Canakinumab

Biological drug.
MOA: Antibody to IL-1β.
Used: in JIA, adult onset Still's disease, Gout.

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Retinopathy is the serious complication, but this is rare before 6 years of treatment in Hydroxychloroquine and Chloroquine.

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Differences between primary and secondary Raynaud’s syndrome.

1-Age
P- 15-30 years, less than 30 years
S- More than 30 years

2-Gender
P- Female >male
S- F: M, 4:1

3-Family history
P- Present
S- Absent

4-Symmetry
P- Symmetrical
S- Asymmetrical

5-Gangrane&Ulceration
P-Absent
S-Present

6-ANA
P- negative
S- positive

7-Capillary nail-fold loops test
P- negative
S- positive "fallout".

P-Primary
S-Secondary

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Other features in SScl,"rare":

-Entrapment neuropathy
-Facial nerve palsy
-Autonomic dysfunction
-Hypothyroidism
-Impotence
-Primary liver cirrhosis
-Pneumonitis
-Pleural effusion
-Alveolar cell carcinoma.

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In Raynaud’s syndrome

Drugs to be avoided:

-Beta-blocker
Non-selective agents
•Alprenolol
•Bucindolol
•Carteolol
•Carvedilol
•Labetalol
•Nadolol
•Penbutolol
•Pindolol
•Propranolol
•Sotalol
•Timolol
-Ergotamine
-Oral contraceptive
-Sympathomimetic:
-Alpha and beta agonists
Salbutamol, phenylephrine, isoproterenol, and dobutamine.

Drugs may be given:

-Calcium antagonist (diltiazem and nifedipine)
-ACE inhibitor
-Angiotensin II receptor blocker
(valsartan)
-Aspirin
-Epoprostenol"prostacyclin analog"
-Sympatholytic" alpha blocker not beta "Prazosin (α1 inverse agonist).

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Rheumatic disorders that maybe associated with secondary Raynaud's phenomenon:

[systemic scleroderma (85%), SLE (35%), DM (30%), Sjögren syndrome, rheumatoid arthritis, polyarteritis nodosa].

Others:
Diseases with abnormal blood proteins (cryoproteins, cold agglutinins, macroglobulins)

Drugs (β-adrenergic blockers, nicotine)

Aterial diseases (arteriosclerosis obliterans, thromboangiitis obliterans).

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Causes of proximal myopathy:

-Myopathy (limb girdle, fascioscapulohumeral), except myotonic dystrophy which causes distal.
-Myasthenia gravis
-Muscular dystrophy
-Myasthenic myopathic syndrome (Eaton-Lambert syndrome).


1-Inflammatory:
• Polymyositis
• Dermatomyositis
• Inclusion body myositis (predominantly distal effects).

2-Endocrine:
Endocrine/metabolic
• Hypothyroidism
• Hyperthyroidism
• Acromegaly
• Cushing’s syndrome
(including iatrogenic, steroids)
• Addison’s disease
• Conn’s syndrome
• Diabetic amyotrophy
• Hyperparathyroidism.

3-Metabolic:
• Osteomalacia
• Hypokalaemia (liquorice, diuretic and purgative abuse)
• Hypercalcaemia (disseminated bony metastases)
• Paraneoplastic
• Carcinomatous neuromyopathy
• Periodic paralysis
•Carnitinedeficiency
•Phosphofructokinase deficiency
•Myophosphorylase deficiency.

4-Rheumatology:
• Dermatomyositis, Polymyositis, SLE, RA, SScl.

5-Toxic:
• Alcohol (chronic and acute syndromes)
• Amphetamines/cocaine/heroin
• Vitamin E
• Organophosphates
• Snake venoms.

6-Drugs:
• Glucocorticoids
• Statins
• Amiodarone
• β-blockers
• Opiates
• Chloroquine
• Ciclosporin
• Vincristine
• Clofibrate
• Zidovudine
• Fibrates
• Pencillamine
• Colchicine
• Tumour necrosis factor
inhibitors.

7-Infections:
• Viral (HIV, cytomegalovirus, rubella, Epstein–Barr, echo)
• Parasitic (schistosomiasis, cysticercosis, toxoplasmosis)
• Bacterial (Clostridium perfringens, staphylococci, tuberculosis, Mycoplasma).

مجمع من عدة كتب.
مهم جداً،قد يجي writing، أو بيتكرر كثير على هيئة all of the following except.

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CPK may be normal in dermatomyositis:

1- If dermatomyositis is associated with internal malignancy.
2- Due to long standing disease with atrophy of muscles.
3- Due to the presence of inhibitors in blood.

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Causes of high CPK:

1-Exercise
2-Intramuscular injection
3-Muscle trauma or road traffic accident, prolonged immobilization after a fall
4-Convulsion
5-Alcoholism
6-Dermatomyositis or polymyositis
7-Acute myocardial infarction (CPK-MB)
8-Myopathy
9-Rhabdomyolysis
10-Chronic liver disease (CLD)
11-Motor neuron disease
12-Hypothyroidism
13-Muscular dystrophy
14-Viral myositis
15-Drugs—statins, busulfan, narcotics, colchicine ,pencillamine and chloroquine.

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Atypical features of SLE?

1- Raynaud’s phenomenon
2- Chorea
3- Repeated abortion
4- Epilepsy or cerebrovascular accident (CVA) in young age
6- Psychiatric disorder.

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Mild SLE:

• Fever
• Arthralgia or arthritis
• Rash, headache
• Mild pericarditis or mild pericardial effusion
• Mild pleural effusion.

Severe SLE:

• Massive pleural effusion
• Massive pericardial effusion
• Renal involvement
• CNS involvement
• Acute vasculitis
• Myocarditis
• Lupus pneumonitis
• Hemolytic anemia
• Thrombocytopenic purpura.

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In Systemic Sclerosis"SScl":


-ANA is positive in about 70%.
-About 30% of patients with "diffuse" dcSScl have antibodies to topoisomerase 1 (Scl70).
-About 60% of patients with "limited" lcSScl syndrome have anticentromere antibodies.

Bosentan

MOA: endothelin-1 antagonist.
Uses: treating ischaemic digital ulcers in severe Raynaud’s syndrome in SScl.
Also early treatment of Progressive pulmonary hypertension.

"Watermelon stomach"

Recurrent occult upper gastrointestinal bleeding may indicate it (antral vascular ectasia; up to 20% of patients with systemic sclerosis).

Pneumatosis cystoides intestinalis, in which there is radiolucent cyst or streaks in the wall of small intestine due to air in the intestinal wall can occur.

The patient presents with severe abdominal pain.

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In SLE:

-The most common respiratory complication of SLE is PLEURISY.

-Most common muscloskeltal manifastation of SLE
is ARTHRALGIA 100٪.

-Most common renal complication of SLE is diffuse lupus.Also most severe.

-The most common haematologic features of SLE is lekupenia/lymphopenia.

-The most common cause of death in SLE is the renal impairment.

-Most common dermatologic manifastations or characteristic of SLE is MALAR RASH.

-The most common cardiac complication of SLE is PERICARDITIS.

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-Anti-ribonucleoprotein antibody (anti-RNP) is in Mixed connective tissue disease (100%) and SLE (25–50%), usually in conjunction
with anti-Sm antibodies.

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Causes of Seronegative arthritis:

1-Ankylosing spondylitis
2-Psoriatic arthritis
3-Behcet disease
4-Reiter's syndrome "Reactive arthritis"
5-Enteropathic arthritis "IBD"
6-Adult still's disease.

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•Gingival overgrowth is a common side effect of phenytoin.

Other causes:
-Anticonvulsants (such as phenytoin, phenobarbital, vigabatrin, ethosuximide, topiramate and primodone NOT common for valproate)
-Calcium channel blockers (antihypertensives such as nifedipine, amlodipine, and verapamil).
-The dihydropyridine derivative isradipidine can replace nifedipine and does not induce gingival overgrowth.
-Cyclosporine, an immunosuppressant.

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-Acute promyelocytic leukemia (APL) has the highest curability.

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•Imatinib

-In ALL and CML with philadelphia chromosome.

-Common side effects include vomiting, diarrhea, muscle pain, headache, and rash. Severe side effects may include fluid retention, gastrointestinal bleeding, bone marrow suppression, liver problems, and heart failure.
-Use during pregnancy may result in harm to the fetus.

-Imatinib works by stopping the Bcr-Abl tyrosine-kinase.
-This can slow growth or result in programmed cell death of certain types of cancer cells.

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•Blast crisis is the cause of death in the majority of patients with CML.

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•What are the myeloproliferative disorder?

Group of disease consisting of:

-Chronic myelocytic leukemia
-Myelofibrosis
-Polycythemia rubra vera
-Essential thrombocythemia.

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-Chronic lymphocytic leukaemia (CLL) is the most common variety of leukaemia. And the most benign.

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