Rheumatology Doctutorial

Add tocilizumab 162 mg SC QWK; taper prednisone

Start with Prednisone 0.75-1.0 mg/kg/d (not >40-60 mg/d).

If there is no response, move to the Moderate to severe weakness branch of treatment.

Start with Prednisone 1 mg/kg/d (not >60-80 mg/d).

Options include IVIg, mycophenolate mofetil, cyclosporine, tacrolimus.

The gender ratio for APLA is 9:1, with females being more affected than males.

APLA is associated with both arterial and venous thrombosis, as well as pregnancy morbidity.

Antibodies against phospholipids, such as Beta 2 glycoprotein and prothrombin, predispose individuals to develop thrombosis.

Antibodies against cardiolipin (ACL) are detected using an enzyme-linked immunosorbent assay (ELISA) with cardiolipin as the antigen.

The two main types of APLA are:

1. Primary APLA

   • Occurs without any particular underlying cause.
   • Also known as Hughes syndrome.

2. Secondary APLA

   • Associated with other diseases, most commonly Systemic Lupus Erythematosus (SLE) and lymphomas.

Catastrophic APLA is characterized by thrombosis involving three or more organs, organ systems, or tissues occurring over a period of one week.

Lupus anticoagulant is a type of antiphospholipid antibody that can be detected using tests such as activated partial thromboplastin time (aPTT) and kaolin clotting time. It is found in approximately one-third of patients with Systemic Lupus Erythematosus (SLE) who have antiphospholipid antibodies.

The common manifestations of venous thrombosis in APLA include:

The common manifestations of arterial thrombosis in APLA include:

Livedo reticularis is the skin condition characterized by a lacy-like network pattern, often seen in patients with Antiphospholipid Antibody Syndrome (APLA).

The most common cause of mortality for long-standing SLE is coronary artery disease.

Infection is the most common cause of mortality in early-stage SLE.

Lupus nephritis is a fulminant presentation of SLE that can lead to mortality.

Neurologic manifestations include:

• Renal artery thrombosis
• Renal vein thrombosis
• Glomerular thrombosis
• Fibrous intima hyperplasia

1. Vascular thrombosis: One or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ.

2. Pregnancy morbidity: Includes complications such as preeclampsia and fetal loss.

The clinical criteria for diagnosing APLA include:

1. One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation,
2. One or more premature births of a morphologically normal neonate before the 34th week of gestation due to eclampsia, severe pre-eclampsia, or recognized features of placental insufficiency,
3. Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded.

The laboratory criteria for diagnosing APLA include:

1. Lupus anti-coagulant present in plasma on two or more occasions at least 12 weeks apart, detected according to the guidelines of the international society and thrombosis and hemostasis.
2. Anti-cardiolipin antibody of immunoglobulin (Ig)G or IgM isotype in serum or plasma, present in medium or high titer (>40 GPL or MPL, or >99th percentile), on two or more occasions at least 12 weeks apart, measured by a standardized ELISA.

The presence of Anti-B2-glycoprotein I antibody of IgG or IgM isotype in serum or plasma (in titer > 99th percentile) on two or more occasions at least 12 weeks apart indicates a diagnosis of Antiphospholipid Antibody Syndrome (APLA).

If a patient is totally asymptomatic and has an incidentally found increased aPTT, no treatment is required.

For individuals developing a thrombotic episode (arterial or venous), anticoagulation is recommended. In the acute stages, treatment includes LMWH/Heparin plus warfarin for the initial 3-5 days. Once warfarin reaches the therapeutic range, it should be continued lifelong with a target INR of 2-3.

The treatment for recurrent thrombosis involves using LMWH/Heparin combined with Warfarin. Once Warfarin reaches the therapeutic range, it should be continued lifelong with a target INR of 3-4. Additionally, consider adding low dose aspirin (81 mg or 75 mg).

For pregnant females with Antiphospholipid Antibody Syndrome, LMWH should be used throughout the pregnancy. After delivery, Warfarin is recommended as a lifelong anticoagulant, and low dose aspirin may also be considered.

The two forms of scleroderma are:

1. Localized Scleroderma

   • Morphea
   • Linear scleroderma

2. Generalized Scleroderma

   • Limited cutaneous systemic sclerosis
   • Diffuse cutaneous systemic sclerosis

The two phases of the etiopathogenesis of systemic sclerosis are:

1. Inflammatory phase
2. Fibrotic phase

Systemic sclerosis has a prevalence ratio of 5:1, with females being more affected than males.

Vascular insult, which can be caused by factors such as viruses, cytotoxic factors, autoantibodies, and environmental influences, leads to endothelial cell (EC) injury and is a critical step in the development of vasculopathy in systemic sclerosis.

Endothelial dysfunction in systemic sclerosis results in:

• Reduced nitric oxide (NO) and prostacyclin (PGI)
• Increased endothelin-1 (ET-1) and thrombin
• Vasoconstriction and impaired relaxation
• Ischemia-reperfusion injury and reactive oxygen species (ROS) generation

Endothelial cell injury can lead to several pathways, including:

1. EC apoptosis
2. Endothelium dysfunction
3. Defective ECP mobilization
4. Luminal narrowing

The final outcome of tissue hypoxia in systemic sclerosis is the release of fibrosing growth factors, which ultimately leads to fibrosis.

In systemic sclerosis, the tunica media of pulmonary arterioles exhibits hypertrophy, while the tunica intima shows thickening.

The two forms of cutaneous involvement in systemic sclerosis are:

1. Limited cutaneous form - Shading primarily on the hands, forearms, feet, and lower legs.
2. Diffuse cutaneous form - Shading across the entire body.

• Limited cutaneous SSC: 90%
• Diffuse cutaneous SSC: 100%

• Limited cutaneous SSC: 35%
• Diffuse cutaneous SSC: 65%

• Limited cutaneous SSC: 50%
• Diffuse cutaneous SSC: 25%

• Limited cutaneous SSC: 2%
• Diffuse cutaneous SSC: 15%

• Limited cutaneous SSC: 99%
• Diffuse cutaneous SSC: 98%

Nail fold capillaroscopy can show various patterns in systemic sclerosis:

Dark bluish-black fingertips indicate digital gangrene, which is a severe complication associated with systemic sclerosis.

Raynaud's phenomenon is characterized by the narrowing of blood vessels in response to cold or stress, leading to color changes in the fingers. The stages include:

1. Discoloration: Initial stage shows tips of fingers turning pale or blue.
2. Wounds: Progression may lead to open wounds and discoloration around knuckles.
3. Severe discoloration: In advanced stages, fingers may appear purplish or blackened due to severe blood flow restriction.

Acro-osteolysis refers to the dissolution or shortening of the terminal parts of the distal phalanges, as seen in X-ray images. This condition is indicative of severe vascular damage and is often associated with systemic sclerosis, reflecting the extent of tissue ischemia and necrosis.

Sclerodactyly is characterized by shiny skin and tightening of the fingers, indicating fibrosis and skin thickening. This condition is a hallmark of systemic sclerosis and reflects underlying connective tissue involvement and vascular changes.

Telangiectasias are small, widened blood vessels that give the skin a red, blotchy appearance. They are commonly found around the nose and cheek areas.

Periungual telangiectasias are small, widened blood vessels that appear near the nail bed, manifesting as red lines or spots.

Calcinosis cutis presents as small, white or yellowish nodules on the skin, indicating calcium deposits. It is most commonly found in a limited form of systemic sclerosis.

The components of CREST syndrome include:

1. C - Calcinosis cutis
2. R - Raynaud's phenomenon
3. E - Oesophageal dysmotility
4. S - Sclerodactyly
5. T - Telangiectasia

The characteristic facial appearance associated with systemic sclerosis in CREST syndrome is known as mask-like facies, which can also be described as a mouse-like or fish mouth appearance.

Gastrointestinal manifestations may involve the entire digestive tract from oral to anal, including:

1. Oesophageal dysmotility - Impaired movement of the esophagus.
2. Pseudo obstruction of the intestine - Symptoms resembling intestinal blockage without a physical obstruction.

GAVE stands for Gastric Antral Vascular Ectasia, and it is commonly referred to as watermelon stomach due to its appearance.

The principal manifestations of GAVE in the stomach include:

1. Gastroparesis
2. Gastric antral vascular ectasia (GAVE, watermelon stomach)

The gastrointestinal manifestations associated with systemic sclerosis include:

The most common interstitial lung disease (ILD) associated with lung involvement is NSIP (Nonspecific Interstitial Pneumonia).

Pulmonary arterial hypertension is a condition associated with lung involvement in this context.

The typical findings in pulmonary function tests for lung involvement with extensive fibrosis show a restrictive pattern.

The CT imaging characteristics of lung involvement in interstitial lung disease include:

1. Normal lungs
2. Ground glass opacities
3. Extensive fibrosis

Interstitial lung disease (ILD) is the most common cause of mortality in systemic sclerosis.

Thrombotic microangiopathy is characterized by the presence of schistocytes in the peripheral blood smear, indicating microvascular damage and hemolysis, which can occur in systemic sclerosis.

In the early stages of renal involvement in systemic sclerosis, ACE inhibitors can be used, and their use has been associated with improved prognosis.

• Tendon friction rubs
• Digital ischemia ulcers
• Extensive skin involvement
• Early crisis

• Digital ischemic ulcers
• Calcinosis cutis
• Isolated pulmonary arterial hypertension (PAH)
• Rare renal crisis

• Rapidly progressive skin involvement
• Tendon friction rubs
• Joint contractures
• Gastrointestinal bleeding (GAVE)
• Renal crisis
• Contemporaneous cancers
• Rare digital ulcers

• Pulmonary arterial hypertension (PAH)
• Interstitial lung disease (ILD)
• Scleroderma renal crisis
• Gastrointestinal tract involvement
• Myositis

• Interstitial lung disease (ILD)
• Pulmonary arterial hypertension (PAH)

• Calcinosis cutis
• Interstitial lung disease (ILD)
• Myositis overlap

• Systemic lupus erythematosus (SLE)
• Myositis overlap

• Pulmonary arterial hypertension (PAH)
• Inflammatory arthritis
• Myositis overlap

• Interstitial lung disease (ILD)

Vasodilators (CCB or PDE5 inhibitors) and anti-platelet therapy.

ARBs, CCB, prostacyclin, or renal transplant (after waiting at least 12 months).

Upper GI: Dental/periodontal care, lifestyle modifications, proton pump inhibitors, prokinetics. Lower GI: Probiotics, rotational antibiotics.

Mycophenolate mofetil or cyclophosphamide.

Research trials involving novel biologics and antifibrotic drugs.

PDE5 inhibitors, ETA, combination therapy (PDE5i+ETA), prostacyclin, PRA, or soluble guanylate-cyclase stimulators.

Immunosuppression or IVIG for myocardial inflammation.

Prednisone, methotrexate, TNF inhibitors, or rituximab tocilizumab.

IVIG.

Sjogren's syndrome is characterized by a chronic progressive course and lymphocytic infiltration of exocrine glands, leading to autoimmune exocrinopathy.

The two types of Sjogren's syndrome are:

1. Primary Sjogren's syndrome
2. Secondary Sjogren's syndrome - which is associated with other diseases such as Rheumatoid arthritis, SLE, Systemic Sclerosis, MCTD, primary biliary cirrhosis, autoimmune thyroid disease, and chronic active hepatitis.

The glandular manifestations of Sjogren's syndrome include:

• Dry mouth (Xerostomia)
• Burning sensation of oral mucosa
• Dry and erythematous oral mucosa
• Difficulty in swallowing

Sjogren's syndrome predominantly affects middle-aged females, with a female to male ratio of 9:1.

The common ocular symptoms include:

• Dry eyes (Keratoconjunctivitis sicca)
• Foreign body sensation
• Itching
• Redness
• Photophobia

The extra glandular manifestations include:

• Lung involvement:

  • Small airways
  • Interstitial lung disease (ILD-NSIP)
  • Lymphocytic interstitial pneumonitis

• Kidney involvement:

  • Tubulo-interstitial involvement
  • Glomerular involvement (can occur with immune complex mediated diseases like cryoglobulinemia)
  • Renal tubular acidosis type I (Distal RTA)

The indicators of Sjogren's syndrome include:

1. Persistent parotid enlargement
2. Purpura
3. Cryoglobulinemia
4. Leucopenia
5. Low C4 levels
6. Anti-Ro (SS-A)
7. Anti-La (SS-B)

Being anti-Ro and anti-La positive is associated with a more severe disease course in Sjögren's syndrome.

The tests used to diagnose dry eyes include:

1. Schirmer’s test - Measures tear production.
2. Rose Bengal testing - Detects corneal erosion.

To classify as primary Sjögren's syndrome, a patient must have:

• At least one symptom of ocular or oral dryness
• A total score of 4 or greater from the following criteria:
  • Histopathology showing focal lymphocytic sialadenitis (3 points)
  • Presence of anti-Ro/SS-A antibodies (3 points)
  • SICCA ocular staining score ≥5 (1 point)
  • Schirmer's test <5 mm (1 point)
  • Unstimulated salivary flow <0.1 mL/min (1 point)

• History of head and neck radiation treatment
• Active hepatitis C infection (confirmed by PCR)
• AIDS
• Sarcoidosis
• Amyloidosis
• Ability to undergo minor salivary gland biopsy

• Supportive therapy
• Dry eyes: Artificial tears, Methyl cellulose drops
• Dry mouth: Water, saliva substitutes
• Joint involvement: Hydroxychloroquine (HCQ) or Methotrexate + Steroids
• Interstitial lung disease (ILD): Cyclophosphamide pulse therapy

Sarcoidosis is characterized by non-caseating granulomas.

The potential sources of antigens in sarcoidosis include:

1. Infectious antigens
2. Organic particles
3. Inorganic agents

Sarcoidosis is most commonly found in females.

Propionibacterium acnes is one of the infection agents associated with granulomas in Sarcoidosis.

The mycobacterial protein mkatG is detected on the surface of granulomas in Sarcoidosis.

Lofgren's syndrome includes the following clinical features:

1. Erythema nodosum
2. Bilateral lymphadenopathy
3. Arthritis

Heerford's syndrome includes the following clinical features:

1. Bilateral LMN facial palsy
2. Parotitis
3. Uveitis

The most common organ involved in chronic sarcoidosis is the lungs.

Common symptoms of lung involvement in chronic sarcoidosis include cough and dyspnea.

The staging system used for lung involvement in chronic sarcoidosis is based on chest X-ray (CXR) findings, specifically Scadding's staging system.

The second most common organ involved in chronic sarcoidosis is the skin.

The next most commonly involved organ after the lungs and skin in chronic sarcoidosis is the eyes.

1. Stage I: Bilateral hilar lymphadenopathy
2. Stage II: Bilateral hilar lymphadenopathy + Pulmonary infiltrates
3. Stage III: Pulmonary infiltrates only
4. Stage IV: Pulmonary fibrosis

In sarcoidosis, the interstitial lung disease (ILD) typically presents as a Non-Specific Interstitial Pneumonia (NSIP) pattern.

Garland's sign indicates bilateral hilar lymphadenopathy with right paratracheal node involvement, which is significant in the diagnosis of sarcoidosis.

Lupus pernio is characterized by chronic inflammatory skin lesions, predominantly appearing as reddish papules over the face, associated with sarcoidosis.

The most common eye involvement in sarcoidosis is anterior uveitis. Other types include posterior uveitis and retinitis.

Neurological manifestations in neuro sarcoidosis can include:

1. Bilateral lower motor neuron (LMN) facial palsy
   • Differential diagnoses include:
     • Sarcoidosis
     • Guillain-Barré Syndrome (GBS)
     • Lyme disease
     • Diphtheria
2. Optic neuritis

Neurological complications include:

1. Hypothalamic involvement
2. Pituitary stalk involvement
3. Basal meningitis
4. Transverse myelitis

Cardiac conditions include:

• Rare occurrences of cardiomyopathy
• Types of cardiomyopathy: Restrictive > Dilated
• Arrhythmias

Renal involvement in sarcoidosis is characterized by tubulointerstitial involvement.

Sarcoidosis can lead to hypercalcemia through:

• Granulomas producing 1,25 dihydroxycholecalciferol
• This production results in increased calcium levels, leading to renal involvement.

Hematological findings include:

• Lymphopenia
• Anemia of chronic disease

The most common laboratory finding is an increase in alkaline phosphatase (ALP) levels.

The lifetime risk of lung involvement is 95% with a follow-up rate of 94%.

24% of patients experience skin involvement, with a follow-up percentage of 43%.

Liver involvement has a presentation percentage of 12%, which is lower than lung (95%), skin (24%), and higher than spleen (7%) and neurologic (5%) involvements.

The follow-up percentage for liver involvement is 14%.

• Bilateral hilar lymphadenopathy
• Rash
• Arthritis
• Lofgren's syndrome

• CXR (Chest X-Ray)
• CT thorax
• Serum ACE levels (increased, but not specific)
• PET scan
• Biopsy (to identify granulomas, can be endobronchial or transbronchial)

Schaumann bodies are inclusions made of calcium and protein that appear as dense, laminated, basophilic structures within giant cells. They are indicative of sarcoidosis.

In a bronchoalveolar lavage (BAL) study for sarcoidosis, the following findings are typically observed:

1. Increased lymphocytosis
2. Increased CD4:CD8 ratio

The Panda Sign and Lambda Sign are radiological signs associated with sarcoidosis:

• Panda Sign: Indicates involvement of the lacrimal glands and parotid glands.
• Lambda Sign: Represents an upside-down 'Y' shape indicating lymph node enlargement in the right and left paratracheal regions.

The Panda sign indicates the involvement of the lacrimal and parotid glands in sarcoidosis.

The Lambda sign indicates the involvement of the right and left paratracheal lymph nodes (LN) and pretracheal LN in sarcoidosis.

In the management algorithm for sarcoidosis, if a patient has minimal to no symptoms with abnormalities, the first step is to consider systemic therapy if there are neurologic, cardiac, ocular, or calcium abnormalities; otherwise, no therapy and observe.

For single organ disease in sarcoidosis affecting the anterior eye, localized skin, or cough, the recommended treatment is to try topical steroids; if not effective, then consider systemic therapy.

For symptomatic multiple organ involvement in sarcoidosis, the recommended treatment is systemic therapy with glucocorticoids (e.g., prednisone). If tapering to less than 10 mg in less than 6 months is not possible or if there is glucocorticoid toxicity, consider methotrexate, hydroxychloroquine, or azathioprine.

1. If glucocorticoids are not tolerated:
   • Consider alternative agents.
   • If the dose is <10 mg/d, continue therapy with alternative agents such as:
     • Methotrexate
     • Hydroxychloroquine (if effective, taper off glucocorticoids)
     • Azathioprine
     • Leflunomide
     • Mycophenolate
     • Minocycline
     • Infliximab
     • Cyclophosphamide
     • Thalidomide
2. If the alternative agents are not effective, consider multiple agents.

IgG4-related disease is an immune-mediated, multisystem disorder with an unknown inciting agent, potentially triggered by various factors leading to T cell and B cell interactions and cytokine production.

Clinical features of IgG4-related disease can involve multiple organs, including:

1. Lacrimal glands
2. Salivary glands
3. Thyroid (Riedel's thyroiditis, presenting as a firm to hard thyroid)
4. CNS (involvement of meninges and pituitary stalk)
5. Lungs (interstitial lung disease and tumor-like lesions)
6. Liver

Cytokines produced during the immune response in IgG4-related disease contribute to a fibrotic process, leading to the formation of tumor-like lesions. Key cytokines include IL-1β, TGF-β, and IFN-γ, which are involved in the pathogenesis of the disease.

In IgG4-related disease, plasma cell activation leads to a dominant IgG4 response, which is a hallmark of the disease's immunopathogenesis, resulting from the interactions between T cells and B cells.

• Dacryoadenitis: Enlargement of the lacrimal gland
• Sialoadenitis: Enlargement of the salivary glands
• Interstitial pneumonia: Lung inflammation
• Sclerosing cholangitis: Inflammation and scarring of bile ducts
• Hepatic pseudotumor: Liver mass-like lesions
• Chronic thyroiditis: Inflammation of the thyroid gland
• Prostatitis: Inflammation of the prostate gland
• Retroperitoneal fibrosis: Fibrous tissue growth in the retroperitoneal space

The key histopathological features include:

1. Lymphoplasmacytic infiltrate
2. Storiform fibrosis
3. Obliterative phlebitis

The first-line treatment for autoimmune pancreatitis is steroids. In cases where patients do not respond to steroids, Rituximab (anti-CD 20) may be used.

In autoimmune pancreatitis, there is typically an increase in Serum IgGu levels.

• Most common chronic inflammatory disease
• Symmetrical polyarthritis
• Involves both skeletal and extra skeletal manifestations

• Multifactorial causes:
  • Genetic factors:
    • HLA DR4 (main)
    • HLA DR1
  • Environmental factors:
    • Smoking
    • Porphyromonas gingivalis
    • Prevotella
• More common in females than males
• Typically affects individuals aged 25-55 years

T cells, upon activation by antigen presenting cells, differentiate into TH1 and TH17 cells. These cells release various cytokines that stimulate T effector cells and B cells, leading to the production of antibodies such as Rheumatoid factor and Anti-CCP.

TH1 cells release cytokines such as IFN, TNF, and Lymphotoxin, while TH17 cells release IL-17A, IL-17F, TNF, IL-6, and GM-CSF. These cytokines play a crucial role in the inflammatory process and activation of B cells.

The activation of T cells leads to the production of antibodies including Rheumatoid factor (IgM against Fc of IgG) and Anti-CCP (cyclic citrullinated peptide).

TH1 and TH17 cells contribute to the pathogenesis by releasing cytokines that activate B cells and promote the production of pro-inflammatory mediators, leading to joint inflammation and damage.

The primary site of pathology in Rheumatoid Arthritis is the synovium. The consequences of synovitis include the formation of pannus, which is an inflammatory mass responsible for the destruction of bones, cartilages, and ligaments.

TNF-a activates osteoclasts, which are pivotal in causing bone erosion in Rheumatoid Arthritis.

Early non-specific symptoms of Pre-RA include various skeletal and extra-skeletal manifestations that may not be clearly defined but indicate the onset of rheumatoid arthritis.

Skeletal manifestations of Pre-RA include:

1. Bilateral symmetric polyarthritis
2. Predominantly involves small joints of the hands and feet
3. Early joints involved:
   • MCP (Metacarpophalangeal joints)
   • Wrist joint

The differences between pre-clinical RA and clinical RA are summarized in the following table:

The Z deformity, also known as hitchhiker thumb, is characterized by hyperextension of the interphalangeal (IP) joint of the thumb and subluxation of the first metacarpophalangeal (MCP) joint.

The zig-zag deformity is characterized by:

• Radial deviation of metacarpals
• Ulnar deviation of fingers

The characteristic deformities associated with rheumatoid arthritis include:

1. Swan neck deformity: Finger bent upwards at the proximal interphalangeal joint (PIP) and downwards at the distal interphalangeal joint (DIP).
2. Boutonniere deformity: Involves flexion at the PIP joint and hyperextension at the DIP joint.
3. Z deformity of the thumb: A specific angulation of the thumb due to joint changes.
4. Radial deviation of the metacarpals: The metacarpals deviate towards the radial side.
5. Dorsal subluxation of the distal ulna: The distal ulna is displaced towards the dorsal side.
6. Ulnar deviation of the fingers: The fingers deviate towards the ulnar side.
7. Zig-zag deformity: A pattern of joint deformity seen in the fingers.

Pianokey deformity is due to the rupture of the extensor carpi ulnaris tendon.

The metatarsophalangeal joint is the most commonly affected joint in the lower limb.

The type of arthritis associated with psoriasis is known as erosive arthritis.

In rheumatoid arthritis, X-rays typically show inflamed and swollen joints, particularly in the finger joints.

• Atlantoaxial subluxation (C1-C2)
• Cervical myopathy
• Carpal tunnel syndrome

• Keratoconjunctivitis sicca (most common)
• Episcleritis
• Scleritis
• Scleromalacia perforans

The common skin manifestations include:

1. Rheumatoid nodules - most common, seen in 30-40% of RA patients.
2. Purpura.
3. Pyoderma gangrenosum.

Rheumatoid nodules are characterized by:

• Painless nodules.
• Predominantly located on the extensor aspect over the elbow and achilles tendon.
• Most common in individuals with RA factor positivity.
• Can undergo ulceration and necrosis.
• May also be present in the lungs.

The most common lung involvement in rheumatoid arthritis is pleuritis, which can occur with or without effusion.

Exudative effusion with lymphocyte predominance is characterized by low sugar values.

The most common type of interstitial lung disease (ILD) is Usual Interstitial Pneumonia (UIP).

UIP is characterized by honeycomb appearances on CT scans, while NSIP shows ground glass opacities.

The syndrome associated with rheumatoid arthritis and pneumoconiosis is known as Caplan's syndrome.

The most common hematological manifestation in patients with APLA is normocytic normochromic anemia.

Felty's syndrome includes nodular rheumatoid arthritis, neutropenia, and splenomegaly.

Large granular lymphocytic leukemia is associated with large granular lymphocytes.

The most common cardiac manifestations associated with DLBCL include:

• Pericarditis (most commonly involved)
• Increased risk of atherosclerosis
• Increased risk of coronary artery disease (CAD), which is the most common cause of death
• Mitral regurgitation, the most common valvular lesion

The renal manifestations commonly seen in DLBCL include:

• Membranous nephropathy (most common)
• Secondary amyloidosis

The gastrointestinal manifestation that can occur due to vasculitis in DLBCL is mesenteric ischemia.

Early morning stiffeners that last for one hour are indicative of rheumatoid arthritis.

C-reactive protein (CRP) is indicative of active joint inflammation in rheumatoid arthritis.

A score of ≥ 6 points is required for a definite diagnosis of rheumatoid arthritis according to the 2010 ACR-EULAR criteria.

The scoring for joint involvement is as follows:

In the classification criteria for rheumatoid arthritis, serology results are scored as follows:

The categories of DMARDs include:

Folic acid is used to reduce toxicity associated with certain medications, particularly methotrexate, which is commonly prescribed for rheumatoid arthritis.

If there is no contraindication for methotrexate, the initial treatment option is to start with methotrexate. If there is a clinical diagnosis of rheumatoid arthritis, it is recommended to combine methotrexate with short-term glucocorticoids.

If poor prognostic factors are present, such as high levels of RF/ACPA, high disease activity, or early joint damage, the treatment plan should include adding a biological DMARD (bDMARD) or a JAK-inhibitor.

For patients with contraindications for methotrexate, the recommended initial treatments are leflunomide or sulfasalazine.

Monitoring improvement at 3 months and achieving target at 6 months is crucial for determining whether to continue with the current treatment plan, including potential dose reduction or interval increase in sustained remission, or to escalate treatment if necessary.

• Axial predominant: Involves spine, pelvis, ribcage
• Asymmetric oligoarthritis
• HLA-B27 positivity
• Strong familial aggregation
• Enthesitis: Inflammation of enthesis (tendons, ligaments, joint capsule)
• Sacroiliitis
• Anterior uveitis
• Negative RA factor and anti-CCP
• No extra-articular features of RA

1. Sacroiliitis on imaging plus ≥1 SpA feature
2. HLA-B27 plus ≥2 other SpA features

Ankylosing spondylitis is the prototype disorder. It predominantly affects males (M > F) and typically presents in the 2nd to 3rd decade of life.

The genetic factor associated with Ankylosing spondylitis is HLA B27, which is present in 75-90% of cases.

The genetic factors include HLA-B27, IL-23R, and PGER4.

The environmental factors include smoking, infections, and mechanical stress.

The most important cytokine is TNF-alpha.

The clinical features include:

1. Low backache (lower lumbar & gluteal region)
2. Inflammatory backache
3. Sacroiliitis

Inflammatory LBP typically has an age of onset of less than 40 years, while mechanical LBP can occur at any age.

Inflammatory LBP has an insidious onset, whereas mechanical LBP usually has an acute onset, often following an injury.

Inflammatory LBP symptoms last more than 3 months, while mechanical LBP symptoms last less than 4 weeks.

Morning stiffness in inflammatory LBP lasts more than 60 minutes, while in mechanical LBP it lasts less than 30 minutes.

Exercise improves inflammatory low back pain but exacerbates mechanical low back pain.

Alternating buttock pain is present in early disease of inflammatory low back pain, but it is not present in mechanical low back pain.

Common findings include tenderness over the sacroiliac joint and decreased chest expansion (normal is greater than 5 cm).

1. Identify the posterior superior iliac spine and join both lines.

2. Draw a line 5 cm below and 10 cm above this line.

3. Ask the patient to flex forward; note that some may find it difficult to flex.

4. Measure the distance:

   • Normal person: distance increase → 22 cm
   • In Ankylosing Spondylitis (AS): distance increase → 17 cm, indicating limitation of spinal flexion.

The most common extra skeletal manifestations of ankylosing spondylitis include:

• Acute anterior uveitis (30-40%)
• Apical fibrosis
• Aortic regurgitation
• Amyloidosis
• Colitis

The severity of ankylosing spondylitis is assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scoring system.

The first choice treatments for ankylosing spondylitis include:

• NSAIDs
• TNF-α inhibitors such as: i. Infliximab ii. Etanercept
• IL-17A inhibitor: Secukinumab

'Bamboo spine' refers to a radiological finding associated with ankylosing spondylitis, characterized by fusion of the vertebrae leading to a rigid spine resembling bamboo. This condition is part of the seronegative spondyloarthritides group.

'Dagger spine' indicates calcification of the supraspinous and interspinous ligaments, which is a radiological feature seen in certain types of spondyloarthritides, particularly in ankylosing spondylitis.

Common infections that can lead to reactive arthritis include:

• Enteric infections: Shigella, Salmonella
• Urogenital infections: Chlamydia
• Upper Respiratory Infections (URI)

The typical age range for reactive arthritis is 18-40 years, with a prevalence of Males (M) > Females (F).

The characteristics of arthritis in reactive arthritis include:

• Sterile/non-purulent arthritis
• Asymmetrical additive mono/digoarthritis
• 30-50% chronicity

Monoarthritis is characterized by inflammation of a single joint, often presenting with symptoms such as swelling, redness, and pain in the affected area. It can be indicative of various underlying conditions.

Enthesitis refers to inflammation at the site where tendons or ligaments insert into the bone. It is commonly observed at points such as the Achilles tendon insertion, leading to swelling and pain in that area.

Dactylitis, also known as 'sausage digits', refers to the swelling of an entire digit (finger or toe), giving it a sausage-like appearance. This condition is often associated with inflammatory arthritis.

The extra-skeletal manifestations include:

1. Anterior uveitis
2. Mucocutaneous manifestations:
   • Keratoderma blennorrhagia
   • Circinate balanitis
   • Serpinginous ulcers on the glans penis (Circinate balanitis)

The first choice treatment for ankylosing spondylitis is NSAIDs, specifically Indomethacin.

The diagnosis of urethritis and conjunctivitis can be supported by clinical diagnosis and an increase in ESR and CRP levels.

• Intra-articular steroids are administered for monoarthritic conditions.
• Topical steroids are used for conditions like keratoderma blennorrhagia and circinate balanitis.
• TNF α inhibitors are also a treatment option.

• Septic arthritis
• Crystal Associated Arthropathies (CAA)

Synovial fluid analysis is crucial for diagnosis, where septic arthritis typically shows a lot of neutrophils and polarized microscopy may demonstrate crystals.

• 60-70% of psoriatic arthritis cases occur in patients with psoriasis.
• 20% have both psoriasis and arthritis.
• 20% develop arthritis before psoriasis.

HLA associations:

• HLA B27 is positive in many cases.
• HLA CW6 is associated with psoriasis.
• HLA B57 and HLA DR7 are associated with psoriatic arthritis.
• HLA DQ3 is also noted.

The most common pattern is asymmetrical oligoarthritis.

• D/P arthritis
• Dactylitis

The common nail changes associated with psoriatic arthritis include:

1. Nail pitting
2. Onycholysis (separation of the nail from the nail bed)
3. Ridging of nails
4. Yellowish color changes
5. Hyperkeratosis (thickening of the skin under the nail)

Nail changes in arthritis mutilans may include:

• Nail pitting: Small depressions on the surface of the nails.
• Nail ridging: Vertical or horizontal ridges on the nails.
• Onycholysis: Separation of the nail from the nail bed.
• Deformities: Severe changes in nail shape and structure due to underlying bone deformities.

• Uveitis
• Apical pulmonary fibrosis

To meet the CASPAR criteria, a patient must have inflammatory articular disease (joint, spine, or entheseal) with ≥3 points from any of the following five categories:

1. Evidence of current psoriasis, a personal history of psoriasis, or a family history of psoriasis
2. Typical psoriatic nail dystrophy observed on current physical examination
3. A negative test result for rheumatoid factor
4. Either current dactylitis or a history of dactylitis recorded by a rheumatologist
5. Radiographic evidence of juxtaarticular new bone formation in the hand or foot

• Anti TNF α inhibitors → Drug of choice (DOC)
• Methotrexate
• IL 17 monoclonal antibodies:
  • Secukinumab
  • Ixekizumab

The treatment options for Enteropathic arthritis include:

1. TNF α inhibitors
2. Secukinumab (IL 12/23 monoclonal)
3. JAK inhibitor - Tofacitinib
4. PDE-4 inhibitor - Apremilast

The main types of crystal arthropathies include:

1. Gout
2. Pseudogout
3. Calcium hydroxyapatite deposition disease
4. Calcium oxalate deposition disease

The nonmodifiable risk factors for gout include:

1. Age
2. Gender
3. Ethnicity
4. Genetic variants

The modifiable risk factors for gout include:

1. Obesity
2. Hypertension
3. Hyperlipidemia
4. Cardiovascular disease
5. Diabetes mellitus
6. Chronic kidney disease
7. Dietary factors
8. Alcohol
9. Medications altering urate balance

Gout most commonly affects middle-aged males, typically between the ages of 40 to 60 years.

The primary crystal involved in gout is monosodium urate (MSU), which results from the deposition of uric acid, the end product of purine metabolism.

• Thiazide diuretics
• Loop diuretics

• Salicylates (Low dose)
• Nicotinic acid
• Pyrazinamide

• Cyclosporine
• Ethambutol
• Ethanol
• Colony stimulating factors

MSU crystals activate the NLRP3 inflammasome, leading to the production of pro-inflammatory cytokines such as interleukin 1 beta, which contributes to inflammation and acute flares.

1. Hyperuricemia
2. MSU crystal deposition
3. NLRP3 inflammasome activation
4. Acute flare
5. Aggregated NET formation
6. Flare resolution
7. Tophaceous gout

• Asymptomatic hyperuricemia
• Acute gouty arthritis
• Painful arthritis
• First joint involved: MTP point
• Symptoms: Pain, swelling, redness, tenderness
• Intercritical gout: Period between two episodes
• Risk factors: Asymptomatic hyperuricemia may predispose to coronary and cerebrovascular accidents due to its relation to insulin resistance and metabolic syndrome profile.

Inflamed tophaceous gout is characterized by the presence of tophi, which are large, swollen, and red areas typically found on joints and surrounding tissues due to the accumulation of urate crystals. Commonly affected areas include fingers and the knee joint.

Martel's sign is an X-ray finding that indicates the presence of subchondral bone erosions associated with gout. It is characterized by specific areas highlighted on the X-ray, suggesting joint damage due to chronic inflammation from urate crystal deposition.

Crystal-associated arthropathies are a group of conditions characterized by joint inflammation due to the deposition of crystals in the joints. The most common types include gout (urate crystals) and pseudogout (calcium pyrophosphate crystals).

• Urate nephropathy: Predominantly affects the tubulo-interstitium.
• Increased risk of nephrolithiasis: Higher likelihood of kidney stone formation due to uric acid.

• Normal synovial cell count: <200 cells/ML.
• In gout: Elevated cell count of 3000-6000 cells/µL.
• Demonstration of MSU crystals: Identified using polarizing microscopy.

Uric acid crystals are negatively birefringent, needle-shaped, and appear brightly colored against a dark background, with colors ranging from yellow to blue.

The two main strategies for treating gout are:

1. Inhibiting urate production

   • Medications: Allopurinol, Febuxostat

2. Normalizing renal urate excretion

   • Medications: Probenecid, Lesinurad, Benzbromarone

Additionally, Pegloticase can be used to metabolize urate.

Key findings associated with gout include:

• X-ray: Erosive arthritis
• USG: Double contour sign
• LFT: Liver function tests
• RFT: Renal function tests
• Fasting lipid profile
• S. urine acid: Normal levels

1. NSAIDs: Ibuprofen & Naproxen
2. Colchicine: 0.6mg TID (with side effects including diarrhea)
3. Steroids: Oral steroids or intra-articular steroids
4. Allopurinol: Not recommended during acute attacks as it decreases uric acid production, potentially leading to flare-ups.

The target uric acid level for individuals with chronic gout is less than 6 mg%. Hyperuricemia is defined as uric acid levels greater than 6.8 mg%.

Individuals with HLAB 5801 have an increased risk of developing:

• Stevens-Johnson syndrome
• Bone marrow suppression
• Hepatotoxicity
• Chronic Kidney Disease (CKD): Requires renal dose modification.

Febuxostat:

• No dose reduction is required in cases of Chronic Kidney Disease (CKD).
• Should be withdrawn in case of Cerebrovascular Accident (CVA).

Uricosuric drugs, such as Probenecid, are used in the treatment of chronic gout to help lower uric acid levels.

Pseudogout is also known as Calcium pyrophosphate deposition disease (CPPD).

Pseudogout may be asymptomatic, or present as acute, subacute, or chronic conditions. It is most common in elderly males and can mimic gouty arthritis.

Conditions associated with calcium pyrophosphate crystal deposition disease include:

1. Aging
2. Primary hyperparathyroidism
3. Hemochromatosis
4. Hypophosphatasia
5. Hypomagnesemia
6. Chronic gout
7. Post meniscectomy
8. Gitelman's syndrome
9. Epiphyseal dysplasia

The commonest joint affected is the knee.

Chondrocalcinosis is the calcification of cartilage, which can be identified on an X-ray as areas of calcification, often indicated by arrows pointing to the affected regions.

The treatment options for calcium hydroxyapatite deposition disease include:

1. NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)
2. Steroids

Weak positive birefringent rhomboid crystals appear as rhomboid-shaped crystals that show weak positive birefringence when viewed under polarized light, typically against a bright pink and blue background.

Destructive arthropathy on X-ray images is characterized by significant joint damage, which can be seen in comparative images showing the joint before and after the condition has progressed, often indicated by arrows pointing to the affected areas.

The most common shoulder joints include the glenohumeral joint, acromioclavicular joint, and sternoclavicular joint.

Joint fluid aspiration is important for diagnosing joint conditions as it allows for the examination of joint fluid under electron microscopy to demonstrate the presence of crystals, which can indicate conditions like gout or pseudogout.

Calcium oxalate deposition diseases are primarily associated with chronic kidney disease (CKD), leading to various complications including kidney stones and potential renal failure.

Bipyramidal shaped crystals, when observed under microscopic examination, typically indicate the presence of calcium oxalate, which can be associated with conditions like kidney stones or metabolic disorders.

Vasculitis is characterized by inflammation of the vessel wall.

The three categories of blood vessels affected by vasculitis are:

1. Large Vessels
2. Medium Vessels
3. Small Vessels

The 2012 Revised International Chapel Hill Consensus Conference focuses on the nomenclature and classification of vasculitides.

The main types of ANCA-associated small vessel vasculitis include:

1. Microscopic Polyangiitis
2. Granulomatosis with Polyangiitis (GPA) - also known as Wegener's granulomatosis
3. Eosinophilic Granulomatosis with Polyangiitis (EGPA) - also known as Churg-Strauss vasculitis

Examples of immune complex mediated vasculitis include:

• Cryoglobinemic Vasculitis
• Goodpasture Syndrome
• Henoch-Schonlein Vasculitis
• Hypocomplementemic Vasculitis

Variable vessel vasculitis is characterized by its ability to affect blood vessels of different sizes. Examples include:

• Behcet's Disease
• Cogan's Syndrome
• Single-organ vasculitis such as 1º angiitis of the CNS and 1° CNS vasculitis.

1. Granulomatosis with polyangiitis (Wegener's)
2. Microscopic polyangiitis
3. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
4. Cryoglobulinemic vasculitis
5. IgA vasculitis (Henoch-Schönlein)
6. Polyarteritis nodosa
7. Kawasaki disease
8. Giant cell arteritis
9. Takayasu arteritis
10. Behçet's disease
11. Cogan's syndrome
12. Single-organ vasculitis
13. Cutaneous leukocytoclastic angiitis
14. Cutaneous arteritis
15. Primary central nervous system vasculitis
16. Isolated aortitis

1. Hepatitis C virus-associated vasculitis
2. Hepatitis B virus-associated vasculitis
3. Cancer-associated vasculitis
4. Vasculitis associated with systemic disease
5. Lupus vasculitis
6. Rheumatoid vasculitis
7. Sarcoid vasculitis

Giant cell arteritis primarily affects the elderly population, specifically individuals over the age of 50, with a higher prevalence in females compared to males.

The most common clinical feature of temporal arteritis is headache.

Common clinical features include:

1. Headache
2. Jaw claudication
3. Fatigue and myalgia
4. Fever (PUO)
5. Polymyalgia rheumatica (40-50%) - stiffness in neck, shoulder, lower back, hips, and thighs
6. Visual loss due to Anterior Ischemic Optic Neuropathy (AION)

HLA DR₄ is associated with the etiopathogenesis of temporal arteritis, indicating a genetic predisposition to the disease.

The disease is initiated in the tunica adventitia of the arteries.

76% of patients experience headache as a symptom in GCA.

Common symptoms include:

1. Headache - 76%
2. Weight loss - 43%
3. Fever - 42%
4. Fatigue - 39%
5. Any visual symptom - 37%
6. Anorexia - 35%
7. Jaw claudication - 34%
8. Arthalgia - 30%
9. Unilateral visual loss - 24%
10. Bilateral visual loss - 15%
11. Vertigo - 11%
12. Diplopia - 9%

The superficial temporal artery is typically dilated and tortuous, and it is tender on palpation.

The halo sign indicates the presence of inflammation in the temporal artery, which is a key finding in diagnosing giant cell arteritis. It reflects the thickening of the arterial wall due to vasculitis.

The criteria include:

1. Age at disease onset ≥ 50 years: Symptoms begin at age 50 or older.
2. New headache: New onset or change in type of headache.
3. Temporal artery abnormality: Tenderness or decreased pulsation of the temporal artery.
4. Elevated ESR: ESR ≥ 50 mm/hr by the Westergren method.
5. Abnormal artery biopsy: Biopsy shows vasculitis with mononuclear cell infiltration or granulomatous inflammation with multinucleated giant cells.

A patient is classified as having giant cell arteritis if at least three of these criteria are met.

The presence of any three or more criteria yields a sensitivity of 93.5% and a specificity of 91.2% for diagnosing giant cell arteritis.

Skip lesions in giant cell arteritis refer to areas of inflammation that are not continuous, which can complicate diagnosis and treatment. These lesions can lead to missed diagnoses if biopsies are taken from non-inflamed areas, as the disease may not be uniformly distributed along the affected arteries.

The halo sign observed in duplex ultrasound indicates the presence of a hypoechoic area surrounding the artery, which is suggestive of inflammation in the vessel wall, characteristic of giant cell arteritis.

Management of giant cell arteritis typically includes:

1. Corticosteroids: High-dose corticosteroids are the first-line treatment to reduce inflammation and prevent complications such as vision loss.
2. Monitoring: Regular follow-up to assess response to treatment and adjust dosages as necessary.
3. Immunosuppressive agents: In cases of steroid resistance or relapsing disease, additional immunosuppressive medications may be considered.
4. Management of complications: Addressing any complications that arise, such as vision problems or vascular issues.

Solumedrol 1000 mg IV for 3 days

Continue prednisone alone

Begin prednisone 60 mg/d

Re-evaluate diagnosis

• Arm claudication
• Raynaud's phenomenon

The subclavian artery has 93% of arteriographic abnormalities, with potential clinical manifestations including:

• Arm claudication
• Raynaud's phenomenon

• Visual changes
• Syncope
• Transient ischemic attacks
• Stroke

• Hypertension
• Renal failure

The abdominal aorta has 47% of arteriographic abnormalities, with potential clinical manifestations including:

• Abdominal pain
• Nausea
• Vomiting

• Onset before age 40 years
• Limb claudication

• Decreased branchial artery pulse
• Unequal arm blood pressure (>10mm Hg)
• Subclavian or aortic bruit
• Angiographic evidence of narrowing or occlusion of aorta or its primary branches or large limb arteritis

• Steroids
• Tocilizumab
• Angioplasty

The age range commonly affected by polyarteritis nodosa is 50 to 60 years.

The clinical manifestations associated with renal involvement include renal failure and hypertension.

The organ system with the highest percent incidence of clinical manifestations in polyarteritis nodosa is the musculoskeletal system, with a 64% incidence.

Common clinical manifestations of the gastrointestinal tract include abdominal pain, nausea and vomiting, bleeding, bowel infarction and perforation, cholecystitis, hepatic infarction, and pancreatic infarction.

The percent incidence of cardiac involvement in polyarteritis nodosa is 36%, with associated clinical manifestations including congestive heart failure, myocardial infarction, and pericarditis.

The clinical manifestations associated with peripheral nervous system involvement include peripheral neuropathy and mononeuritis multiplex.

There is no ANCA association in polyarteritis nodosa.

A key characteristic of polyarteritis nodosa is that there is no granuloma formation.

• Associated with Hepatitis B infection (30%)
• Associated with hairy cell leukemia

1. Weight loss ≥4kg
2. Livedo reticularis
3. Testicular pain or tenderness
4. Myalgias, weakness, or leg tenderness
5. Mononeuropathy or polyneuropathy
6. Diastolic blood pressure >90mm Hg
7. Elevated blood urea nitrogen or creatine levels
8. Hepatitis B virus
9. Arteriographic abnormality
10. Biopsy of a small or medium-sized artery containing polymorphonuclear neutrophils

• Steroids
• Cyclophosphamide

1. P-ANCA (Perinuclear Anti-Neutrophil Cytoplasmic Antibodies)

   • Against myeloperoxidase
   • Found in azurophilic granules of monocytes and neutrophils

2. C-ANCA (Cytoplasmic Anti-Neutrophil Cytoplasmic Antibodies)

   • Against proteinase-3
   • Present in granules of neutrophils

1. Granulomatosis with polyangiitis (GPA)
2. Microscopic polyangiitis
3. Eosinophilic granulomatosis with polyangiitis (EGPA)
4. Renal limited vasculitis

Wegener's granulomatosis

Individuals aged 40-50 years

Upper respiratory tract, lower respiratory tract, kidneys, eyes, skin, and CNS

It involves both vasculitis and granuloma formation, specifically necrotizing granuloma.

• Sinusitis
• Serous otitis media
• Nasal septal involvement (saddle nose deformity)
• Subglottic stenosis
• High recurrence of granulomatosis with chronic nasal carriage of Staphylococcus

• Pulmonary nodules
• Cavities
• Infiltrates
• Alveolar hemorrhage
• Cough
• Dyspnea
• Hemoptysis

• Glomerulonephritis
• Vasculitis

The common clinical manifestations at disease onset include:

1. Ear/Nose/Throat: 73%
2. Sinusitis: 51%
3. Lung: 45%
4. Glomerulonephritis: 18%
5. Nasal disease: 36%
6. Otitis media: 25%
7. Hearing loss: 14%
8. Subglottic stenosis: 1%
9. Ear pain: 9%
10. Oral lesion: 3%

The percentages of clinical manifestations throughout the course of the disease are as follows:

The highest diagnostic yield is with lung biopsy.

Microscopic polyangiitis typically affects individuals aged 45-55 years and has a higher prevalence in males (M > F).

The key clinical features include:

1. Renal: Rapidly Progressive Glomerulonephritis (RPGN)
2. Cutaneous: Purpura
3. Lung: Diffuse alveolar hemorrhage

Microscopic polyangiitis is characterized by necrotizing vasculitis without granuloma.

Churg-Strauss syndrome is characterized by:

1. Asthma
2. Tissue and blood eosinophilia
3. Extravascular granulomas
4. Vasculitis of multiple organ systems

Common clinical features include:

• Asthma with pulmonary infiltrates
• Eosinophil count > 1000/μL
• Vasculitis skin rashes, purpura

The most common cause of mortality in Eosinophilic Granulomatous Polyangiitis is myocardial involvement.

1. Steroids
2. Steroids + Cyclophosphamide
3. Mepolizumab - monoclonal antibody against IL-5, which is the most potent eosinophil activating cytokine.
   • Can be used for Churg-Strauss vasculitis.

Pneumocystis jirovecii prophylaxis should be considered for all patients.

For patients on CYC, consider sperm banking or ovarian protection.

For EGPA without poor prognostic factors, administer low-dose steroids with or without a steroid-sparing agent if needed.

For EGPA with poor prognostic factors, use CYC with steroids or MTX/AZA with or without low-dose steroids.

For non-organ-threatening GPA or MPA, use MTX with steroids or MTX with or without low-dose steroids.

For refractory disease, consider RTX, AZA, or CYC with steroids.

For small-vessel vasculitis with systemic or organ-threatening disease, use CYC or RTX with steroids.

In remission, consider RTX, MTX, or AZA with or without low-dose steroids.

Churg-Strauss syndrome is characterized by asthma and eosinophilia, and it is associated with granuloma presence.

Immune complex mediated vasculitis includes IgA vasculitis (Henoch-Schonlein purpura), Goodpasture syndrome, cryoglobulinemic vasculitis, and cutaneous leukocytoclastic vasculitis.

• Palpable, non-thrombocytopenic purpura on the buttocks and extensor aspects
• Gastrointestinal symptoms (70% of cases):
  • Nausea
  • Vomiting
  • Colicky abdominal pain (bowel angina)
  • Blood and mucus in stools
  • Constipation
  • Diarrhea
• Renal involvement leading to glomerulonephritis
• Arthralgia/arthritis

The criteria include:

1. Palpable purpura
2. Age at onset <20 years
3. Bowel angina
4. Vessel wall granulocytes on biopsy

Additionally, a skin biopsy may show leucocytoclastic vasculitis and treatment typically involves steroids at a dosage of 1mg/kg/day.

The primary clinical feature of cryoglobulinemic vasculitis is palpable purpura.

• Multisystem disorder
• Oral and genital ulcers
• Ocular involvement: uveitis, episcleritis, scleritis
• CNS involvement: neurobehcet's disease, brainstem involvement
• Superficial thrombophlebitis
• Deep venous thrombosis

• Antiviral
• Rituximab
• Steroids

• Behcet's disease
• Cogan's syndrome

The common mucocutaneous manifestations include:

Ocular manifestations of Behcet's disease include:

• Anterior/posterior uveitis
• Pan uveitis
• Iridocyclitis
• Keratitis
• Episcleritis
• Vitritis
• Optic neuritis
• Retinal vein occlusion

These ocular issues occur in approximately 40-60% of patients.

Vascular complications associated with Behcet's disease include:

Neurologic manifestations can include:

• CNS involvement
• Peripheral nervous system involvement

These occur in approximately 3% - 25% of patients.

Gastrointestinal symptoms in Behcet's disease may include:

• Chronic diarrhea
• Mucosal ulceration

These symptoms are seen in about 3%-26% of patients.

Musculoskeletal symptoms include:

• Arthritis
• Arthralgia

These symptoms are reported in approximately 45%-60% of patients.

1. A blunt hypodermic needle is inserted into the skin at an angle of 30° tangentially (4 pricks).

2. A reading is taken after 24-48 hours.

3. Look for papule or pustule formation as a response.

Diagnosis is established by a score of ≥4, with points assigned as follows:

• Perivasculitis
• Early neutrophil infiltration
• Endothelial swelling

• Anti-saccharomyces cervisea antibodies
• Antibodies to selenium binding protein
• Antibodies to enolase targeting endothelial cells

• Topical steroids

• Colchicine for mucocutaneous manifestations combined with arthritis.

• Systemic steroids for uveitis and neuro Behcet's symptoms.

• Cyclophosphamide is used for treating pulmonary aneurysms.

• Interstitial keratitis
• Audio vestibular symptoms such as vertigo.

• Muscle weakness
• Raised creatinine kinase
• Inflammatory muscle biopsy

• Dermatomyositis
• Polymyositis
• Immune Mediated Necrotising Myopathy (IMNM)
• Anti-synthetase syndrome
• Overlap syndrome
• Inclusion body myositis

• Most common inflammatory myopathy
• Can affect all ages
• Acute to subacute symptoms
• Symmetric proximal muscle weakness
• Neck weakness
• Extra-ocular muscles spared

The characteristic rash is known as heliotrope rash, which appears as a violaceous red rash over the periorbital region.

The 'V sign' indicates a rash in the anterior aspect of the neck, which is a distinct feature of inflammatory myopathies.

The Shawl sign refers to a rash that appears over the neck and upper back, often associated with certain skin conditions, particularly dermatomyositis. It indicates a specific pattern of skin involvement that can help in diagnosing underlying inflammatory myopathies.

Gottron's papules are erythematous or violaceous papules that occur over the metacarpophalangeal (MCP) and interphalangeal (IP) joints. They are characteristic of dermatomyositis and can help in the diagnosis of inflammatory myopathies.

Periungual telangiectasias are small dilated blood vessels around the nail cuticle area, often seen in conditions like scleroderma and dermatomyositis. Their presence can aid in the diagnosis of these connective tissue diseases.

Calcinosis cutis is a condition characterized by calcium deposits forming in the skin, and it is more likely to occur in juvenile dermatomyositis.

Anti-Mi-2 antibodies are associated with classical skin rash, moderate muscle involvement, and a favourable response to immunotherapy.

Anti-TIF-ty antibodies are strongly associated with cancer, present with a severe skin rash that appears as hypo-pigmented red on white patches, and show variable degrees of muscle involvement.

Anti-NXP-2 antibodies are associated with an increased risk of malignancy, classic skin rash, mild-to-moderate muscle involvement, and subcutaneous features.

The clinical features include:

• Anti-MDA-5: Severe skin rash, no/minimal muscle involvement, skin ulcerations, and rapidly progressive interstitial lung disease.
• Anti-SAE: Classic rash, mild muscle involvement, and dysphagia.

• Similar to dermatomyositis
• Symmetric proximal muscle weakness
• Neck weakness
• Pharyngeal weakness

• Muscle involvement is common.
• Progressive interstitial lung disease is a significant concern.
• May present with a mild skin rash and mechanic's hands.

The most common antibody is anti-JO-1, which is associated with muscle involvement and interstitial lung disease.

Overlap syndrome is a myopathy associated with concurrent Systemic Lupus Erythematosus (SLE) and Sjogren's syndrome. It is characterized by the presence of anti-Ro 52 antibodies.

Key EMG findings in inflammatory myopathies include:

1. Fibrillation potentials
2. Positive sharp waves
3. Increased insertional activity
4. Low amplitude short duration
5. Polyphasic MUAP (Multiple Unit Action Potential)

They are associated with inclusion body myositis, which is most common in individuals over 50 years of age.

Commonly involved muscle groups include:

• Quadriceps
• Finger flexors
• Wrist flexors
• Ankle dorsiflexors

The biopsy shows inflammation leading to atrophy.

The skin condition is characterized by ragged fibres and the presence of rimmed vacuoles. Additionally, there are noticeable patches of red inflammation around the knee area.

The treatment shows a poor response to immunosuppressants, and supportive therapy is recommended.