Churg-Strauss disease (CSD) is one of three important fibrinoid, necrotizing, inflammatory leukocytoclastic systemic small-vessel vasculitides that are associated with antineutrophil cytoplasm antibodies (ANCAs).
The first (prodromal) phase of Churg-Strauss disease (CSD) consists of asthma usually in association with other typical allergic features, which may include eosinophilia. During the second phase, the eosinophilia is characteristic (see below) and ANCAs with perinuclear staining pattern (pANCAs) are detected. The treatment would therefore be different from asthma. For most patients, especially those patients with evidence of active vasculitis, treatment with corticosteroids and immunosuppressive agents (cyclophosphamide) is considered first-line therapy

The given history is more compatible with spontaneous pneumothorax. Left-sided pneumothoraxes may be associated with a clicking noise, which is heard with each heart-beat and can sometimes be heard by the patient.

Computed tomographic pulmonary angiography (CTPA) is the standard investigative tool, used for diagnosing a pulmonary embolism. Pulmonary angiography is indicated if CTPA is not available.

Sildenafil citrate (Viagra) is the first oral drug to be widely approved for the treatment of erectile dysfunction.
It is a potent and selective inhibitor of type-V phosphodiesterase, the primary form of the enzyme found in human penile erectile tissue, thereby preventing the breakdown of cyclic guanosine monophosphate (cGMP), the intracellular second messenger of nitric oxide.

Uses:
It is used for the treatment of erectile dysfunction, idiopathic pulmonary hypertension, premature ejaculation, high altitude illness, penile rehabilitation after radical prostatectomy, angina pectoris, and lower urinary tract symptoms.

Adverse effects:
Mild headache, flushing, dyspepsia, cyanopsia, back pain, and myalgias – due to a high concentration of PDE11 enzyme in skeletal muscle, which shows significant cross-reactivity with the use of tadalafil.
It can also cause hypotension, dizziness, and rhinitis.

Giardiasis also known as travellers diarrhoea is caused by Giardia lamblia, which is an anaerobic parasite affecting the small intestine. It can lead to diarrhoea, flatulence, abdominal cramps, malodourous greasy stools and intestinal malabsorption. It can also cause bloody diarrhoea. The investigation of choice is stool examination for trophozoites and cysts. It is treated by metronidazole and tinidazole as first line therapies.

The skin lesion is most probably eczema. It is common among atopic people. Asthma is a common association.

Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination.

Smoking cessation is the most effective intervention in stopping the progression of COPD, as well as increasing survival and reducing morbidity. This is why smoking cessation should be the top priority in the treatment of COPD. Long term oxygen therapy (LTOT) may increase survival in hypoxic patients. The rest of the options dilate airways, reduce inflammation and thereby improve symptoms but do not necessarily increase survival.

There are many possible causes of a red eye. It is important to be able to recognise the causes which require urgent referral to an ophthalmologist. Acute angle closure glaucoma presents with severe pain, decreased visual acuity, patient seeing haloes, semi-dilated pupils, and hazy cornea. Anterior uveitis presents with acute onset pain, blurred vision and photophobia, with small, fixed oval pupils and ciliary flush.

Anti-TNF-α therapy is effective for patients with arthritis but it can oftentimes lead to the reactivation of latent TB. Hence it should be used with great caution in patients with a past history of TB or current infection.

The patient has Meigs syndrome. Meigs syndrome is defined as a triad of benign ovarian tumour with ascites and pleural effusion that resolves after resection of the tumour. Ovarian fibromas constitute the majority of the benign tumours seen in Meigs syndrome.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

The patient has small cell lung cancer presented by paraneoplastic syndrome; Ectopic ACTH secretion.

Small cell lung cancer (SCLC), previously known as oat cell carcinoma is a neuroendocrine carcinoma that exhibits aggressive behaviour, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and a frequent association with distinct paraneoplastic syndromes.
Common presenting signs and symptoms of the disease, which very often occur in advanced-stage disease, include the following:
– Shortness of breath
– Cough
– Bone pain
– Weight loss
– Fatigue
– Neurologic dysfunction
Most patients with this disease present with a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
SIADH is present in 15% of the patients and Ectopic secretion of ACTH is present in 2-5% of the patients leading to ectopic Cushing’s syndrome.

The presentation of the patient is typical of chronic lithium toxicity (due to the presence of mainly neurological manifestations). Additional to the blood investigations mentioned, urine analysis, electrolyte levels, and renal function should also be performed. A low urine Anion gap and a low urine specific gravity are highly suggestive of lithium toxicity.
ECG obtained in this patient is likely to show: nonspecific, diffuse ST segment depression with T wave inversion.
Acute lithium toxicity presents with more GI manifestations while, the clinical features of chronic lithium toxicity are mainly neurological and can include:
Coarse tremors (fine tremors are seen in therapeutic levels), hyperreflexia, acute confusion, seizures, and coma.
The management of lithium toxicity is as follows:
Immediate GI decontamination with gastric lavage (in case of acute intoxication)
Saline Administrations: the goal of saline administration is to restore GFR, normalize urine output and enhance lithium clearance.
Haemodialysis remains the mainstay treatment for lithium toxicity as lithium is readily dialyzed because of water solubility, low volume of distribution, and lack of protein binding.
The Extracorporeal Treatments in Poisoning Workgroup (EXTRIP Workgroup) recommendations for dialysis (extracorporeal treatment) in lithium toxicity include:
• Impaired kidney function and lithium levels > 4.0 mEq/L
• Decreased consciousness, seizures, or life-threatening dysrhythmias, regardless of lithium levels
• Levels are > 5.0 mEq/L, significant confusion is noted, or the expected time to reduce levels to < 1.0 mEq/L is more than 36 hours
As post-dialysis rebound elevations in lithium levels have been documented, continuous veno-venous hemofiltration (CVVH) has been advocated.

Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless oedema, but oedema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule.

Intestinal phosphate absorption is mediated by both transcellular and paracellular routes. The 1,25(OH)2D increases intestinal transcellular phosphate absorption at least in part by enhancing expression of type 2b sodium–phosphate cotransporter, thus increasing plasma phosphate.

Bicarbonate therapy is not indicated in mild and moderate forms of DKA because metabolic acidosis will correct with insulin therapy. The use of bicarbonate in severe DKA is controversial due to a lack of prospective randomized studies. It is thought that the administration of bicarbonate may actually result in peripheral hypoxemia, worsening of hypokalaemia, paradoxical central nervous system acidosis, cerebral oedema in children and young adults, and an increase in intracellular acidosis. Because severe acidosis is associated with worse clinical outcomes and can lead to impairment in sensorium and deterioration of myocardial contractility, bicarbonate therapy may be indicated if the pH is 6.9 or less.

1B: Individual Randomised Control Trial (with narrow confidence intervals)

The main symptom of dermatomyositis include skin rash and symmetric proximal muscle weakness (in over 90% of patients) which may be accompanied by pain and tenderness. It occurs more commonly in females. Skin findings include:
Gottron’s sign – an erythematous, scaly eruption occurring in symmetric fashion over the MCP and interphalangeal joints
Heliotrope or lilac rash – a violaceous eruption on the upper eyelids and in rare cases on the lower eyelids as well, often with itching and swelling
Shawl (or V-) sign is a diffuse, flat, erythematous lesion over the back and shoulders or in a V over the posterior neck and back or neck and upper chest, which worsens with UV light.
Erythroderma is a flat, erythematous lesion similar to the shawl sign but located in other areas, such as the malar region and the forehead.
Periungual telangiectasias and erythema occur.

The oxygen saturation in the pulmonary artery is higher than that of the right ventricle. The pressure of the pulmonary artery and of the PCWP are also high. So patent ductus arteriosus is highly suggestive.

Drug induced lupus is usually positive for antinuclear and antihistone antibodies, typically without renal or neurologic involvement. However, pulmonary involvement is common. Drugs that can induce lupus include isoniazid, hydralazine, procainamide, chlorpromazine, and other anticonvulsants.