Saturday, January 7, 2017

What are the drugs cause pulmonary fibrosis?

What are the drugs cause pulmonary fibrosis?

The Following drugs are responsible for development of pulmonary fibrosis/Lung fibrosis:

  • Cyclophophamide
  • Busulphan
  • Methysergide
  • Amiodarone
  • Methotrexate
  • Nitrofurantoin
  • Minocycline
  • Ethambutal
  • Penicillamine

What are Cyclophosphamide induced lung injuries?

Lungs injury or damage by cyclophosphamide are followings:

It causes mainly two diseases:

1. Cyclophosphamide induced lung fibrosis:

  • Genetic factors play important role in developing fibrosis in lung after exposure to the drug
  • Fibrosis is relentlessly progressive and inevitably turns into terminal respiratory failure.
  • X ray shows reticulo-nodular shadow in upper zone.
  • No effective treatment and no change after cessation of the drug after starting of the disease process

2. Acute pneumonitis due to the drug:

  • It usually present with cough, dyspnea, hypoxia and bilateral nodular opacity in upper zone.
  • It responds to cessation of drug and to corticosteroid therapy.

 

Lung injury takes place due to toxic metabolites of cyclophosphamide. Those are:

  • Hydroxycyclophosphamide
  • Acrolein
  • Phsophoramide mustard

What is Primary Sclerosing Cholangitis?

PSC(Primary Sclerosing Cholangitis) is a biliary disease of unknown cause, but characterized by immunological destruction of intra and extre hepatic biliary ducts.

Association of PSC:

  • Inflammatory bowel disease: 90% of the patient with PSC is associated with IBD particularly UC, lesser extent with Crohn’s disease. The frequency of PSC is inversely proportional to the severity of UC. (Note: 4% of patients with UC have PSC)
  • HIV
  • Coeliac disease

Clinical features of PSC:

  • May be asymptomatic
  • Fatigue
  • Intermittent jaundice
  • Pruritus
  • Features of cholestatis
  • Right upper abdominal pain
  • Hepatomegally

Complications of PSC:

  • Chronic cholestasis
  • Statorrhoea
  • Fat solubale vitamin malabsorption
  • Large biliary stricture
  • Cholangitis
  • Cholangiocarcinoma
  • Colonic carcinoma

Investigations of PSC:

  • ERCP is gold standard to confirm the disease. It shows multiple biliary strictures which gives rise to a ‘beaded’ appearance
  • Liver biochemistry: Liver markers are raised but alkaline phosphatase is greater than transaminase
  • MRCP
  • ANCA may be positive
  • Biopsy: has limited role but it may shows fibrosis, obliterative cholangitis, described as ‘onion skin’

Primary sclerosing cholangitis

Management:

  • No effective treatment to halt the progression of the disease
  • Cholestyramine for pruritus
  • Fat soluble vitamin supplementation
  • Antibiotic prophylaxis before or during instrumentation to prevent cholangitis (Ciprofloxacin is the drug of choice here)
  • Biliary stenting (improve liver biochemistry and symptoms)
  • Definitive treatment: Liver transplantation (Post transplantation survival rate is 90%)

 

Indication of liver transplantation in PSC:

  • Biliburin> 100 µmol/l
  • Recurrent cholangitis
  • Ascitis
  • Refractory itching

But cholangiocarcinoma is a contraindication for transplantation.

Thursday, December 22, 2016

What is Coeliac disease?

Coeliac disease:

Coeliac disease is a disorder characterized by total villous atrophy in small intestine as a result of glutein containing food.

Mechanism of damage:

Small bowel damage or injury occurs as a result of glutein ingestion. Glutein is high molecular weight compound which contains various gliadins. α-gliadin damage small bowel mucosa in these patient through immune mediated mechanism.

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Genetics of coeliac disease:

It has strong association with-

  • HLA- DQ2 (95% of the patients)
  • HLA- B8 (80%)
  • HLA- DR3
  • HLA-DR7
  • HLA-DQW2

But non-genetic factors can also be responsible as there is 30% disconcordance among the identical twins.

What are the other diseases associated with Coeliac disease?

  • Insulin-dependent diabetes mellitus (2–8%)
  • Thyroid disease (5%)
  • Primary biliary cirrhosis(3%)
  • Sjögren’s syndrome (3%)
  • IgA deficiency (2%)
  • Pernicious anaemia
  • Sarcoidosis
  • Neurological complications: encephalopathy, cerebellar atrophy, peripheral neuropathy, epilepsy
  • Myasthenia gravis
  • Dermatitis herpetiformis
  • Down’s syndrome
  • Enteropathy-associated T-cell lymphoma
  • Small bowel carcinoma
  • Squamous carcinoma of oesophagus
  • Ulcerative jejunitis
  • Pancreatic insufficiency
  • Microscopic colitis
  • Splenic atrophy

Foods concerned with Coeliac disease:

Glutein containing cereals:

  • Wheat: bread, pasta, pastry
  • Barley: beer (whisky is made from malted barley. Glutein is however removed during distillation process. So that it is safe to drink for the patient with coeliac disease)
  • Rye
  • Oats (some coeliac disease patient can tolerate these)

Some notable glutein free food:

  • Rice
  • Potatoes
  • Corn (maize)

Which patient should be screened for coeliac disease?

If a patient is manifesting following signs and symptoms:

  • Chronic or intermittent diarrhea
  • Failure to thrive or faltering growth (in children)
  • Persistent or unexplained gastrointestinal symptoms including nausea and vomiting
  • Prolonged fatigue (‘tired all the time’)
  • Recurrent abdominal pain, cramping or distension
  • Sudden or unexpected weight loss
  • Unexplained iron-deficiency anemia or other unspecified anemia
  • Recurrent mouth ulcers

If a patient has following existing diseases:

  • Autoimmune thyroid disease
  • Dermatitis herpetiformis
  • Irritable bowel syndrome
  • Type 1 diabetes
  • First-degree relatives (parents, siblings or children) with coeliac disease

What are the clinical features of coeliac disease?

Clinical features of coeliac disease vary according to age-

In infancy:

  • Usually start after weaning with cereals
  • Diarrhea
  • Malabsorption
  • Failure to thrive

Older child:

  • Usually non-specific symptoms, e.g- Delayed growth
  • Features of malnutrition on examination
  • Mild abdominal distension
  • Growth and puberty delay, leading to short stature in adulthood.

In adult:

  • Usually in 3rd/4th decade
  • Female: male (2:1)
  • Non-specific: Tiredness, weight loss, folate or iron deficiency
  • Florid malabsorption
  • Oral ulcer, dyspepsia, bloating
  • May present with complications (see below)

What are the complications of coeliac disease?

  • Anemia: iron, folate and vitamin B12 deficiency (folate deficiency is more common than vitamin B12 deficiency in coeliac disease)
  • Hyposplenism
  • Osteoporosis
  • Lactose intolerance
  • Enteropathy-associated T-cell lymphoma of small intestine
  • Subfertility, unfavourable pregnancy outcomes
  • Rare: esophageal cancer, other malignancies

What are the investigations of coeliac disease?

NICE issued guidelines on the investigation of coeliac disease in 2009. If patients are already taking a gluten-free diet they should be asked, if possible, to reintroduce gluten for at least 6 weeks prior to testing.

Investigations of coeliac disease can be divided in following categories:

A. Biopsy and histopathology of the specimen

  • Specimen are endoscopically taken from second part of duodenum (D2) or jejunum
  • Possible findings:
    • Villous atrophy
    • Crypt hyperplasia
    • Increase intraepithelial lymphocytes
    • Lamina propria infiltration with lymphocy

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B. Immunological test:

  • Tissue transglutaminase (TTG) antibodies (IgA) are first-choice according to NICE
  • Endomyseal antibody (IgA): Are detectable by immunofluorescence in most untreated cases. They are sensitive (85–95%) and specific (approximately 99%) for the diagnosis, except in very young infants
  • Anti-gliadin antibody (IgA or IgG) tests
  • Anti-casein antibodies are also found in some patients

C. Other tests:

  • Haematology:
    • CBC ( it may show microcytic or macrocytic anaemia from iron or folate deficiency respectively.
    • Features of hyposplenism may be present (target cells, spherocytes and Howell– Jolly bodies
  • Biochemistry: Biochemical tests may reveal reduced concentrations of calcium, magnesium, total protein, albumin or vitamin D.
  • Measurement of bone density should be considered to look for evidence of osteoporosis, especially in older patients and post-menopausal women.

Management of Coeliac disease:

  • Lifelong gluten free diet
  • Correct existing deficiencies of iron, folate, calcium and/or vitamin D

Tuesday, December 13, 2016

Churg-Strauss syndrome (CSS)

What is Churg-Strauss syndrome (CSS)?

Churg-Strauss syndrome is a small vessel multi-system vasculitis characterized by cutaneous vasculitic lesions, eosinophilia (usually < 2.0×109/l), asthma (usually mild), mononeuritis or polyneuropathy and rarely glomerulonephritis (10% cases). Gastrointestinal and cardiac involvements are also recognized.

Clinical features of Churg-Strauss syndrome:

  • Pulmonary: Pulmonary findings dominate the clinical presentation with paroxysmal asthma attacks and presence of fleeting pulmonary infiltrates. Asthma is the cardinal feature and may be present for years before overt features of multi system vasculitis become apparent.
  • Cutaneous: Skin lesions include purpura and cutaneous and subcutaneous nodules; occur in up to 70% of patients.
  • GIT: Gastrointestinal complications include mesenteric ischemia and gastrointestinal bleeding
  • Cardiac: Cardiac involvement is characterized by myo-pericarditis.
  • Renal: Glomerulonephritis

Diagnosis of Churg-Strauss syndrome:

  • Mostly clinical
  • Serum ANCA ( MPO subset are elevated but non-specific)
  • Biopsy and histopathology: Necrotizing granulomatous vasculitis with extravascular eosinophilic infiltration on lung, renal or sural biopsy.

Prognosis of Churg-Strauss syndrome:

  • Poor, without treatment.
  • 5 year survival rate is 25% only
  • With treatment this survival rate may increase to more than 50%

Treatment of Churg-Strauss syndrome:

  • Corticosteroids
  • Cyclophosphamide and prednisolone (in patient with acute vasculitis)

 

Additional questions:

 

What are the phase of Churg-Strauss syndrome?

This syndrome passes through 3 phases:

1. The prodromal phase, which may be present for years and comprises of rhinitis, nasal polyposis and frequently asthma

2. The eosinophilic phase, which can remit and recur for years. It is characterized by the onset of peripheral blood and tissue eosinophilia, resembling Loeffler’s syndrome, chronic eosinophilic pneumonia or eosinophilic gastroenteritis.

3. The vasculitic phase, which usually occurs in the third or fourth decade of life and is characterized by a life threatening systemic vasculitis of small and occasionally medium sized vessels. This phase is associated with constitutional symptoms and signs, fever and weight loss.

 

What are the diagnostic criteria of Churg-Strauss Syndrome?

American college of Rheumatology 1990 criteria for Churg-Strauss syndrome:

The presence of 4 or more of the manifestations below is highly indicative of Churg-Strauss syndrome:

  • Asthma
  • Eosinophilia (10% on WCC differential)
  • Mononeuropathy or polyneuropathy
  • Migratory or transient pulmonary infiltrates
  • Systemic vasculitis (cardiac, renal, hepatic)
  • Extravascular eosinophils on a biopsy including artery, arteriole or venule.

What are the causes of renal failure and eosinophilia?

  • Rapidly progressive glomerulonephritis
  • CSS
  • Acute tubule-interstitial nephritis
  • Cholesterol micro-emboli

Monday, December 12, 2016

What is malabsorption syndrome?

Malabsorption syndrome: 

Malabsorption syndrome includes various clinical conditions related with gastrointestinal tract such as chronic diarrhea, steatorrhoea, abdominal distension and weight loss.

What are the causes of malabsorption syndrome?

Malabsorption syndrome happens in following disease conditions of intestinal tract (Mostly in small intestine).  Some distinguishing features of each cause are mentioned below:
  • Coeliac disease:  High antigliadin or antireticulin antibodies. Antiendomyosium antibodies are highly specific.
  • Dermatitis herpetiformis: Gluten-sensitive enteropathy. Associated with subepidermal blistering rash.
  • Bacterial overgrowth: Low B12 but normal or high folate. Previous gastric surgery (Billroth II), jejunal diverticuli.
  • Giardiasis: May be detected on stool microscopy. Patient may Travel abroad or may be immunosuppressed.
  • Whipple’s disease: Associated locomotor/neurological/ cardiac features. HLA B27 positive. PAS positive macrophages which contain the bacillus Tropheryma whipelli on small bowel biopsy.
  • Tropical sprue: History of living in an endemic area for over 3 months
  • Radiation enteritis:  Previous history of abdominal irradiation.
  • Crohn’s disease:  Abdominal pain/ diarrhea predominate. May have isolated B12 deficiency which is not corrected with intrinsic factor.
  • Hypogammaglobulinaemia: Very similar to cystic fibrosis. Gut, respiratory and locomotor involvement. Low globulins. Giardia infections common
  • Zollinger-Ellison Syndrome:  History of recurrent peptic ulceration predominates.
  • Intestinal lymphangiectasia: Hypoproteinaemia as a result of protein-losing enteropathy and steatorrhoea. Associated immunoglobulin deficiency. Congenital dilatation of small bowel lymphatics. May occur secondary to pericardial constriction or severe heart failure. Primary lymphatic abnormalities elsewhere may lead to chylous pleural effusions and chylous ascities.