Psoriasis

Definition
                -is a chronic non-infectious inflammatory dematosis characterized by well demarcated erythematous plaques topped by silvery scales.

Epidemiology
-1.5-3% of population in Europe and North America
-Sex incidence is equal
-Peak age: 20s, 30s and 60s.
-may start at any age but unusual in children <8 years.

Aetiopathogenesis
-Genetics:
               -35% of patients show family history.
               -if one parent affected, probability-25%
               -if both parents affected, probability increases up to

Osteoporosis

Definition
                     It's a disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and an increase in fracture risk.

Pathogenesis
                      -increased bone breakdown by osteoclasts
                      -decreased bone formation by osteoblasts.
Therefore, loss of bone mass.
The bone mass decreases with age but depends on the Peak mass attained

Nephritic Syndrome by S.Wangdi

-mainly glomerulus affected.
-podocytes defective
                     
-Clinical  features:
                 1.haematuria-rbc casts
                 2.hypertension
                 3.proteinuria<3.5g/24hr
                 4.Oliguria <400ml/day
                 5.uraemia
                 6.azotaemia

Diagnosis
             .-Anti-streptolysin O titre/ASO titre(for post streptoccal infection only)
              -renal biopsy 
                                -focal--IgA nephropathy, Alport syndrome(hereditary nephritits, henoch scholein purpura, SLE,
                                -diffused
                                             -membranoproliferative, rapidly

Rhabdomyolysis by T.Uden.

What is it?
          -a syndrome of skeletal muscle injury releasing toxic intracellular material into the blood circulation causing signs and symptoms.

Triads:
        -myalgia
        -dark urine
         -muscle weakness

-children-myalgia nad generalised weakness

Complications- DIC and renal failure

Diagnosis by:
                    -Lab test:
                               -increased plasma CK 4-5 fold elevated.
                               -myoglobin in the urine.

Managment:
     -correction of fluid and electrolytes.
     -treat the underlying causes.

Pathophysiology:
                          -an increase in intracellular free ionized calcium

Osteomalacia by T.Pem.

In osteomalacia
                   -Demineralization of bone. 
                                                    -i.e hydroxyapatite which forms 90% of bone mineral is reduced.
In rickets-undermineralization.
causes:
         vit D deficiency.
                              - a hormone
                                   7-dehydrocholesterol----->cholecalciferol----->25OHD3(liver)---->1,25OH calciferol--rate limiting step(controled by PTH.(active-calcitriol) or 1 24-OH calciferol(inactive)

Functions.--maintain calcium level in the body.

1.calcium absorption from GIT.
2.reduces calcium excretion in kidney.
3.increases bone mineralization.(90% of calcium in bone.

DMARDs.(Disease Modifying Anti-Rheumatoid Drugs)


-25% recover completely
-continue more or less normal life with drug therapy.

Drug Therapy.

.Analgesia and NSAIDs
                                     -mainly for symptoms control.

.Cortocosteroids.
                          -slows down the progress of the disease.(immunosupressants)
                          -intra-articular injections and i.m. depot injections.

.Disease Modifying Anti-Rheumatoid Drugs.(DMARDs)

Traditional DMARDs.
                       
 "Most Sufferers Can Get Appropriate Pain Control...Lol ".

M-methotrexate
S-sulfasalazine
C-ciclosporin
G-gold
A-azathioprine.
P-penicillamine
C-hydroxyChloroquine
L-leflunomide


Biological DMARDs. 

-genetically  engineered drugs – meaning that human genes that normally guide the production of these natural human immune proteins (i.e., an antibody to TNF) are used in non-human cell cultures to produce large amounts of a biologic drug.

-In these diseases, TNF or IL-1 act to increase inflammation, similar to the effect of gasoline on a fire.
-However, in rheumatoid arthritis TNF or IL-1 (the gasoline) acts to excite the inflamed joint (the fire).

-are very expensive
-so, they are used after at least 2 traditional DMARDs usually methotrexate and sulfasalazine.

1.TNF-alpha inhibitors.
                 -etanercept
                                  -fully humanized p75 TNF-alphareceptor IgG1.
                                  -25 mg 2 weekly or 50mg weekly, s.c
                                 -Given S.C  and self-administration.
                                  -65% of patients respond well.
                 -adalimumab
                                  -s.c 40mg alternate week
                                  -fully humanized monoclonal antibody against TNF-alpha given along with methotrexate.
                  -infliximab
                                 -i.v. 3-10mg/kg every 4-8 weeks.
                                  -a monoclonal antibody against TNF-alpha
                                  -co-prescribed with methotrexate
                                  -given intravenously.

*These drugs slow or halt erosion formation upto 70% of patients with RA and produce healing in few.
*Chances of secondary failure, 50% with infliximab and less with etanercept and adalimumab.

Side Effects:
                -Increased tumour development is controversial.
                -ANA positive in few--->SLE, Leucocytoclastic vasculities, extracutaneous involvement or sinterstitial lung disease
                -Reactivation of old TB, therefore pre-treatment chest x-ray recommended.
                -increased risk of infection, so close monitoring required.

2.Cytokine IL-1 inhibitor.
                                        -Anakinra
                                                      -a human recombinant IL-1 receptor antagonist.
                                                      -used along with methotrexate
                                                      -used after anti-TNF agents failure.

3.Others.
             1.Rituximab
                               - a monoclonal Ab
                               -lysis of CD-positive B cells.
             2.Abatacept
                               -modulates T cells activation.
             3.Tocilizumab
                                -Anti-IL-6 receptor (clinically in trials now)

Drugs Used Less Commonly.

            1.Gold- sodium aurothiomalate by deep I.M. injection
            2.Hydroxychloroquine.- anti-malarial
                                               -200-400mg daily alone in mild disease or as an adjunct to DMARDs.
                                               -retinopathy is side effect.
           3.Penicillamine-125g daily for 1 month and 500-750g daily before food for at least 3 months before improvement occurs.
                                 -if proteinuria exceeds >2g/24h, it should be stopped.
                                 -SLE and myasthenia gravis like syndrome occurs.
           4.Azathioprine- max. dose of 2.5mg/kg and cyclophosphamide 1-2mg/kg usually when DMARDs are ineffective.
            5.Ciclosporin
                               -2.5-4mg.kg
                               -used for active RA.
                               -s.e- hypertension and rise in creatinine level.






Infective Endocarditis

-It is an endovascular infection of cardiovascular structures including cardiac valves, atrial and ventricular endocardium, large intrathoracic vessels and intracardiac foreign bodies, e.g. prosthetic valves, pacemaker leads and surgical conduits.

-It's more common in the developing countries.
-Mortality rate equals to 100% without treatment.

Aetiology- is a consequence of two abnormal factors.

1.Bacteraemia.
                       -Poor dental hygiene.
                       -I.V. drug use.
                       -Soft tissue infections.
                       -Diagnostic or therapeutic procedures:
                                                                               -dental treatment
                                                                               -intravascular cannulae
                                                                               -cardiac surgery

2.Abnromal cardiac endothelium.
                                                      -Valvular lesions.
                                                      -Septal defects.
                                                      -PDA.(patent ductus arteriosus)
*All these abnormalities promotes platelet and fibrin deposition------>infected vegetation.

*Aortic and mitral valves are the most commonly afftected in I.E. but in I.V. drug users, right-sided lesions are commoner!



Signs and Symptoms:

"FROM JANE"
F-fever
R-roths spot
O-osler's node
M-murmur

J-janeway lesion
A-anaemia
N-nail bed(splinter haemorrhages)
E-emboli.

Diagnostic Criteria: Modified Duke's Criteria

"BE FIVE PM"

Major Criteria


B : Blood culture +ve
  1. Typical micro-organisms in 2 seperate cultures or
  2. Persistently +ve blood cultures drawn 12 hours apart or
  3. Single +ve blood culture for Coxiella burnetti
E : Endocardial involvement
  1. +ve echocardiogram (vegetation, abscess or valve dehiscence) or
  2. New valvular regurgitation
Minor criteria
  1. Fever > 38 oC 
  2. Immunologic phenomena (glomerulonephritis, Osler’s nodes, Roth’s spots, Rheumatoid factor)
  3. Vascular phenomena (major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunCtival hemorrhage, Janeway lesions)
  4. Echocardiography findings (suggestive but not definitive)
  5. Predisposition (heart condition or IV drug user) 
  6. Microbiologic evidence (Positive blood culture but not meeting major criteria)

*Definitive Diagnosis requires 2 Major  or 3 Minor + 1 Major or  5 Minor




Hirsutism.

Definition.

-Excessive hair growth in a male pattern.
-Androgen dependent

Common areas involved:
                      -Beard
                      -Abdominal wall
                      -Thighs
                      -Around nipples

Causes:

            -Idiopathic
            -Polycystic ovarian syndrome(PCOS)
            -Others(2%):
                               -congenital hyperplasia of adrenal glands.
                               -prolactinoma
                               -ovarian/adrenal tumours
                               -acromegaly

*Hirsutism must be well differentiated from Hypertrichosis while making a diagnosis.

              Hypertrichosis
                                      -General increase in body hair.

Causes:
           -Drugs: ciclosporin, phenytoin, minoxidil.
           -Systemic illness: hypothyrodism, undernutrition.

             Polycystic Ovarian Syndrome.
                                      -multiple small cysts in the ovary.
                                      -excess androgens production, mainly from ovaries.
                                      -cyst: is an arrested follicle of its development.
                                      -anovulation.
                                      -insulin resistance.
                                      -hypertension
                                      -hyperlipidaemia

Clinical features:
              -amenorrhoea/oligomenorrhoea
              -hirsutism
              -acne
              -marked obesity (rare)
              -mild virilization (in severe case)

* Diagnosis is usually made Clinically but following investigations also support the diagnosis:
                                          -elevated serum testosterone.
                                          -normal/elevated LH
                                          -normal FSH
                                          -multiple ovarian cysts (USS)

              Management of Hirsutism.
                                         -Excess hair removal:
                                                                        -shaving.
                                                                        -bleaching.
                                                                        -waxing.
                                        -Drugs:
                                                   -Cyproterone(antiandrogenic.)
                                                   -Oestrogen(reduces free androgens)
                                                   -Spironolactone(antiandrogenic)
                                                   -Finasteride(5-alpha-reductase inhibitor)

*But in cases like:
                         -who are concerned about their fertility: Clomifene(anti-oestrogen)
                         -"        " not "                  "           "       :OCPs-to manage menstrual irregularities.
                         --For hyperandrogenic signs: Antiandrogenic like cyproterone acetate.