Creatine phosphokinase (CK), ESR, Anti-Jo-1 antibody.

• Skin and muscle biopsy.

• Electromyography and MRI can help demonstrate myositis.

Dermatomyositis Treatment

• High-dose systemic corticosteroids (60–100mg daily) or pulsed methylprednisolone (1 g daily for 3 days) helps achieve rapid control of symptoms.

• Pulsed cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil.

• Treatment of any underlying malignancy will usually lead to the resolution of these skin signs.

Mixed connective tissue disease (MCTD) Clinical Features:

They usually have Raynaud’s phenomenon, sclerodactyly/swollen hands, arthritis/ arthralgia, Sjogren syndrome, myositis, malaise, oesophageal dysmotility, trigeminal neuralgia, & pulmonary hypertension.

(its a combination of SLE, scleroderma, and myositis)

MCTD Investigations:

Positive antibodies to U1-ribonucleoprotein (RNP) and small nuclear ribonucleoprotein (snRNP)

MCTD Treatment

• NSAIDs are used to reduce pain and inflammation and the newer cyclooxygenase 2

(COX-2) inhibitor celecoxib is increasingly used to help reduced arthritis and myositis.

• Hydroxychloroquine

• For refractory disease low dose of oral corticosteroids and methotrexate