Spondylitis and It's Pharmacotherapy

Brief about Spondylitis

1. SPONDYLITIS Dr.Pooja Sharda Janardan

2. Spondylitis Spondylitis  is a form of arthritis that primarily affects the spine, although other joints can become involved. It causes inflammation of the spinal joints (vertebrae) that can lead to severe, chronic pain and discomfort. In more advanced cases this inflammation can lead to ankylosis -- new bone formation in the spine, causing sections of the spine to fuse in a fixed, immobile position. Spondylitis affects men more often than women.

3. Types of Spondylitis- Pott's Disease/Spine Ankylosing Spondylitis Spondylodiscitis

4. ETIOPATHOGENESIS Condition Reasons Bone spurs These  overgrowths of bone  are the result of the body trying to grow extra bone to make the  spine  stronger. The extra bone can press on delicate areas of the spine, such as the spinal cord and  nerves , resulting in pain. Dehydrated spinal discs Loss of fluid between the spinal  discs cause the friction of bones, leads to degenerative disease Herniated discs Single excessive strain or injury may cause a herniated disc. A herniated disc refers to a problem with one of the rubbery cushions (discs) that sit between the individual bones (vertebrae) that stack to make your spine. Injury An injury to neck can also leads to same condition. Ligament stiffness The tough cords that connect your spinal bones to each other can become even stiffer over time, which affects your neck movement and makes the neck feel  tight Overuse Continuously sitting or repetitive weightlifting can leads to spondylitis.

5. Risk factors Diagnosis Neck injuries Work-related activities Genetic factors Smoking Obesity Physical examination- Reflexes Sensory deficits Neck motion Radiology- X-ray CT scan MRI

6. Pott's Disease/Spine Pott disease, also known as tuberculous spondylitis, is a classic presentation of extra pulmonary tuberculosis (TB). Pott’s disease results from haematogenous spread of tuberculosis from other sites, often the lungs.   Pott’s Disease is a combination of osteomyelitis and arthritis which involves multiple vertebrae The typical site of involvement is the anterior aspect of the vertebral body adjacent to the subchondral plate and occurs most frequently in the lower thoracic vertebrae. 8-10% worlwide

7. It can cause- Vertebral collapse, Kyphotic deformity of the spine, Compression fractures, Spinal deformities, Neurological insults, Paraplegia

8. Clinical presentation Back pain Fever Localized Tenderness Muscle Spasms Restricted Spinal Motion Occasional chills Wheezing sound during breathing Dizziness and fatigue Weight loss  Impaired sensation Paresis

9. Clinical Menifestations Spinal Involvement Neurological deficits Cervical Spinal TB Co-morbidities Immunosuppressive Disorders HIV/AIDS TB Gastrectomy Peptic Ulcer Drug Addiction Alcoholism Malnourishment

10. Diagnosis- The Mantoux Test Erythrocyte Sedimentation Rate (ESR)  Microbiology Studies  CT scan MRI Biopsy PCR Etiology Paradiscal Anterior Granuloma Central Lesions

11. Systemic Menifestations Involvment Menifestations Musculoskeletal Vertebral Fractures, Vertebral Collapse, Spinal Ligament Destruction, Intervertebral Disc Destruction, Paravertebral Abscess, Muscle Atrophy, Kyphotic Deformity, Osteoporosis Neurological Paresthesia , Paralysis, Paresis, Abnormal Muscle Tone, Abnormal Reflexes, Cauda Equina Syndrome, Myelomalacia , Cardiovascular Spinal Artery Infarction, Avascularity of Intervertebral Discs, Thrombosis Integumentary Ulcers, Abscess, Cutaneous Fungal Infections Urogenital Bladder Dysfunction,Bowel dysfunction

12. Pharmacological Treatment Anti-TB drugs shall be given to treat tubercular complications like Pott’s spine.

13. Ankylosing Spondylitis AS  is a form of arthritis that primarily affects the spine, although other joints can become involved. It causes inflammation of the spinal joints (vertebrae) that can lead to severe, chronic pain and discomfort .

14. Clinical Presentation S tiffness and pain in your lower back in the early morning. Pain in one or both buttocks. N eck , shoulder, or thigh pain. Chest pain or a tightness. Fatigue,

15. Diagnosis SLR, 90° X-ray MRI (Sacroiliac Joint) Possible complications Osteoporosis Lumbar fracture Cervical spondylosis Disc displacement Toe/finger swelling Uveitis

16. NSAIDs Nonsteroidal anti-inflammatory drugs (NSAIDs) A nkylosing spondylitis is associated with the prostaglandin E receptor 4 (PTGER4) gene. This receptor is associated with bone absorption; NSAIDs inhibit prostaglandin production, thus reducing the absorption.

17. Naproxen 500 mg PO,OD for 7-21 days Maximum dose- 1500mg per day, for 1-2 weeks Aceclofenac 100mg, OD/BD/TDS PO Diclofenac 50-100mg OD/BD/TDS PO Side effects- I ndigestion , heartburn, stomach pain, nausea, dizziness , bruising , itching, rash, tinnitus Monitor RFT if taking for longer duration.

18. O pioid analgesic Tramadol is widely used, at dose 50-100mg It can also given in combination with diclofenac 25mg, PO

19. Side effects- Somnolence, gastric irritation, headache, blurred vision, mania, dependence, Indication- To be use only when pain score is more than 7. Monitoring- HR, BP, Pain score

20. BIOLOGIC MEDICATIONS

21. TNF Inhibitors These medications have been shown to be highly effective in treating not only the arthritis of the joints, but also the inflammation in the gut and eyes, as well as the spinal arthritis associated with ankylosing spondylitis and related diseases . Improves pain, function and other symptoms of AS I mproves spinal inflammation

22. Adalimumab 40mg/IV Etanercept 50mg SC weekly Infliximab 5 mg/kg IV 0-6 weeks Side effects- Headache . Abdominal pain Nausea, vomiting, or heartburn. Weakness. Cough. Redness, itching, pain, or swelling at the site of injection.

23. Monitoring- WBC, RBC, hemoglobin, platelets, AST, ALT and ESR/CRP

24. IL-17 Inhibitor Secukinumab 150mg IV per day Ixekizumab 80mg IV per day Side effects- Injection site reactions, weight gain Nausea, Rhinitis, Insomnia, Hypersensitivity Monitoring parameters- Neutrophil count, Temperature Acts by inhibiting IL-17, involved in inflammation Test dose should be given before starting treatment with biological agents.

25. Corticosteroids Corticosteroids have a anti-inflammatory effect and can be taken as PO or IV for treatment of AS. Acts by binding to cellular glucocorticoid receptors,  corticosteroid  acts by inhibiting inflammatory cells and suppresses expression of inflammatory mediators Prednisolone 10mg- 80mg, divided doses. PO Hydrocortisone 100-500mg/IV/IM/PO, (slow dose-10mg-100mg)

26. Prednisone 8mg-32mg, PO, (less used) Contraindications- Vaccines, Psychotropic agents, NSAIDs Side effects- Itching, Insomnia, Increase appetite, Increase weight Type D ADR

27. Antimetabollite Methotrexate is an antimetabollite as well as immunosuppressant. In rheumatoid arthritis, methotrexate reduces inflammation and damage to joints. Acts by inhibiting T-cell immune response, responsible for cell mediated immune reactions. Initial dose- 7.5mg PO once a week Maximum dose 25mg PO once a week

28. Side effects- Anemia, stomach pain or upset, diarrhea, hair loss, tiredness, dizziness, chills, headache, mouth sores Special indication - Add Folic acid PO 5mg while giving methotrexate . Monitoring parameters- Hb , ESR, LFT, RFT, Vitamin B and Vitamin K Interactions- Theophylline , NSAIDs, Phenytoin , Probenecid , Amoxicillin, Ampicillin

29. Sulfasalazine Sulfasalazine  has immunomodulatory effect. Inhibits AICAR transformylase and, as such, promotes the accumulation of adenosine and its anti-inflammatory  actions  via the adenosine A 2A   receptor Dose- 500-1000   mg PO, OD/BD This drug is used when treatment with corticosteroid is not working.

30. Side effects- headache, increased sensitivity to sunlight, skin rash or itching, vomiting, black urine, abdominal pain, infections, bruising Monitoring parameters- Bleeding time, clotting time, RF factor, CRP Contra-indications- Digoxin, Amoxicillin, PCM, Naproxen, Etoricoxib , Adalimumab Hematologic toxicity, G6PD deficiency Hemophillia

31. Leflunomide Given to the patients failed with MTx Anti-inflammatory L eflunomide inhibits the reproduction of rapidly dividing cells -  lymphocytes, modifies immune reactions, inhibits the mitochondrial enzyme dihydroorotate dehydrogenase 100 mg PO OD for 3 days, then maintain dose at 10-20mg PO OD per day

32. Side effects- Diarrhea, RTI, UTI, dyspepsia, pruritis , dry skin. Interactions- Adalimumab , Anakinra , Zetanercept , losartan , phenytoin Contraindications- Pregnancy,Liver disease,  Hepatitis B/C, Active serious infections, Hypersensitivity Monitor LFTs, RF factor, ESR

33. Treatment Drug class Reasoning Examples 1 st Line agents NSAIDs OR Opioid analgesics 2-4 weeks Treats pain and reduce inflammation Naproxen, Aceclofenac Tramadol IF NO/LOW RELIEF 2 nd Line agents Biologics – TNF Inhibitors IL-1 7 inhibitors 4-8 weeks Treats spinal inflammation Adalimumab , Infliximab Secukinumab Ixekizumab IF NO/LOW RELIEF OR NOT SO SEVERE STATE OR DMARDs for 4-8 weeks Anti- rheumatics Prednisolone . Methotrexate Sulfasalazine With PHYSIOTHERAPY

34. Spondylodiscitis Defined as a primary infection (accompanied by destruction) of the intervertebral disc ( discitis ), with secondary infections of the vertebrae ( spondylitis ), starting at the endplates.  It can lead to osteomyelitis of the spinal column. It has a high morbidity and mortality and is a rare but serious infection

35. Spondylodiscitis is the most common complication of sepsis. Pathogens responsible spondylodiscitis are Staphylococci, Escheria coli and Mycobacterium tuberculosis.

36. Risk Factors Infection Diabetes mellitus Age Cardiovascular diseases Obesity  Chronic steroid intake Alcoholism and smoking HIV infection Serious traumas Chemotherapy, human immunodeficiency virus infections, or chronic alcoholism Rheumatic diseases   Renal failure

37. Clinical Presentation Back or neck pain, more worse at night Radicular pain radiating to the chest or abdomen Fever Spinal deformities, Neurological deficits: leg weakness, paralysis, sensory deficit, Cervical lesion  Local tenderness Limb weakness Epidural abcess formation Hip pain Loss of lower back movement Poor bladder control Spinal tenderness Paravertebral muscle spasm

38. Diagnosis MRI PET( Positron-emission tomography) X-ray Biopsy Blood Culture  Leukocyte count C-reactive protein ESR Disease Monitoring Visual Analogue Scale (VAS) Oswestry disability index (ODI)

39. TREATMENT Antibiotics and immobilization of the spine. Surgery- Posterior decompression and stabilization of a spondylodiscitis

40. Exercises Back streching Leg stretching Planks Cobra’s Sun salutation