Connective Tissue Diseases - Scleroderma

How is the GI system affected?

(dysphagia and the esophagus can be affected) - *Esophagus is the M/C organ affected (80% or more)* >> Fibrosis of smooth muscle in the distal esophagus -> decreased peristalsis and dysphagia with heartburn (reflux type symptoms) - May also affect small and large intestines >> Later diarrhea, constipation, diverticular ds (motility and function is affected)

The M/C presenting sign is:

*Raynaud's Phenomenon* - Vasospasm often caused by cold, cigs, stress - Coldness, numbness and white color to fingers and toes -> cyanosis -> painful red hyperemia (95%) - sclerodactyly (disfiguring finger condition)

Renal involvement

*Scleroderma Renal Crisis* (SRC) - new onset of extremely high, arterial BP or rapidly *progressive oliguric RF*

Prognosis

*not a death sentence* - 70-80% survive 10 years after diagnosis - but overall very *difficult to dx and txt* since in the really stages the sxs are very non-specific

Manage the symptoms

- *ACE inhibitors* at first sign of HTN - *PPI* for GERD sx + lifestyle modifications such as elevation of HOB(head of bed), small frequent meals, reduce caffeine - Skin- *emollients creams, massages* (to release the tension) - Raynaud's >> keep hands and feet very warm >>> *Nifedipine* (blood flow) and *topical nitroglycerin*(doesn't work for everyone) - Digital care (due to ulcerations) >> *Duoderm dressings*, *topical antibiotics* for ulcers - Joint paints >> NSAIDs

Diagnosis for scleroderma

- *ANA is positive* (in 95% of cases) - *Topoisomerase I antibody* (in 20-30% with *diffuse*) - w/ more pulmonary fibrosis issues *this AB is ONLY IN SCLERODERMA* - *Anticentromere Ab* (60-90% with *limited*) (10-15% with diffuse)

Pulmonary involvement

- *Alveolitis* leading to pulmonary fibrosis is a common complication of scleroderma (M/C in diffuse scleroderma) - Pulm HTN (M/C in limited scleroderma)

Localized Scleroderma

- *Morphea* (patches of thickened skin) - Linear (thickened skin tethered to underlying muscle and bone) - Scleroderma en coup de sabre ("cut of the saber," linear scleroderma of the head and face only)

Clinical presentation

- *Not an easy diagnosis* - unless the skin changes are severe - vague complaints that are seen in a lot of your AI dz >> Severe fatigue, malaise, and some weight loss are very common early in the disease

Epidemiology of scleroderma

- *Women* outnumber men by approximately 5:1 - Peaks at age 40 - 50 years (later than lupus) - *Blacks* have a slightly higher risk of getting scleroderma and at a younger age (also it will be more diffuse and severe than whites)

Later presentations of skin involvement

- *swollen "edematous" phase*, and sometimes severely itchy and dysesthetic to the touch (pain to touch)

How is the Musculoskeletal affected?

- Arthralgias and myalgia (more so from the skin tightening than the actual arthritis/joints infected) >> May *progress to fibrosis of tendons* esp around *wrists and ankles* (friction rubs palpated over affected joints) - May indicated severe internal organ fibrosis if friction rubs are notes (the dz has progressed and now internal organs are being damaged too)

Monitoring

- BP (home monitoring and frequent check ups) - Signs and symptoms of skin and internal organ damage - PFTs (due to lung fibrosis involvement) - EKG, echocardiogram - SMA7 (chemistry panel to monitor the internal organ fxn)

Cause of Scleroderma

- Extensive fibrosis which is initiated by an unknown trigger (environmental?) in a genetically susceptible person - This activates/triggers the whole immune system --> T cells, B cells, macrophages --> *cytokines* that cause damage and activation of endothelial cells in the blood vessel linings (narrowing of blood vessels) --> activating *fibroblasts* --> *uncontrolled collagen synthesis* --> *fibrosis* in the blood vessels, dermis and the organs.

Cardiac Involvement

- Fibrosis may involve pericardium, myocardium, pulmonary blood vessels >> possibly leading to cor pulmonale. > Late finding and subtle with *severe prognosis* > S/S: DOE, palpitations and CP - 2D echo (to see if any changes to the heart)

Initial presentation of skin involvement:

- Initially starts with bilateral, nonedematous, thickening and tightening of the skin over the fingers >> This can progressively involve the hands, limbs, and trunk and can occur over weeks to months

how is the skin after months/years?

- Months to years >> tight *hard* skin bound to subcut tissue, restricted movement of finger joints (so much collagen - causes tightening of the skin- gets stuck to underlying tissue and gets stuck) - Many years >> atrophic skin, digital ulcerations, flexion contractures (compromising blood supply - can't move properly)

Alveolitis continued -

- Most common in diffuse scleroderma with onset in first 3 years for most its - Symptoms: range from cough and SOB on exertion -> SOB at rest with need for continuous O2

Other Clinical Manifestations

- Neuritis, carpal tunnel syndrome - Hypothyroidism (autoimmune component) - Sjogren's syndrome - Vaginal dryness and dyspareunia - Calcinosis >>> knees, elbows later in limited type PIC - Sclerodactyly- loss of digital pad and ulcerations of fingertips - (Resorption of distal phalanges in severe, chronic vasospastic ischemia)

Some examples of external stimuli (didn't say this- bottom of slide)

- cold (in the case of Raynaud's phenomenon), - toxic substances, such as organic solvents and silica dust, - organ transplantation. (Transplantation can result in graft-vs-host disease, which can have scleroderma-like symptoms) (none have been shown to be the singular cause)

Hallmark of scleroderma

- excessive collagen deposited around capillaries, small vessels and in affected tissues (like the *skin*, lungs, kidneys, and esophagus)

Pathogenesis of scleroderma

-There is an interrelationship among immune, vascular, endothelial, fibroblast, and genetic processes that results in the manifestations of scleroderma - If there is a genetic background and an external stimulus, the immune system is activated, resulting in vascular injury, fibroblast proliferation, and collagen deposition in the skin and, often, internal organs

Diffuse Scleroderma

extensive skin thickening *proximal to the elbows and knees along with internal organ involvement* (intestines and stomach affected)

Limited scleroderma involves..

face and distal limbs, *but NOT the trunk* - Telangectasias on the face, lips, tongue and hands - Calcinosis

Scleroderma

is an autoimmune connective-tissue disease

Diffuse scleroderma involves..

proximal and distal extremities *as well as the trunk* - (Rapid progression of skin involvement has a more severe prognosis with severe internal organ involvement)

Scleroderma en coup de sabre

seen with localized scleroderma

Facial changes

stiff drawn in b/c skin is so tight

Other tests- (b/c of the dif s/e that can result from scleroderma)

CXR CT chest PFTs UA SMA7 EKG 2D echo Upper GI series (she didn't read these)

what are we worried about with scleroderma

Causes of Mortality are due to >>> - pulmonary disease (due to fibrosis) - Used to be renal crisis before ACE-I

Who is at the highest risk for developing SRC

Patients with *diffuse cutaneous scleroderma* with skin thickening on the proximal extremities or the trunk are in highest danger of developing SRC at 20% to 25% txt fast/quick w/ ACE-I

Treatment

Refer to rheumatologist *No FDA approved drugs for scleroderma* (NO specific drug is being used specifically for scleroderma): - *D penicillamine, methotrexate* are immunosuppressive drugs which may help skin thickening - *Cyclophosphamide* may be helpful for pulmonary fibrosis - *Prostacyclin analogs* and *endothelin receptor antagonists* in clinical trials for pulmonary HTN - Update new drug approved for pulmonary HTN called *iloprost* (Ventavis) - CCBs - are thought to help - to relax blood vessels - *TRIAL AND ERROR* for what helps these pt. - Antifibrotic drugs?

tell pt to

STOP SMOKING - its affecting their circulation and putting them at higher risks (esp for raynauds and ulcerations)

Sclerodactyly

Skin looks super tight and ulcerations are seen

2 types of scleroderma

Systemic (limited or diffuse) Localized

Limited scleroderma

also called CREST: - Calcinoshs (Ca2+ deposits in the skin tissue) - Raynaud's (cold exposure-compromised blood supply) - Esophageal dysfunction (trouble swallowing) - Sclerodactyly (tightening of skin- can't extend fingers - loss of finger pads) - Telangiectasias (curly blood vessels seen in skin)