Urinary porphobilinogen is increased between attacks of acute intermittent porphyria (AIP) and even more so, between acute attacks.

AIP is a rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. This results in the toxic accumulation of delta-aminolaevulinic acid and porphobilinogen.

Abdominal and neuropsychiatric symptoms are characteristic of AIP especially in people between the ages of 20–40 years. The disease is more common in females than in males (5:1). Major signs and symptoms of AIP include abdominal pain, vomiting, motor neuropathy, hypertension, tachycardia, and depression.

Diagnosis:
1. Urine turns deep red on standing (classical picture of AIP)
2. Raised urinary porphobilinogen (elevated between attacks and to a greater extent, between acute attacks)
3. Raised serum levels of delta-aminolaevulinic acid and porphobilinogen
4. Assay of red blood cells for porphobilinogen deaminase

The NICE 2017 guidelines state that in patients who are uncontrolled with a SABA (Salbutamol) and ICS (Inhaled corticosteroid e.g. Beclomethasone), a leukotriene receptor antagonist (LTRA) should be added.
If asthma is uncontrolled in adults (aged 17 and over) on a low dose of ICS as maintenance therapy, offer a leukotriene receptor antagonist (LTRA) in addition to the ICS and review the response to treatment in 4 to 8 weeks.

This recommendation is also stated in NICE 2019 guidelines.

In Wilson’s disease, serum caeruloplasmin is decreased. Skin pigmentation is not increased, but may become jaundiced. 24 hour urine copper excretion is increased. Hepatic copper concentration is increased. Serum copper level is also increased. Key point: high copper. Remember Kayser-Fleisher rings for the eyes in Wilson’s disease.

There are two main reasons for using combinations of chemotherapeutic agents rather than single agents. First, different drugs exert their effects through different mechanisms, therefore, carefully combining them will increase the number of tumour cells killed in each cycle as well as decrease their chances of developing drug resistance. Second, there may be an even greater effect with drugs that are synergistic.

Mania is a state of extreme physical and emotional elation. A person experiencing mania or a manic episode may present with the following symptoms:
-Elevated mood. The person feels extremely ‘high’, happy and full of energy; he or she may describe the experience as feeling on top of the world and invincible. The person may shift rapidly from an elevated,
happy mood to being angry and irritable if they perceive they have been obstructed.
-Increased energy and overactivity. The person may have great difficulty remaining still.
-Reduced need for sleep or food. The person may be too active to eat or sleep.
-Irritability. The person may become angry and irritated with those who disagree with or dismiss his or her sometimes unrealistic plans or ideas.
-Rapid thinking and speech. The person’s thoughts and speech are more rapid than usual.
-Grandiose plans and beliefs. It is quite common for a person in a hypomanic or manic state to believe that he or she is unusually talented or gifted or has special friends in power. For example, the person may believe that he or she is on a special mission from God.
-Lack of insight. A person in a hypomanic or manic state may understand that other people see his or her ideas and actions as inappropriate, reckless or irrational. However, he or she is unlikely to personally accept that the behaviour is inappropriate, due to a lack of insight.
– Distractibility. The person has difficulty maintaining attention and may not be able to filter out external stimuli.

Careful assessment to rule out organic conditions is an important first step in the management of mania. Often hospitalisation is required for someone who is experiencing acute mania. Both mood-stabilising agents such as lithium carbonate or sodium valproate and an antipsychotic may be needed to treat psychotic symptoms, agitation, thought disorder and sleeping difficulties. Benzodiazepines may be useful to reduce hyperactivity. Treatment with lithium alone may have a relatively slow response rate (up to two weeks after a therapeutic blood level is established), so that adjunctive medication such as sodium valproate is usually required. Regular monitoring of blood levels for lithium and valproate is essential because of the potential for toxicity.

The symptoms of hypomania are similar to those of mania: elevated mood, inflated self-esteem, decreased need for sleep, etc. except that they don’t significantly impact a person’s daily function and never include any psychotic symptoms.

Extra-nodal presentation is more common in non-Hodgkin lymphoma (NHL) than in Hodgkin lymphoma (HL). Bone marrow infiltration is more common in low-grade than in high-grade NHLs.

Low-grade NHL is predominantly a disease of older people. Most present with advanced disease, bone marrow infiltration being almost invariable. Anaemia, leucocytosis, and/or thrombocytopaenia in a patient are suggestive of bone marrow involvement. For definitive diagnosis, lymph node biopsy is sufficient.

The other aforementioned statements are ruled out because:
1. Renal impairment in NHL usually occurs as a consequence of ureteric obstruction secondary to intra-abdominal or pelvic lymph node enlargement.

2. Burkitt lymphoma is a high-grade NHL, which was first described in children in West Africa who presented with a jaw tumour, extra-nodal abdominal involvement, and ovarian tumours. It develops most often in children or young adults and is uncommon in older people.

3. High-grade lymphomas are potentially curable. They have a better prognosis and are responsive to chemotherapy unlike low-grade lymphomas, which are incurable with conventional therapy.

An MRI whole spine should be performed in a patient suspected of spinal metastasis which can occur before developing metastatic spinal cord compression. This patient has renal cell carcinoma, which readily metastasises to the bones and also has progressive back pain. He, therefore, needs urgent imaging of his spine before any neurological compromise develops. MRI whole spine is preferable because patients with spinal metastasis often have metastases at multiple levels within the spine. Plain radiographs and CT scans should not be performed as they have a lower sensitivity for revealing lesions and cannot exclude cord compression.

In general, imaging should be performed within one week if symptoms suspicious of spinal metastasis without neurological symptoms are present. If there are symptoms suggestive of malignant spinal cord compression, then imaging should be done within 24 hours.

The signs and symptoms of spinal metastases include:
1. Unrelenting lumbar back pain
2. Thoracic or cervical back pain
3. Pain associated with tenderness and worsens with sneezing, coughing, or straining
4. Nocturnal pain

The antithrombotic action of aspirin is due to inhibition of platelet function by acetylation of the platelet cyclooxygenase (COX) at the functionally important amino acid serine529. This prevents the access of the substrate (arachidonic aid) to the catalytic site of the enzyme at tyrosine385 and results in an irreversible inhibition of platelet-dependent thromboxane formation.

Poor prognostic factors for breast cancer include:
1. Young age (<40 years)
2. Premenopausal at the time of diagnosis
3. Increased tumour size
4. High-grade tumour
5. Oestrogen and progesterone receptor-negative tumour
6. Positive lymph node status

This patient has polycystic ovarian syndrome (PCOS). Medical management of PCOS is aimed at the treatment of metabolic derangements, anovulation, hirsutism, and menstrual irregularity.
First-line medical therapy usually consists of an oral contraceptive to induce regular menses. The contraceptive not only inhibits ovarian androgen production but also increases sex hormone-binding globulin (SHBG) production. The American College of Obstetricians and Gynaecologists (ACOG) recommends the use of combination low-dose hormonal contraceptive agents for long-term management of menstrual dysfunction.
If symptoms such as hirsutism are not sufficiently alleviated, an androgen-blocking agent may be added. Pregnancy should be excluded before therapy with oral contraceptives or androgen-blocking agents are started.
First-line treatment for ovulation induction when fertility is desired is clomiphene citrate. Second-line strategies may be equally effective in infertile women with clomiphene citrate–resistant PCOS.

A muscarinic receptor antagonist (MRA) is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. There are six antimuscarinic drugs currently marketed for the treatment of urge incontinence: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin.

IgA nephropathy’s characteristic presentation is haematuria following a non-specific upper respiratory infection as was evident in this case. IgA nephropathy also usually occurs in children and young males, like this patient.

After the exposure to chickenpox while pregnant, even if the patient is negative for antibodies she requires immunoglobulin to prevent further issues.

In myasthenia gravis, repeated muscle contractions lead to reduced muscle strength. The opposite is however classically seen in the related disorder Lambert-Eaton syndrome. Lambert-Eaton myasthenic syndrome is seen in association with small cell lung cancer, and to a lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune disorder. Lambert-Eaton myasthenic syndrome is caused by an antibody directed against pre-synaptic voltage gated calcium channel in the peripheral nervous system.

A Mongolian spot can be present in new born babies which usually appears over the back and fades with time. There is nothing to worry about.

Methotrexate lung disease (pneumonitis and fibrosis) is the specific etiological type of drug-induced lung disease. It can occur due to the administration of methotrexate which is an antimetabolite, which is given as disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxemia and tachypnoea are always present and crackles are frequently audible. Symptoms typically manifest within months of starting therapy. Methotrexate withdrawal is indicated in such cases.

Ankylosing spondylitis (spondylarthritis) is a chronic inflammatory disease of the axial skeleton that leads to partial or even complete fusion and rigidity of the spine. Males are disproportionately affected and upwards of 90% of patients are positive for the HLA-B27 genotype, which predisposes to the disease. The most characteristic early finding is pain and stiffness in the neck and lower back, caused by inflammation of the vertebral column and the sacroiliac joints. The pain typically improves with activity and is especially prominent at night. Other articular findings include tenderness to percussion and displacement of the sacroiliac joints (Mennell’s sign), as well as limited spine mobility, which can progress to restrictive pulmonary disease.
The most common extra-articular manifestation is acute, unilateral anterior uveitis. Diagnosis is primarily based on symptoms and x-ray of the sacroiliac joints, with HLA-B27 testing and MRI reserved for inconclusive cases. There is no curative treatment, but regular physiotherapy can slow progression of the disease. Additionally, NSAIDs and/or tumour necrosis factor-α inhibitors may improve symptoms. In severe cases, surgery may be considered to improve quality of life. The spine adopts a bamboo shape, not lordosis. The pain usually improves as the day progresses. leg raise test causes pain in cases of meningitis etc not in this case.

Primary amyloidosis is characterised by abnormal protein build-up in the tissues and organ such as the heart, liver, spleen, kidneys, skin, ligaments, and nerves. However, the most common cause of death in patients with primary amyloidosis is heart failure.

The CD15 antigen, also known as Lewis (hapten)X, serves as an immuno-phenotypic marker for Reed-Sternberg cells and its expression has diagnostic, but also prognostic significance in Hodgkin Lymphoma.

The key to this question is anti-smooth muscle antibodies. This is a finding of autoimmune hepatitis, which can be seen in type I diabetics. This also fits with her clinical picture. If you know these two facts, you should get every question correct regarding autoimmune hepatitis. Liver function testing is the best answer, then and should be elevated to indicate inflammation of the liver. Hepatic US, CK, thyroid function testing, short synacthen test are not helpful in the diagnosis of autoimmune hepatitis.

Beta-blockers are drugs of choice for patients with LQTS. The protective effect of beta-blockers is related to their adrenergic blockade, which diminishes the risk of cardiac arrhythmias. They may also reduce the QT interval in some patients.

Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

Subcutaneous low molecular weight heparin (LMWH) is the preferred treatment for most patients with acute DVT, including in pregnancy. A large meta-analyses comparing LMWH to unfractionated heparin (UFH) showed that LMWH decreased the risk of mortality, recurrent veno-thrombo embolism (VTE), and haemorrhage compared with heparin. Other advantages of LMWH may include more predictable therapeutic response, ease of administration and monitoring, and less heparin-induced thrombocytopenia. Disadvantages of LMWH include cost and longer half-life compared with heparin.

Warfarin, which is administered orally, is used if long-term anticoagulation is needed. The international normalized ratio (INR) is followed, with a target range of 2-3. Warfarin crosses the placenta and is teratogenic, causing a constellation of anomalies known as warfarin embryopathy, with greatest risk between the sixth and twelfth week of gestation.
Other options are not indicated for use.

Absolute risk reduction (ARR) – also called risk difference (RD) – is the most useful way of presenting research results to help your decision-making. Absolute risk reduction = (Control event rate) – (Experimental event rate) = 0.15 = 15%

Hepatitis C is a single-stranded positive sense RNA virus. It is variable because of the high rate of error of RNA-dependent RNA polymerase and the pressure from the host immune system has caused HCV to evolve and develop seven genetic lineages.

Heterochromia (difference in iris colour) is seen in congenital Horner’s syndrome, as well as anhidrosis. Other features of non-congenital Horner’s include miosis, ptosis and enophthalmos.

It is proven that spironolactone has survival benefits and loop diuretics only give symptomatic relief. Beta blockers are however, known to improve exercise tolerance, left ventricular function and reduce symptoms. They also reduce the mortality associated with heart failure. So administration of beta blockers will reduce the time spent in hospital by improving symptoms.

Carbon monoxide has high affinity for haemoglobin and myoglobin resulting in a left-shift of the oxygen dissociation curve and tissue hypoxia. There are approximately 50 deaths per year from accidental carbon monoxide poisoning in the UK. In these circumstances, antidotal therapy to block alcohol dehydrogenase with ethanol or 4-MP alone is insufficient to treat the poisoning. Data suggest that a severe lactic acidosis needs initial correction and in this patient the most appropriate treatment would be IV fluids with bicarbonate to correct the metabolic acidosis. Haemodialysis may be required thereafter.

The patient most likely suffers from Paget’s disease of the bone as his radiological examination shows both osteolytic and osteosclerotic lesions. Any bone or bones can be affected, but Paget’s disease occurs most frequently in the pelvis > lumbar spine > femur > thoracic spine > sacrum > skull > tibia.

Seasonal affective disorder (SAD) is a type of depression that’s related to changes in seasons. SAD begins and ends at about the same time every year. For most people with SAD, the symptoms start in the fall and continue into the winter months, sapping the person’s energy and making him feel moody. Less often, SAD causes depression in the spring or early summer.

Treatment for SAD may include light therapy (phototherapy), medications and psychotherapy.

Signs and symptoms of SAD may include:
Feeling depressed most of the day, nearly every day
Losing interest in activities you once enjoyed
Having low energy
Having problems with sleeping
Experiencing changes in your appetite or weight
Feeling sluggish or agitated
Having difficulty concentrating
Feeling hopeless, worthless or guilty
Having frequent thoughts of death or suicide.

Seasonal affective disorder is diagnosed more often in women than in men. And SAD occurs more frequently in younger adults than in older adults.

Factors that may increase your risk of seasonal affective disorder include:
Family history. People with SAD may be more likely to have blood relatives with SAD or another form of depression.
Having major depression or bipolar disorder. Symptoms of depression may worsen seasonally if you have one of these conditions.
Living far from the equator. SAD appears to be more common among people who live far north or south of the equator. This may be due to decreased sunlight during the winter and longer days during the summer months.