1 Connective tissue diseases???Let me see Introduction Terminology Classification Causes Precautions Connective tissue diseases??? Dr. Hala Helmi A. Hazzaa Associate Professor of Oral Medicine, Peiodontology, Diagnosis & Radiology Al-Azhar University (Girls Branch)

2 Introduction: There are four types of tissues in the human body:The epithelial tissue. The connective tissue. The muscles. The nervous tissue. The connective tissue (CT) is one of the four types of biological tissues that supports, connects, or separates different types of tissues and organs in the body. It develops from the mesoderm.

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5 Connective Tissue Disease (CTD)A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. The four tissue types of human body

6 Classification of CTDsHeritable connective tissue disorders Marfan syndrome Ehlers-Danlos syndrome Osteogenesis imperfecta Autoimmune connective tissue disorders Systemic lupus erythematosus (discussed before with white & red lesions) Rheumatoid arthritis Scleroderma Sjögren's syndrome Mixed connective tissue disease Psoriatic arthritis Acquired connective tissue disorders (e.g.; Scurvy )

7 I) Heritable CTDs

8 Marfan Syndrome (MS) It was firstly described by the pediatrician Antoine Bernard-Jean Marfan. It is a dominant autosomal genetic disorder causing abnormal fibrillin. The genetic disorder leads to mutations in the fibrilin glycoprotein’s gene-1 located in the chromosome 15q21. It affects the elastic fibers of the connective tissue, showing itself in the following systems/organs; the cardiovascular, skeletal, dura mater, ocular, skin, ligaments and lung. No sex predilection. Remember that: The normal fibrilin inhibits the growth of the long bones and elastic fibers, through its tension control the growth of these, because of it, at these structures being altered, an exaggerated bone overgrowth is produced.

9 B (A) Physical Characteristics of MS. The long extremities are evident. (B) Intraoral aspect. Front side. A gingivitis with dental plaque is observed, with severe malocclusion. (C) Lateral incisor are not lining up because of the little transverse development of the maxilla. A C

10 The common oral manifestations in Marfan Syndrome:Deep palate Retrognathia of the maxilla and mandible in 70% of the evaluated patients. A higher caries prevalence in up to 17 years. High prevalence of hypoplasic stains. Radicular deformation and pulp obliteration. High gingival and plaque indices. Severe forms of periodontitis may be seen. High prevalence of temporomandibular joint dysfunction was also reported.

11 Ehlers-Danlos Syndrome (EDS)Ehlers-Danlos syndrome is a rare heriditary collagen disorder. It is genetically transmitted as autosomal dominant disorder. There is a defect in the synthesis of collagen (Type I or III) causes progressive deterioration of collagens, with different EDS types affecting different sites in the body, such as joints, heart valves, organ walls, arterial walls. The classic features are: articular hypermobility (elastic man), cutaneous hyper- elasticity, susceptibility to bleeding, bruising, hematomas and ecchymosis. Elastic man Cutaneous hyper-elasticity Articular hypermobility

12 The common oral manifestations in EDS:Retained primary teeth and the absence of some permanent teeth were commonly reported. Enamel hypoplasia. Deep & dome-shaped palate and bumpy lips. Gorlin Sign: Only 10% of the population can touch the tip of their nose with their tongue; common in individuals with EDS. Panoramic view revealed multiple impaction and calcification of stylohyoid ligament Deep & dome-shaped palate Bumpy lips Gorlin Sign

13 Important precautions for EDS-patients:Oral examinations can be of great help in the diagnosis of EDS and if the classic manifestations of the syndrome are present, the patient should be immediately referred to a specialist keeping the following precautions: Mitral valve is usually involved in these individuals and there is a need for prophylactic antibiotics. Short appointments are advised to avoid iatrogenic traumas to TMJ. Maxillofacial surgeries should be avoided as much as possible. In case such surgeries are absolutely necessary, the blood factors should be carefully checked preoperatively. Sutures may not be able to keep the mucosa in place and acrylic covers should be used. The dental surgeon should pay special attention to the oral mucosa as it is susceptible to injuries in such patients. The dental surgeon should be aware that inferior alveolar block injection may lead to hematoma. Orthodontic forces should be lighter than those in healthy individuals because such forces damage periodontal ligaments. The teeth are moved more easily and with milder forces, and root resorption is not considered a problem in such patients. A longer retention period should be considered because relapse is common.

14 Osteogenesis Imperfecta (OI)Osteogenesis imperfecta (brittle bone disease) or (Lobstein syndrome) It is a congenital bone disorder caused by poor quality collagen, or insufficient amounts of normal collagen (primarily type I), necessary for healthy, strong bones and certain other connective tissues. Most of OI cases are caused by mutations in the COL1A1 and COL1A2 genes, both of which code for type I collagen. It is characterized by brittle bones that are prone to fracture, shorter height, neurological features e.g.; seizures, blue sclera, hearing loss. The fractures themselves can cause acute or chronic pain, reduced quality of life, and depression. People with OI are born with defective connective tissue, or without the ability to make it. Diagnosis of OI is based on the clinical features & may be confirmed by collagen or DNA testing. Treatment: There is no cure for OI. Treatment is aimed at increasing overall bone strength to prevent fracture and maintain mobility using: bisphosphonates, surgery, physical therapy, and physical aids. Blue sclera

15 Oral cavity problems related to OI:A skeletal Class III malocclusion. An open bite. Impacted teeth. The first or second permanent molars do not erupt, or they erupt out of the usual location (ectopic). Tooth development may be delayed. Dentinogenensis imperfecta (DI) can occur with the first baby tooth that looks gray, bluish, or brown. Radiographs, or X-rays, can be useful but may be difficult to obtain. Crowns appear bulbous and roots may be shorter & more slender than standard. Primary teeth are usually more affected than the permanent teeth. Notice that: OI does not affect the presence or absence of periodontitis. DI can be part of OI or it can be a separate inherited dominant trait. Teeth affected by DI have normal enamel, but the DEJ and the dentin is not normal. The enamel tends to crack away from the dentin, which will wear away more quickly than enamel. The dentin makes the teeth look darker or opalescent. The dentin also grows to fill in the pulp chamber, causing a loss of feeling in the tooth. Affected teeth will have an increased incidence of fracture, wear and decay.

16 Important precautions for OI & DI-patients:Early orthodontic interventions are necessary when needed. Good care involves mechanical tooth brushing and flossing the teeth of young children (Proper teaching is very essential). Soft toothbrushes are good and easier on gums, since gums also need brushing. Use of fluoride toothpaste is recommended. Before going to bed, children should spit out the toothpaste after brushing, but not rinse their mouths. This will leave more fluoride in the mouth to work overnight. Children need to be monitored for cracking, chipping and abrasion of the teeth. Restorative treatment may be needed at some point.

17 II) Autoimmune CTDs The autoimmune CTDs may have both genetic & environmental causes. Genetic factors may create a predisposition towards developing these autoimmune diseases. They are characterized as a group by the presence of spontaneous over activity of the immune system that results in the production of extra antibodies into the circulation. The classic collagen vascular diseases have a "classic" presentation with typical findings that can easily recognized during examination. Each disease also has "classic" blood test abnormalities and abnormal antibody patterns. However, each of these diseases can evolve slowly or rapidly before demonstrating the classic features that help in the diagnosis.

18 Sjögren's syndrome (SS)Sjögren's syndrome (SS) is a long term autoimmune disease in which the moisture-producing glands of the body are affected. The hallmark is dryness (dry mouth and dry eyes). Other symptoms can include dry skin, a chronic cough, vaginal dryness, numbness in the arms and legs, feeling tired, muscle and joint pains, and thyroid problems. Lymphoma is possible in 5% of cases. It is more common in females. Types: Primary: when occurs by itself. Secondary: when occurs when another connective tissue disease e.g.; Rheumatoid arthritis. Treatment is symptomatic and supportive. Dental care: Preventive dental treatment is necessary, as xerostomia creates an ideal environment for the proliferation of bacteria. Treatments include topical fluoride application to strengthen tooth enamel and frequent teeth cleanings by a dental hygienist. Existing cavities must also be treated. This treatment regimen is the same as that used for all xerostomia patients, such as those undergoing head and neck radiation therapy.

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20 Rheumatoid Arthritis (RA)RA is an autoimmune disease resulting in persistent inflammatory synovitis, usually involving the peripheral joints with a symmetric distribution. RA is associated with many clinical signs and symptoms of which pain is a major problem; gross deformity of joints, systemic weight loss, fever, and fatigue may be the first presentation of RA. Limited movements, gelling (joint stiffness), and muscle spasm are also present in the later stages. Sjogren’s syndrome is a common oral finding. Tempromandibular joint: Most studies indicate that more than 50% of RA patients clinically exhibit TMJ involvement. The clinical findings in the TMJ affected with RA are similar to those described for other joints, that is, pain, swelling, movement impairment and crepitation. Pre-auricular pain or sensitivity during joint movement. The joints are tender upon pressure, and there is morning stiffness usually lasting more than 30 min and decreased masticatory force. Malocclusion of the teeth and anterior open bite may occur in advanced stages. Etiology: A combination of infection, autoimmunity and strong genetic factors are associated with the incidence of RA. T cells are key factors in the initiation of RA.

21 Pathogenesis

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23 Extra oral photograph showing restricted mouth openingRA affecting the TMJ presents as a diagnostic challenge to the dentist in the initial stages of disease course. Comprehensive clinical examination along with history are required. Hematologically certain abnormal blood antibodies are frequently found in patients with RA like “RF” and “ANA” and raised ESR values. Radiological examination is useful and important tool for diagnosis and assessment of TMJ disease. Mild bony changes not demonstrated by conventional radiographs are clearly seen by advanced imaging modalities (cone beam computed tomography [CBCT]). CBCT coronal view of closed mouth – a) right condyle revealing slight decrease in joint space Left condyle revealing loss of joint space and severe condylar erosions Extra oral photograph showing restricted mouth opening

24 Is there a relation between RA & periodontitis???Bingham and Moni, 2013

25 Treatment of RA: The main goal is to maintain function, and to prevent joint and organ damage until the disease enters remission. Two classes of medications are used in treating RA: Fast-acting “first-line drugs” such as aspirin and cortisone, are used to reduce pain and inflammation. The slow-acting second-line drugs (disease-modifying anti-rheumatic drugs), such as methotrexate, and hydroxychloroquine promote disease remission and prevent progressive joint destruction, but they are not anti-inflammatory agents. Some newer “second-line” drugs include leflunomide & the “biologic” medications etanercept, infliximab, rituximab, and abatacept. Physiotherapy can be used in the short-term to manage restricted mouth opening or after arthroscopy or open surgery. NSAIDs are indicated for pain secondary to inflammation. Joint pain can be temporarily relieved by injection of local anesthetic into the joint space, and pain relief suggests that arthroscopy may be considered as a therapeutic and diagnostic aid.

26 Scleroderma Signs & symptoms (Dental considerations???):It is a is a chronic systemic autoimmune disease characterized by hardening (sclero) of the skin (derma); In the more severe form, it also affects internal organs. It is more common in females. Etiology: genetic & environmental factors (Mutations in HLA genes). It is characterized by increased synthesis of collagen leading to the sclerosis (stiffening), damage to small blood vessels, activation of T lymphocytes and production of altered connective tissues. Signs & symptoms (Dental considerations???): Cardiovascular: Raynaud's phenomenon, skin & mucousal telangiectasis, palpitations, irregular heart rate and fainting due to conduction abnormalities, hypertension & congestive heart failure. Digestive: gastroesophageal reflux disease, loss of appetite, diarrhoea alternating with constipation, sicca syndrome and its complications, loosening of teeth, heartburn & hoarseness (due to acid reflux). Pulmonary: progressive worsening of shortness of breath, chest pain & dry, persistent cough. Musculoskeletal: joint, muscle aches, loss of joint range of motion, and muscle weakness. Genitourinary: scleroderma renal crises and kidney failure. Other: facial pain due to trigeminal neuralgia, hand paresthesias, headache, stroke, fatigue, calcinosis and weight loss. It may be systemic or localized.

27 Raynaud’s phenomenon:Painful attacks follow exposure of the digits to cold White then in turn cyanosed & erythematous before returning to normal color.. Prevention: keep digits and ears warm and dry Prophylaxis: vasodilator.

28 Diagnosis

29 Mixed connective tissue diseaseMixed connective-tissue disease (MCTD) is a disorder in which features of various connective-tissue diseases (CTDs) such as systemic lupus erythematosus (SLE); systemic sclerosis (SSc); dermatomyositis (DM); polymyositis (PM); anti-synthetase syndrome; and, occasionally, Sjögren syndrome can coexist and overlap. The course of the disease is chronic and usually milder than other CTDs. In most cases, MCTD is considered an intermediate stage of a disease that eventually becomes either SLE or Scleroderma.

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31 I) Acquired CTDs

32 Scurvy Symptoms of scurvy generally develop after at least 3 months of severe or total vitamin C deficiency, they includes: Weakness & fatigue Bruising easily & bleeding from weakening blood vessel, connective tissue & bones due to collagen loss. Hair, teeth loss & gingivitis . Infants may be irritable, have pain when they move, and lose their appetite. Infants do not gain weight. In infants and children, bone growth is impaired, and bleeding and anemia may occur.

33 The diagnosis of scurvy is mainly clinical, based on a dietary history of inadequate vitamin C intake and the signs and symptoms described here. Gums may swell and become red, soft and spongy. Any slight friction may cause the gums to bleed. This results in poor oral hygiene and dental diseases. Tooth loss can occur in the severe conditions.

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