TNF-alpha inhibitors are known to ameliorate the symptoms and disease activity of Arthritis mutilans (a rare and severe form of psoriatic arthritis), by disabling the cytokines that are involved in inflammation and joint destruction. From the mentioned choices, this would be the most effective option. Methotrexate is the most commonly used DMARD, followed by sulfasalazine used in mild to moderate forms of psoriatic arthritis but has not shown much efficacy in arthritis mutilans. Phototherapy, narrowband UVB light therapy can be very effective in clearing skin lesions.

Bombesin is a tumour marker elevated in small cell lung carcinomas, as well as in gastric carcinomas and retinoblastomas.

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)

Carbon monoxide (CO) is a colourless, odourless gas produced by incomplete combustion of carbonaceous material. Clinical presentation in patients with CO poisoning ranges from headache and dizziness to coma and death. Hyperbaric oxygen therapy can significantly reduce the morbidity of CO poisoning, but a portion of survivors still suffer significant long-term neurologic and affective sequelae.

Complaints:
Malaise, flulike symptoms, fatigue
Dyspnoea on exertion
Chest pain, palpitations
Lethargy
Confusion
Depression
Impulsiveness
Distractibility
Hallucination, confabulation
Agitation
Nausea, vomiting, diarrhoea
Abdominal pain
Headache, drowsiness
Dizziness, weakness, confusion
Visual disturbance, syncope, seizure
Faecal and urinary incontinence
Memory and gait disturbances
Bizarre neurologic symptoms, coma

Vital signs may include the following:
Tachycardia
Hypertension or hypotension
Hyperthermia
Marked tachypnoea (rare; severe intoxication often associated with mild or no tachypnoea)
Although so-called cherry-red skin has traditionally been considered a sign of CO poisoning, it is in fact rare.

The clinical diagnosis of acute carbon monoxide (CO) poisoning should be confirmed by demonstrating an elevated level of carboxyhaemoglobin (HbCO). Either arterial or venous blood can be used for testing. Analysis of HbCO requires direct spectrophotometric measurement in specific blood gas analysers. Elevated CO levels of at least 3–4% in non-smokers and at least 10% in smokers are significant.

Cystic fibrosis (CF) is a multisystemic, autosomal recessive disorder that predominantly affects infants, children, and young adults. CF is the most common life-limiting genetic disorder in whites, with an incidence of 1 case per 3200-3300 new-borns in the United States.

People with CF can have a variety of symptoms, including:
Very salty-tasting skin
Persistent coughing, at times with phlegm
Frequent lung infections including pneumonia or bronchitis
Wheezing or shortness of breath
Poor growth or weight gain in spite of a good appetite
Frequent greasy, bulky stools or difficulty with bowel movements
Male infertility

Signs of bronchiectasis include the tubular shadows; tram tracks, or horizontally oriented bronchi; and the signet-ring sign, which is a vertically oriented bronchus with a luminal airway diameter that is 1.5 times the diameter of the adjacent pulmonary arterial branch.

Bronchiectasis is characterized by parallel, thick, line markings radiating from hila (line tracks) in cylindrical bronchiectasis. Ring shadows represent dilated thick-wall bronchi seen in longitudinal section or on-end or dilated bronchi in varicose bronchiectasis.

Pseudomonas aeruginosa is the key bacterial agent of cystic fibrosis (CF) lung infections, and the most important pathogen in progressive and severe CF lung disease. This opportunistic pathogen can grow and proliferate in patients, and exposure can occur in hospitals and other healthcare settings.

Haemophilus influenzae is regularly involved in chronic lung infections and acute exacerbations of CF patients

The correct course of action after giving terlipressin and resuscitating with IV fluids is to perform an EGD with endoscopic variceal band ligation. According to NICE: ‘Offer endoscopic variceal band ligation for the primary prevention of bleeding for people with cirrhosis who have medium to large oesophageal varices. There are serious complications of a TIPS procedure and it is not the first line treatment.

Nail dystrophy (pitting of nails, onycholysis, subungual hyperkeratosis), dactylitis, sausage shaped fingers are most commonly seen with psoriatic arthropathy. There is asymmetric joint involvement most commonly distal interphalangeal joints. Uveitis and sacroiliitis may also occur. Arthritis mutilans may occur but is very rare. Cutaneous lesions may or may not develop. When they do, its usually much after the symptoms of arthritis.

Among the given options the most appropriate management in this patient would be ethanol and haemodialysis.

Ethanol competes with ethylene glycol for alcohol dehydrogenase and thus, helps manage a patient with ethylene glycol toxicity.

Ethylene glycol is a type of alcohol used as a coolant or antifreeze
Features of toxicity are divided into 3 stages:
Stage 1: (30 min to 12 hours after exposure) Symptoms similar to alcohol intoxication: confusion, slurred speech, dizziness (CNS depression)
Stage 2: (12 – 48 hours after exposure) Metabolic acidosis with a high anion gap and high osmolar gap. Also tachycardia, hypertension
Stage 3: (24 – 72 hours after exposure) Acute renal failure

Management has changed in recent times:
Fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol.
Ethanol has been used for many years works by competing with ethylene glycol for the enzyme alcohol dehydrogenase this limits the formation of toxic metabolites (e.g. glycolaldehyde and glycolic acid) which are responsible for the hemodynamic/metabolic features of poisoning.
Haemodialysis has a role in refractory cases.

This case presents with characteristic symptoms of SLE and with her renal biopsy results of focal glomerulonephritis, this is clearly Class III SLE.

Reverse transcription polymerase chain reaction is a laboratory technique combining reverse transcription of RNA into DNA and amplification of specific DNA targets using polymerase chain reaction. It is primarily used to measure the amount of a specific RNA. The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections.

Clozapine can cause neutropenia or agranulocytosis.

Clozapine is an atypical antipsychotic used in the treatment of schizophrenia, and in patients who are intolerant to, or unresponsive to other antipsychotics.

It is a weak D2-receptor and D1-receptor blocking activity, with noradrenolytic, anticholinergic, and antihistaminic properties.

Many antipsychotic drugs can occasionally cause bone marrow depression, but agranulocytosis is particularly associated with clozapine.

Other side effects include:
Hypotension, tachycardia
Fever, sedation, seizures (with high doses)
Appetite increase
Constipation
Heartburn
Weight gain
Extrapyramidal symptoms
Agranulocytosis
Neuroleptic malignant syndrome

The best next step is to try a dairy-free diet, many patients may develop this in their lifetime. IBS is a diagnosis of exclusion, and one would need to rule lactose intolerance out as a potential aetiology first. She is only 28, and without overt bleeding or signs/sxs/labs suggestive of obstruction or inflammation; colonoscopy, flex sig and a barium enema are not indicated.

There is a strong suspicion of Thrombotic Thrombocytopenic Purpura (TTP) in this patient as he presents with neurological changes (from confusion to convulsions and coma), fever, haemolysis, thrombocytopenia, and renal failure. Additionally, TTP cases may present with jaundice, splenomegaly, and hypertension as seen in this patient. With a diagnosis of TTP, recent studies have shown that platelet transfusion is not recommended in this case because it has been shown to increase the risk for arterial thrombosis and mortality possibly due to increased aggregations.

The chronic asymptomatic carrier state is thought to be why there is continued appearance of the bacterium in human populations. As shedding of the organism is intermittent and sometimes at low levels, methods to detect it have been limited. The Salmonella typhi may be cultured from intestinal secretions, faeces or urine in chronic carriers and is recommended to confirm the diagnosis. Vi agglutination test can also be high in normal people in areas with typhoid endemic. Full blood count or blood culture would not be helpful to determine carrier status. Widal antigen test is unable to differentiate carriers from people with a hx of prior infection.

The best option would be the combination of ampicillin and gentamycin. Changing to IV amoxicillin+gentamycin is however the best among the given choices here.

Old age, persistent backache, weight loss, and osteosclerotic lesions make prostatic adenocarcinoma the most likely diagnosis. The sequelae include severe pain, pathological fractures, hypercalcemia and cord compression. Prostatic adenocarcinoma is detected by elevated levels of prostate specific antigen. Positive serology for borrelia burgdorferi would hint at Lyme disease which does not cause osteosclerotic bone lesions, neither would Neisseria gonorrhoeae have such a presentation.

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 likely diagnosis in this case is Haemolytic Uremic Syndrome (HUS), which is generally seen in young children presenting with a triad of symptoms, namely: acute renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. The typical cause of HUS is ingestion of a strain of Escherichia coli. The laboratory results will usually include fragmented RBCs, decreased serum haptoglobin, reduced platelet count, nonspecific WBC changes, and normal coagulation tests (PTT included).

CXR, blood, and urine tests should be carried out initially to exclude an underlying malignancy. If these are normal, a CT scan of abdomen and pelvis should be arranged as the patient’s age is >40 years. Antiphospholipid antibodies should also be checked for the first unprovoked DVT/PE. There is no history, however, to support an inherited thrombophilia.

The National Institute for Health and Care Excellence (NICE) published guidelines in 2012 for the investigation and management of DVT. If a patient is suspected of having DVT, a two-level DVT Wells score should be used:

DVT likely: 2 points or more
DVT unlikely: 1 point or less

This system of points is based on the following clinical features:
1. Active cancer (treatment ongoing, within six months, or palliative)—1
2. Paralysis, paresis, or recent plaster immobilisation of the lower extremities—1
3. Recently bedridden for three days or more, or major surgery within 12 weeks requiring general or regional anaesthesia—1
4. Localised tenderness along the distribution of the deep venous system—1
5. Entire leg swollen—1
6. Calf swelling at least three cms larger than the asymptomatic side—1
7. Pitting oedema confined to the symptomatic leg—1
8. Collateral superficial veins (non-varicose)—1
9. Previously documented DVT—1
10. An alternative diagnosis is at least as likely as DVT—2

If two points or more—DVT is ‘likely’
If one point or less—DVT is ‘unlikely’

Management

1. LMWH or fondaparinux should be given initially after a DVT is diagnosed.
2. A vitamin K antagonist such as warfarin should be given within 24 hours of the diagnosis.
3. LMWH or fondaparinux should be continued for at least five days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range.
4. Warfarin should be continued for at least three months. At three months, clinicians should assess the risks and benefits of extending the treatment.
5. Consider extending warfarin beyond three months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. This essentially means that if there is no obvious cause or provoking factor (surgery, trauma, significant immobility, etc.), it may be implied that the patient has a tendency to thrombose and should be given treatment longer than the normal of three months. In practice, most clinicians give six months of warfarin for patients with an unprovoked DVT/PE.
6. For patients with active cancer, LMWH should be used for six months.

As both malignancy and thrombophilia are obvious risk factors for DVT, therefore, all patients with unprovoked DVT/PE who are not already known to have cancer should undergo the following investigations:
1. Physical examination (guided by the patient’s full history)
2. Chest X-ray
3. Blood tests (full blood count, serum calcium, and liver function tests) and urinalysis
4. Testing for antiphospholipid antibodies
5. Testing for hereditary thrombophilia in patients who have had unprovoked DVT/PE and have a first-degree relative who has a history of DVT/PE.

Pre-eclampsia is excluded from negative proteinuria. White coat hypertension is excluded with ambulatory blood pressure monitoring. Pregnancy induced hypertension develops after 20 weeks of gestation. So the most likely answer is pre-existing hypertension. She should be investigated for a secondary cause for hypertension.

The most probable cause for diarrhoea is pseudomembranous colitis which is caused by Clostridium difficile. Pseudomembranous colitis is an inflammatory disease of the colon where the antibiotic-induced change in the balance of normal gut flora allows overgrowth of C difficile. Any antibiotic can cause this but the chances are higher with ampicillin, clindamycin, fluoroquinolones, and cephalosporins.

Assess the need for oxygen therapy in people with:
– very severe airflow obstruction (FEV1 below 30% predicted)
– cyanosis (blue tint to skin)
– polycythaemia
– peripheral oedema (swelling)
– a raised jugular venous pressure
– oxygen saturations of 92% or less breathing air.

Also consider assessment for people with severe airflow obstruction (FEV1 30–49% predicted).

Consider long-term oxygen therapy for people with COPD who do not smoke and who:
have a partial pressure of oxygen in arterial blood (PaO2) below 7.3 kPa when stable or have a PaO2 above 7.3 and below 8 kPa when stable, if they also have 1 or more of the following:
– secondary polycythaemia
– peripheral oedema
– pulmonary hypertension.

A couple of papers written by the same authors indicate that children and adolescents taking an SSRI definitely experience discontinuation reactions that can be mild, moderate or severe when the medication is stopped suddenly or high doses are reduced substantially. Among the SSRIs paroxetine seems to be the worst offender and fluoxetine the least while sertraline and fluvoxamine tend to be intermediate. The rate of discontinuation syndrome varies with the particular SSRI involved. It is generally quoted as 25% but is higher for SSRIs with shorter half-lives. Paroxetine has been associated with more frequent discontinuation symptoms than the other SSRIs.

The use of fluoxetine with its long half-life appears safer in this respect than paroxetine and venlafaxine causing the most concerns.

Paroxetine has the shortest half-life with 21 hours of all listed SSRIs and as such it would be expected to have a higher incidence or severity (greater number of symptoms) and fluoxetine would have the least since it has a half life of 96 hours. Citalopram has a half-life of 35 hours while escitalopram has a half-life of 30 hours.

The most common symptoms reported are: dizziness, light-headedness, drowsiness, poor concentration, nausea, headache and fatigue.
Another common symptom in adults is paraesthesia described as burning, tingling, numbness or electric shock feelings usually in the upper half of the body or proximal lower limbs.

Again, remember the Hepatitis B serologies: In chronic hepatitis B infection, you have +HBsAg, +anti-HBc, (-)IgM antiHBc, and (-) anti-HBs. In acute hepatitis B infection, you have +HBsAg, + anti-HBc, + IgM anti-HBc, and negative anti-HBs. In immunity due to natural infection, you have negative HBsAg, + anti-HBc, and + anti-HBs. In immunity due to vaccination, you have negative HBsAg, negative anti-HBc, and positive anti-HBs. IN THIS CASE, the person is HBsAg+ for 6 months and everything else is negative, normal transaminase. They do not need antiviral therapy, but their serology should be monitored serially. There would be no reason to do a liver biopsy.

Desmopressin test (done to differentiate nephrogenic diabetes insipidus from central diabetes insipidus), and serum lithium levels can together confirm a diagnosis of lithium-induced nephrogenic diabetes insipidus.

Bipolar disease is most often managed with mood stabilizers like lithium. This patient develops gastrointestinal symptoms followed by an acute confusional state associated with polyuria and polydipsia. These symptoms are suggestive of diabetes insipidus.

In a case where these symptoms occur in a bipolar patient under treatment, lithium-induced nephrogenic diabetes insipidus should be considered as the most probable cause.

Lithium intoxication can present with symptoms of nausea, vomiting, mental dullness, action tremor, weakness, ataxia, slurred speech, blurred vision, dizziness, especially vertical nystagmus and stupor or coma. Diffuse myoclonic twitching and nephrogenic diabetes insipidus can also occur. Such a clinical syndrome occurs above the serum level of lithium of 1.5–2.0 mEq/L.

Management:
– Correcting electrolyte abnormalities in patients with acute disease is critical and often life-saving.
– Treatment should be initiated with parenteral fluids to replete hypovolemia (normal saline at 200-250 mL/h), followed by administration of hypotonic fluid (0.5% normal saline).
– On the restoration of the volume status of the patient forced diuresis should be initiated by the administration of parenteral furosemide or bumetanide accompanied by continued intravenous hypotonic fluid administration to maintain volume status.
– Polyuria is managed with hydrochlorothiazide combined with amiloride, acetazolamide.

Infection with Klebsiella organisms occurs in the lungs, where they cause destructive changes. Necrosis, inflammation, and haemorrhage occur within lung tissue, sometimes producing a thick, bloody, mucoid sputum described as currant jelly sputum.
The illness typically affects middle-aged and older men with debilitating diseases such as alcoholism, diabetes, or chronic bronchopulmonary disease. An increased tendency exists toward abscess formation, cavitation, empyema, and pleural adhesions.

A t test is a type of statistical test that is used to compare the means of two groups. It is one of the most widely used statistical hypothesis tests in pain studies. There are two types of statistical inferences: parametric and nonparametric methods. Parametric methods refer to a statistical technique in which one defines the probability distribution of probability variables and makes inferences about the parameters of the distribution. In cases in which the probability distribution cannot be defined, nonparametric methods are employed. T tests are a type of parametric method; they can be used when the samples satisfy the conditions of normality, equal variance, and independence. In this case the data is parametric, and they belong to the same patients, so a paired t test should be used.

This is most likely describing irritable bowel syndrome (IBS). Symptoms are either diarrhoea, constipation, or both, abdominal pain, bloating, with various durations. It is a functional, not organic, problem, as far as research shows at this point. It is essentially a diagnosis of exclusion. Treatment is a high fibre diet with fluids. Caffeine should be avoided as this can worsen symptoms. Full colonoscopy is not warranted at this time, neither is a barium enema. A wheat-free diet is not likely to help as there is no evidence they have an allergy to this.

Type 1 diabetes is a chronic illness characterized by the body’s inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas. Approximately 95% of patients with type 1 DM have either HLA-DR3 or HLA-DR4. Although the genetic aspect of type 1 DM is complex, with multiple genes involved, there is a high sibling relative risk. Whereas dizygotic twins have a 5-6% concordance rate for type 1 DM, monozygotic twins will share this diagnosis more than 50% of the time by the age of 40 years.

In adult practice, biochemical analysis of pleural fluid plays an important part in the management of pleural effusions. Protein levels or Light’s criteria differentiate exudates from transudates, while infection is indicated by pleural acidosis associated with raised LDH and low glucose levels. In terms of treatment, the pH may even guide the need for tube drainage, suggested by pH <7.2 in an infected effusion, although the absolute protein values are of no value in determining the likelihood of spontaneous resolution or chest drain requirements. pH is therefore the most important factor.

Catatonia is a state of apparent unresponsiveness to external stimuli and apparent inability to move normally in a person who is apparently awake. Catatonia can be acute and occur in severely ill patients with underlying psychiatric or other medical disorders.

A history of behavioural responses to others usually includes the presence of the following:
– Mutism (absence of speech)
– Negativism (performing actions contrary to the commands of the examiner)
– Echopraxia (repeating the movements of others)
– Echolalia (repeating the words of others)
– Waxy flexibility (slight, even resistance to positioning by examiner)
– Withdrawal (absence of responses to the environment).

In the presence of a catatonic state, both first and second generation antipsychotics (SGA) may contribute to maintaining or worsening the catatonic state and increase the risk of developing NMS (neuroleptic malignant syndrome).

Electroconvulsive therapy (ECT) is effective in all forms of catatonia, even after pharmacotherapy with benzodiazepines has failed. Response rate ranges from 80% to 100% and results superior to those of any other therapy in psychiatry. ECT should be considered first-line treatment in patients with malignant catatonia, neuroleptic malignant syndrome, delirious mania or severe catatonic excitement, and in general in all catatonic patients that are refractory or partially responsive to benzodiazepines. Early intervention with ECT is encouraged to avoid undue deterioration of the patient’s medical condition.

Electroconvulsive therapy (ECT) is a procedure, done under general anaesthesia, in which small electric currents are passed through the brain, intentionally triggering a brief seizure. ECT seems to cause changes in brain chemistry that can quickly reverse symptoms of certain mental health conditions.