Squamous-cell carcinoma is the most common histological type of lung cancer to cavitate (82% of cavitary primary lung cancer), followed by adenocarcinoma and large cell carcinoma. Multiple cavitary lesions in primary lung cancer are rare, however, multifocal bronchoalveolar cell carcinoma can occasionally have multiple cavitary lesions. Small cell carcinoma is not known to cavitate.

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.

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 patients high morning blood sugar levels are suggestive to Somogyi Phenomenon which suggests that hypoglycaemia during the late evening induced by insulin could cause a counter regulatory hormone response that produces hyperglycaemia in the early morning.
Substitution of regular insulin with an immediate-acting insulin analogue, such as Humulin lispro, may be of some help.

The peak incidence of seizures is expected 36 hours following the onset of alcohol withdrawal.

Pathophysiology:
Chronic alcohol consumption enhances GABA mediated inhibition in the CNS (similar to benzodiazepines) and inhibits NMDA-type glutamate receptors. Alcohol withdrawal is thought to lead to the opposite (decreased inhibitory GABA and increased NMDA glutamate transmission).

Clinical course in alcohol withdrawal:
Symptoms begin 6-12 hours following the onset of alcohol withdrawal
Seizures occur 36 hours following the onset of withdrawal
Delirium tremens (coarse tremor, confusion, delusions, auditory and visual hallucinations, fever, tachycardia) occurs approximately 72 hours after the onset of alcohol withdrawal.

Management
First-line: benzodiazepines e.g. lorazepam, chlordiazepoxide.
Carbamazepine is also effective in the treatment of alcohol withdrawal.
Phenytoin is said not to be as effective in the treatment of alcohol withdrawal seizures.

Reactive arthritis, (formerly known as Reiter’s syndrome), is an autoimmune condition that occurs after a bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondylarthritis because of its association with HLA-B27. Reactive arthritis primarily affects young men and usually presents with musculoskeletal or extra‑articular symptoms. The characteristic triad consists of arthritis, conjunctivitis, and urethritis. Symmetric lower limb arthropathy and a sterile joint aspirate points towards reactive arthropathy.

Bronchiectasis is a long-term condition where the airways of the lungs become abnormally widened, leading to a build-up of excess mucus that can make the lungs more vulnerable to infection. The most common symptoms of bronchiectasis include:
– a persistent productive cough
– breathlessness.

The 3 most common causes in the UK are:
– a lung infection in the past, such as pneumonia or whooping cough, that damages the bronchi
– underlying problems with the immune system (the body’s defence against infection) that make the bronchi more vulnerable to damage from an infection
– allergic bronchopulmonary aspergillosis (ABPA) – an allergy to a certain type of fungi that can cause the bronchi to become inflamed if spores from the fungi are inhaled

The clinical picture points to Lambert– Eaton myasthenic syndrome (LEMS) which often presents with weakness of the arms and legs. In LEMS, antibodies against voltage-gated calcium channels (VGCC) decrease the amount of calcium that can enter the nerve ending, causing autonomic symptoms like dry mouth and slurring of speech, as seen in this patient.

Bilateral occipital cortex infarction will produce varying degrees of cortical blindness, wherein the patient has no vision but fundoscopy findings are normal. When there are extensive lesions, patients my present with denial of their condition, known as Anton’s Syndrome, and begin to describe objects that they have never seen before.

This man has a small-cell lung cancer (SCLC) and associated Lambert-Eaton myasthenic syndrome – a well-recognized paraneoplastic manifestation of SCLC. This classically affects the proximal muscles, especially in the legs, causing difficulty in standing from a seated position and climbing stairs. In contrast to myasthenia gravis, eye involvement is uncommon. Treatment with steroids is often helpful, which explains his transient symptomatic improvement during treatment for his COPD exacerbation. Steroid myopathy does not fit as the symptoms started well before his course of prednisolone. Although the patient is mildly hypercalcaemic, this would not be sufficient to produce his presenting symptoms, although it does reinforce the suspicion of lung malignancy. Motor neurone disease would be unlikely in this context and would not improve with steroids. Myasthenia gravis could produce these symptoms, but in the context of a new lung mass is a less viable diagnosis.

Primary hyperparathyroidism (PHPT) is diagnosed based upon levels of blood calcium and parathyroid hormone (PTH). In most people with PHPT, both levels are higher than normal. Occasionally, a person may have an elevated calcium level and a normal or minimally elevated PTH level. Since PTH should normally be low when calcium is elevated, a minimally elevated PTH is considered abnormal and indicates PHPT.

A typical attack may last less than an hour but can also persist for longer. In primary Raynaud’s, attacks are more likely symmetric, episodic, and without evidence of peripheral vascular disease. Patients more commonly have a negative ANA and normal inflammatory markers. There should be no evidence of tissue gangrene, digital pitting, or tissue injury in primary Raynaud’s. In contrast, patients with secondary Raynaud’s will describe attacks that are more frequent, painful, often asymmetric and may lead to digital ulcerations.

West Nile virus (WNV) is a single-stranded RNA flavivirus transmitted via the culex mosquito. This previously ‘tropical’ disease has became topical in recent years following a large scale outbreak in the New York area. Incidence of neurological involvement is around 1%, although some suggest that the incidence of meningoencephalitis in America is higher than in other parts of the world. Risk factors for neurological involvement include increasing age, and immunosuppression. The usual picture is of sudden onset fever and myalgia with nausea and vomiting and a non-specific rash. Transient meningitis is occasionally seen. Frank meningoencephalitis is seen in two-thirds of cases with neurological involvement; 15% progress to coma. A flaccid paralysis similar to acute Guillain–Barré is increasingly recognised.
Diagnosis is initially clinical with subsequent serological confirmation. Treatment is supportive; results from trials of antivirals have yielded disappointing results.

Carbon monoxide (CO) poisoning, considered as the great imitator of other diseases, as the patients present with a myriad of symptoms. The carbon monoxide diffuses rapidly across the pulmonary capillary membrane binding to the haem molecule with a very high affinity (240 times that of oxygen) forming carboxy-haemoglobin (COHb). Non-smokers have a baseline COHb of ,3% while smokers have a baseline COHb of 10-15%.

Use of Hyperbaric oxygen therapy (HBOT) for treatment of mild to moderate CO poisoning is not routine.
The selection criteria for HBOT in cases of CO poisoning include:
• COHb levels > 20-25%
• COHb levels > 20% in pregnant patient
• Loss of consciousness
• Severe metabolic acidosis (pH <7.1)
• Evidence of end-organ ischemia (e.g., ECG changes, chest pain, or altered mental status)
Principle of HBOT:
Exposing patients to 100 percent oxygen under supra-atmospheric conditions results in a decrease in the half-life (t1/2) of COHb, from , 90 min in atmospheric air to , 30 minutes. The amount of oxygen dissolved in the blood also rises from , 0.3 to 6 mL/dL, increasing the delivery of non-haemoglobin-bound oxygen to the tissues.

Post-traumatic stress disorder (PTSD) is an anxiety disorder caused by stressful, frightening or distressing events.

PTSD is a lasting consequence of traumatic ordeals that cause intense fear, helplessness, or horror, such as a sexual or physical assault, the unexpected death of a loved one, an accident, war, or natural disaster. Families of victims can also develop PTSD, as can emergency personnel and rescue workers.

PTSD is diagnosed after a person experiences symptoms for at least one month following a traumatic event. However symptoms may not appear until several months or even years later. The disorder is characterized by three main types of symptoms:
-Re-experiencing the trauma through intrusive distressing recollections of the event, flashbacks, and nightmares.
-Emotional numbness and avoidance of places, people, and activities that are reminders of the trauma.
-Increased arousal such as difficulty sleeping and concentrating, feeling jumpy, and being easily irritated and angered.

The goal of PTSD treatment is to reduce the emotional and physical symptoms, to improve daily functioning, and to help the person better cope with the event that triggered the disorder. Treatment for PTSD may involve psychotherapy (a type of counselling), medication, or both.

Eye Movement Desensitization and Reprocessing (EMDR) therapy was initially developed in 1987 for the treatment of posttraumatic stress disorder (PTSD) and is guided by the Adaptive Information Processing model. EMDR is an individual therapy typically delivered one to two times per week for a total of 6-12 sessions, although some people benefit from fewer sessions. Sessions can be conducted on consecutive days.

Drug treatments (paroxetine, mirtazapine, amitriptyline or phenelzine) should be considered for the treatment of PTSD when a sufferer expresses a preference to not engage in trauma-focused psychological treatment.

Hyperthyroid patients show significantly lower resting arterial CO2 tension, tidal volume and significantly higher mean inspiratory flow and pa(O2) than healthy patients. This may of course lead to misdiagnosis of patients with hyperthyroidism as having hyperventilation syndrome.

CADASIL is the most common form of hereditary stroke disorder. This case has a strong history of migraine with aura with stroke-like episodes, characteristic of CADASIL. Additionally, there is positive family history of migraine and early dementia but no other vascular risk factors like hypertension, diabetes, or hypercholesterolaemia, which all confirm the suspicion of CADASIL, an arteriopathy where there is thickening of the smooth muscle cells in the blood vessels.

Insulin is produced by the beta-cells in the islets of Langerhans in the pancreas while Glucagon is secreted from the alpha cells of the pancreatic islets of Langerhans.
Type 1 diabetes mellitus is the culmination of lymphocytic infiltration and destruction of the beta cells of the islets of Langerhans in the pancreas. As beta-cell mass declines, insulin secretion decreases until the available insulin is no longer adequate to maintain normal blood glucose levels. After 80-90% of the beta cells are destroyed, hyperglycaemia develops and diabetes may be diagnosed.

The clinical manifestations of Small cell lung cancer (SCLC) can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
Hypertrophic pulmonary osteoarthropathy (HPO) is a rare paraneoplastic syndrome that is frequently associated with lung cancer; however, the incidence of clinically apparent HPO is not well known.
SIADH is present in 15% of cases and most commonly seen.
Although hypercalcaemia is frequently associated with malignancy, it is very rare in small cell lung cancer despite the high incidence of lytic bone metastases.
Ectopic Cushing’s syndrome in SCLC does not usually exhibit the classic signs of Cushing’s syndrome and Cushing’s syndrome could also appear during effective chemotherapy.
Chemotherapy is the treatment of choice in SCLC.

The water deprivation test (i.e., the Miller-Moses test), is a semiquantitative test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis. It is typically performed in patients with more chronic forms of Diabetes Insipidus (DI). The extent of deprivation is usually limited by the patient’s thirst or by any significant drop in blood pressure or related clinical manifestation of dehydration.

In healthy individuals, water deprivation leads to a urinary osmolality that is 2-4 times greater than plasma osmolality. Additionally, in normal, healthy subjects, administration of ADH produces an increase of less than 9% in urinary osmolality. The time required to achieve maximal urinary concentration ranges from 4-18 hours.

In central and nephrogenic DI, urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI. In primary polydipsia, urinary osmolality will be above 750 mOsm/kg after water deprivation.
A urinary osmolality that is 300-750 mOsm/kg after water deprivation and remains below 750 mOsm/kg after administration of ADH may be seen in partial central DI, partial nephrogenic DI, and primary polydipsia.

Diagnosis of RA is mainly based on clinical features (e.g., morning stiffness, symmetrical joint swelling) and laboratory tests (e.g., anti-CCP). Rheumatoid factor is not very specific for this disease and hence has low reliability. X-ray findings (e.g., soft tissue swelling or joint space narrowing) occur late in the disease and are therefore not typically used for diagnosis.

Cabergoline, an ergot derivative, is a long-acting dopamine agonist. It is usually better tolerated than Bromocriptine (BEC), and its efficacy profiles are somewhat superior to those of BEC. It offers the convenience of twice-a-week administration, with a usual starting dose of 0.25 mg biweekly to a maximum dose of 1 mg biweekly. Some studies have shown efficacy even with once-a-week dosing. Cabergoline appears to be more effective in lowering prolactin levels and restoring ovulation. Up to 70% of patients who do not respond to BEC respond to cabergoline.

Malignant mesothelioma is a type of cancer that occurs in the thin layer of tissue that covers the majority of the internal organs (mesothelium).
Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumour of the pleura and peritoneum. Aetiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen.

Thoracoscopically guided biopsy should be performed if mesothelioma is suggested; the results are diagnostic in 98% of cases. No specific treatment has been found to be of benefit, except radiotherapy, which reduces seeding and invasion through percutaneous biopsy sites.

Median survival for patients with malignant mesothelioma is 11 months. It is almost always fatal.

Alpha1-antitrypsin (AAT) deficiency, first described in 1963, is one of the most common inherited disorders amongst white Caucasians. Its primary manifestation is early-onset of pan acinar emphysema. In adults, alpha1-antitrypsin deficiency leads to chronic liver disease in the fifth decade. As a cause of emphysema, it is seen in non-smokers in the fifth decade of life and during the fourth decade of life in smokers.

Symptoms of alpha1-antitrypsin (AAT) deficiency emphysema are limited to the respiratory system. Dyspnoea is the symptom that eventually dominates alpha1-antitrypsin deficiency. Similar to other forms of emphysema, the dyspnoea of alpha1-antitrypsin deficiency is initially evident only with strenuous exertion. Over several years, it eventually limits even mild activities.
The serum levels of some of the common genotypes are:
•PiMM: 100% (normal)
•PiMS: 80% of normal serum level of A1AT
•PiSS: 60% of normal serum level of A1AT
•PiMZ: 60% of normal serum level of A1AT, mild deficiency
•PiSZ: 40% of normal serum level of A1AT, moderate deficiency
•PiZZ: 10–15% (severe alpha 1-antitrypsin deficiency)

Depressive disorders require long-term treatment with antidepressants, psychotherapy, or both. The goal of antidepressant therapy is complete remission of symptoms and return to normal daily functioning. Studies have shown that achieving remission and continuing antidepressant therapy long after the acute symptoms remit can protect against the relapse or recurrence of the psychiatric episode. Many patients, however, inadvertently or intentionally skip doses of their antidepressant, and even discontinue it, if their symptoms improve or if they experience side effects. Antidepressant discontinuation may increase the risk of relapse or precipitate certain distressing symptoms such as gastrointestinal complaints, dizziness, flu-like symptoms, equilibrium disturbances, and sleep disorders.

Pharmacologic therapy should be continued long enough to sustain remission and avoid relapses and recurrences. Recurrence refers to a return of depression at a time beyond the expected duration of the index episode (> 9 months after remission). This means that physicians and patients alike should not be too eager to discontinue medication prematurely. An interval of 6 months has been thought to be the usual duration of antidepressant therapy. New recommendations, however, suggest that treatment should continue for up to 9 months after symptoms have resolved (continuation phase) to prevent relapse and for longer to help prevent recurrence (maintenance phase).

SSRI discontinuation symptoms are similar to those of the TCAs, with dizziness, gastrointestinal symptoms, and sleep disorders common. Anecdotal reports have included complaints of “electric shock–like” sensations, flashes, and “withdrawal buzz.” The type and severity of the symptoms correlate with the relative affinities of the agents for the serotonin reuptake sites and with secondary effects on other neurotransmitters; with SRIs that also affect cholinergic systems, the symptoms possibly correlate with cholinergic rebound.

Blood pressure should be routinely measured as leflunomide may cause hypertension and thus an increase in BP. It doesn’t cause changes in blood sugar levels, peak expiratory flow rate or haematuria.

The most probable diagnosis in this patient is post-traumatic stress disorder (PTSD). The first-line treatment for this patient would be cognitive behavioural therapy or eye movement desensitization and reprocessing therapy.

Post-traumatic stress disorder (PTSD) can develop in people of any age following a traumatic event, for example, a major disaster or childhood sexual abuse. It encompasses what became known as ‘shell shock’ following the first world war. One of the DSM-IV diagnostic criteria is that symptoms have been present for more than one month.

Clinical features:
Re-experiencing: flashbacks, nightmares, repetitive and distressing intrusive images
Avoidance: avoiding people, situations or circumstances resembling or associated with the event
Hyperarousal: hypervigilance for threat, exaggerated startle response, sleep problems, irritability and difficulty concentrating
Emotional numbing – lack of ability to experience feelings, feeling detached from other people
Depression
Drug or alcohol misuse
Anger

Management:
Following a traumatic event single-session interventions (often referred to as debriefing) are not recommended
Watchful waiting may be used for mild symptoms lasting less than 4 weeks
Trauma-focused cognitive-behavioural therapy (CBT) or eye movement desensitization and reprocessing (EMDR) therapy may be used in more severe cases
Drug treatments for PTSD should not be used as a routine first-line treatment for adults.
If drug treatment is used then paroxetine or mirtazapine are recommended.

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.

Chronic obstructive pulmonary disease (COPD) is a complex and progressive chronic lung disease. Typically, COPD includes emphysema and chronic bronchitis. COPD is characterized by the restriction of airflow into and out of the lungs. The obstruction of airflow makes breathing difficult. The causes of COPD include smoking, long-term exposure to air pollutants and a rare genetic disorder.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) developed the GOLD Staging System. In the GOLD System, the forced expiratory volume in one second (FEV1) measurement from a pulmonary function test is used to place COPD into stages. Often, doctors also consider your COPD symptoms.

COPD has four stages. The stages of COPD range from mild to very severe. COPD affects everyone differently. Because COPD is a progressive lung disease, it will worsen over time.
The Stages of COPD:
Mild COPD or Stage 1—Mild COPD with a FEV1 about 80 percent or more of normal.
Moderate COPD or Stage 2—Moderate COPD with a FEV1 between 50 and 80 percent of normal.
Severe COPD or Stage 3—Severe emphysema with a FEV1 between 30 and 50 percent of normal.
Very Severe COPD or Stage 4—Very severe or End-Stage COPD with a lower FEV1 than Stage 3, or people with low blood oxygen levels and a Stage 3 FEV1.

This patient has a FEV1 percent of 63 which falls within the stage 2 or moderate COPD.

Osteoarthritis (OA) is a disabling joint disease characterized by a noninflammatory degeneration of the joint complex (articular cartilage, subchondral bone, and synovium) that occurs with old age or from overuse. It mainly affects the weight-bearing and high-use joints, such as the hip, knee, hands, and vertebrae. Despite the widespread view that OA is a condition caused exclusively by degenerative “wear and tear” of the joints, newer research indicates a significant heterogeneity of causation, including pre-existing peculiarities of joint anatomy, genetics, local inflammation, mechanical forces, and biochemical processes that are affected by proinflammatory mediators and proteases. Major risk factors include advanced age, obesity, previous injuries, and asymmetrically stressed joints. In early-stage osteoarthritis, patients may complain of reduced range of motion, joint-stiffness, and pain that is aggravated with heavy use. As the disease advances, nagging pain may also occur during the night or at rest. Diagnosis is predominantly based on clinical and radiological findings. Classic radiographic features of OA do not necessarily correlate with clinical symptoms and appearance. RA involves proximal interphalangeal joints not distal. Gout occurs as a result of overproduction or underexcretion of uric acid and frequently involves first toe. Fibromyalgia is a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues.