The main cardiovascular manifestations associated with Marfan’s syndrome are aortic dilatation and mitral valve prolapse.

The phrenic nerve provides the primary motor supply to the diaphragm, the major respiratory muscle.
Phrenic nerve paralysis is a rare cause of exertional dyspnoea that should be included in the differential diagnosis. Fluoroscopy is considered the most reliable way to document diaphragmatic paralysis. During fluoroscopy a patient is asked to sniff and there is a paradoxical rise of the paralysed hemidiaphragm. This is to confirm that the cause is due to paralysis rather than unilateral weakness.

Gamma delta T cells are of low abundance in the body, are found in the gut mucosa, skin, lungs and uterus, and are involved in the initiation and propagation of immune responses. Their ligands are not known in detail, but the gamma delta T cell receptors recognise intact proteins rather than MHC-presented peptides. Like alpha beta T cells, they develop in the thymus.

Mumps presents with a prodromal phase of general malaise and fever. On examination there is usually painful parotid swelling which has high chances of becoming bilateral. In OM with effusion there are no signs of infection and the only symptom is usually hearing loss. Acute otitis externa produces otalgia as well as ear discharge and itching. Acute OM produces otalgia and specific findings upon otoscopy. In acute mastoiditis the patient experiences ear discharge, otalgia, headache, hearing loss and other general signs of inflammation.

To differentiate VT from SVT with aberrant conduction the following electrocardiographic features should be looked for:

Evidence of preceding atrial activity for SVT. Oesophageal leads are helpful if P waves are hidden in the QRS complex.
QRS duration more than 140 ms for VT.
QRS morphology: Features of QRS morphology that favour SVT are RBBB or triphasic patterns like rSR in V1 and qRS in V6. Monophasic pattern like R or qR in V1 and rS or QS in V6 or multiple morphology QRS complexes favour VT.
AV dissociation for VT.

Brugada syndrome is an autosomal dominant disorder characterized by sudden cardiac death. The positive family history and characteristic ECG findings are in favour of Brugada syndrome. Usually the physical findings are normal.

Cryoglobulinemia may be caused by paraprotein bands such as those seen in Waldenström’s macroglobulinemia and multiple myeloma (MM). Meltzer’s triad of arthralgia, weakness, and palpable purpura are common to all types of cryoglobulinemia—as are membranoproliferative glomerulonephritis and low C4 levels. Raynaud’s phenomenon, however, occurs only in type 1 cryoglobulinemia, and its presence can be helpful in ascertaining the underlying cause.

Cryoglobulinemia is a condition in which the blood contains large amounts of pathological cold-sensitive antibodies called cryoglobulins—proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. One-third of the cases are idiopathic.

There are three types of cryoglobulinemia:
1. Type I (25%):
Monoclonal—IgG or IgM
Associated with multiple myeloma (MM), Waldenström’s macroglobulinemia

2. Type II (25%):
Mixed monoclonal and polyclonal—usually with rheumatoid factor (RF)
Associated with hepatitis C, rheumatoid arthritis (RA), Sjogren’s syndrome

3. Type III (50%):
Polyclonal—usually with RF
Associated with rheumatoid arthritis, Sjogren’s syndrome

Investigation results for cryoglobulinemia show low complement (especially C4) and high ESR. Treatment options include immunosuppression and plasmapheresis.

Acute dacryocystitis presents as inflammation of the lacrimal sac and is typically caused by infection. Symptoms of acute dacryocystitis can be pain, redness of the eye and swelling of the nasal aspect of the eye. The eye is usually watery and discharge can be expressed through the lacrimal punctum which is generally mucoid but can also be purulent. Patient can also present with fever.

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 most likely diagnosis with anaemia, raised erythrocyte sedimentation rate (ESR), hypercalcaemia, renal impairment, and raised total protein with low albumin is multiple myeloma (MM). Protein electrophoresis will confirm the presence of monoclonal band of paraprotein. Of note, a radioisotope bone scan is not a good test for picking up the lytic lesions of MM.

Diagnosis of MM is based on the confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria:
1. >30% plasma cells on bone marrow biopsy
2. Monoclonal band of paraprotein on electrophoresis: >35g/L for IgG, 20g/L for IgA, or >1g of light chains excreted in the urine per day

Minor criteria:
1. 10–30% plasma cells on bone marrow biopsy
2. Abnormal monoclonal band but levels less than listed above
3. Lytic bone lesions observed radiographically
4. Immunosuppression

Cefalexin should be avoided in this patient.
This patient is known to have a severe penicillin allergy. None of the above antibiotics are penicillin based. However, 0.5 – 6.5% of patients who are proven to have an IgE mediated penicillin allergy will also be allergic to cephalosporins, including cefalexin.

Penicillin, cephalosporins, and carbapenems are all members of the beta-lactam group of antibiotics and share a common beta-lactam ring. There is, therefore, a small risk of allergy cross-over between all these antibiotics. The rates of allergy cross-over are lower with second and third-generation cephalosporins than first-generation cephalosporins such as cefalexin.

It is important to question the patient carefully to ascertain what symptoms they had on exposure to penicillin. Symptoms such as an urticarial rash or itching make it more likely that they have an IgE mediated allergy.

Liver cirrhosis is not associated with hyposplenism.

Hyposplenism is caused by a variety of conditions. These are:
1. Splenectomy
2. Sickle cell anaemia
3. Coeliac disease, dermatitis herpetiformis
4. Graves’ disease
5. Systemic lupus erythematosus (SLE)

The rash is a characteristic sign of meningitis. Added to photophobia, headache and neck rigidity, meningitis is highly suggested diagnosis. IV antibiotics should be started immediately.

The most probable diagnosis in this patient is conversion disorder.

There may be underlying tension regarding her musical career which could be manifesting as apparent limb weakness.

Conversion disorder typically involves loss of motor or sensory function. The patient doesn’t consciously feign the symptoms (factitious disorder) or seek material gain (malingering). Patients may be indifferent to their apparent disorder – la belle indifference – although this has not been backed up by studies.

Other options:
Unexplained symptoms
There are a wide variety of psychiatric terms for patients who have symptoms for which no organic cause can be found:

Somatization disorder
Multiple physical symptoms present for at least 2 years
the patient refuses to accept reassurance or negative test results

Hypochondriacal disorder
The persistent belief in the presence of an underlying serious disease, e.g. cancer.
The patient again refuses to accept reassurance or negative test results

Dissociative disorder
Dissociation is a process of ‘separating off’ certain memories from normal consciousness
Unlike conversion disorder, it involves psychiatric symptoms e.g. amnesia, fugue, stupor
Dissociative identity disorder (DID) is the new term for multiple personality disorder as is the most severe form of dissociative disorder

Munchausen’s syndrome
Also known as factitious disorder
The intentional production of physical or psychological symptoms

Malingering
Fraudulent simulation or exaggeration of symptoms with the intention of financial or another gain.

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.

Generally, underlying causes of confusion need to be looked for and treated as appropriate, for example, hypercalcaemia, infection, urinary retention, and medication. If specific treatments fail, the following may be tried:

1. First choice: haloperidol
2. Other options: chlorpromazine, levomepromazine

In the terminal phase of the illness, agitation or restlessness is best treated with midazolam.

Varicella zoster virus (VZV) presents in this way and the rash transforms from macules to vesicles. Pneumonitis is a common complication of VZV infection.

Narrow complex tachycardia with hypotension is a medical emergency. Immediate synchronized cardioversion is the ideal management.

Zinc deficiency can present with alopecia, dermatitis, poor growth, increased susceptibility to infection, and cognitive deficiency. Magnesium deficiency can cause fatigue, cramping and an irregular EKG. Copper deficiency can present with fatigue and weakness. Chromium deficiency can present with hyperglycaemia.

In a patient with chronic alcoholism, one can expect confabulations, which point towards a diagnosis of Korsakoff’s syndrome.

Korsakoff’s is characterized by confabulation and amnesia, typically occurring in alcoholics secondary to chronic vitamin B1 (thiamine) deficiency.

Other options:
Dysthymia refers to mild depression.
Hydrophobia is a feature of rabies
Lilliputians may be observed in delirium tremens.
Perseveration is repetitive speech patterns, commonly seen after traumatic brain injury.

According to the Caine criteria, the presence of any two among the four following criteria can be used to clinically diagnose Wernicke’s Encephalopathy:
Dietary deficiency
Oculomotor abnormalities
Cerebellar dysfunction
Either altered mental status or mild memory impairment
Korsakoff psychosis:
Altered mental status – disorientation, confabulations
Oculomotor findings – most often horizontal nystagmus, ophthalmoplegia, cranial nerve IV palsy, conjugate gaze
Ataxia – wide-based gait

Treatment:
The mainstay of treatment in an acute presentation is thiamine replacement.
Electrolyte abnormalities should be corrected and fluids replaced.
In particular, magnesium requires replacement, as thiamine-dependent enzymes cannot operate in a magnesium-deficient state.
After the acute phase of vitamin and electrolyte replacement, memory rehabilitation is beneficial in Korsakoff syndrome.

Post-primary pulmonary tuberculosis is a chronic disease commonly caused by either endogenous reactivation of a latent infection or exogenous re-infection by Mycobacterium tuberculosis.
Post-primary pulmonary tuberculosis (also called reactivation tuberculosis) develops in 5%–20% of patients infected with M. tuberculosis.

Found mainly in adults, this form of tuberculosis arises from the reactivation of bacilli that lay dormant within a fibrotic area of the lung. In adults, reinfection with a strain of mycobacterium that differs from that which caused the primary infection is also possible. Predisposing factors include immunosuppression, diabetes, malnutrition and alcoholism.

Infliximab is a monoclonal antibody against tumour necrosis factor α (TNF-α). It is FDA approved for many autoimmune conditions, including rheumatoid arthritis and Crohn’s disease. One of the many known side effects of infliximab therapy is reactivation of latent tuberculosis (TB). Because of the resemblances in clinical and radiological features, tubercular lesions in the lung may mimic malignancy. TB accounts for 27% of all infections initially presumed to be lung cancer on imaging studies.

The patient has paroxysmal nocturnal haemoglobinuria (PNH) complicated by acute hepatic vein thrombosis (Budd–Chiari syndrome).

PNH is an acquired clonal disorder of haematopoietic stem cells, characterised by variable combination of intravascular haemolysis, thrombosis, and bone marrow failure. Diagnosis is made by flow cytometric evaluation of blood, which confirms the CD55 and CD59 deficiencies and deficiency of expression of other GPI-linked proteins. This test is replacing older complement-based assays such as the Ham test and sucrose lysis test.

Androgen deprivation therapy (ADT) for prostate cancer:

Goserelin (Zoladex) is a synthetic gonadotropin-releasing hormone (GnRH) analogue; chronic stimulation of goserelin results in suppression of LH, FSH serum levels thereby preventing a rise in testosterone.

Dosage form: 3.6 mg/10.8mg implants.

Adverse effects include flushing, sweating, diarrhoea, erectile dysfunction, less commonly, rash, depression, hypersensitivity, etc.

The patient is most likely suffering from Waldenström’s macroglobulinemia in which IgM paraproteinemia is found. Hyperviscosity syndrome can occur in the patients accounting for 10–15% of the cases.

Waldenström’s macroglobulinemia (also called lymphoplasmacytic lymphoma) is an uncommon type of non-Hodgkin lymphoma seen in older people. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein. Its features include monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; weight loss and lethargy; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

Sitagliptin-induced pancreatitis can occur at any time after the initiation of therapy, even after several years. Patients taking sitagliptin who present with signs and symptoms of mild or severe pancreatitis should immediately discontinue sitagliptin and use an alternate medication regimen for control of type 2 diabetes.
In response to pancreatitis reported in post-marketing surveillance through the Adverse Event Reporting System (AERS), the FDA has issued revised prescribing information for sitagliptin stating that cases of acute pancreatitis have been reported with use, to monitor closely for signs and symptoms of pancreatitis, and to use sitagliptin with caution in patients with a history of pancreatitis.

The direct Coombs test will specifically confirm immune-mediated haemolysis occurring post-transfusion in the aforementioned case.

There are two types of Coombs test used in immunohematology and immunology:

1. Direct Coombs test—It confirms autoimmune haemolytic anaemia by detecting antibodies or complement proteins attached to the surface of red blood cells.

2. Indirect Coombs test—It is used in prenatal testing of pregnant women and in testing prior to a blood transfusion. It detects antibodies floating freely in the blood, against foreign red blood cells.

Diabetic dermadromes constitute a group of cutaneous conditions commonly seen in people with diabetes with longstanding disease. Conditions included in this group are:
– Acral dry gangrene
– Carotenosis
– Diabetic dermopathy
– Diabetic bulla
– Diabetic cheiroarthropathy
– Malum perforans
– Necrobiosis lipoidica
– Limited joint mobility
– Scleroderma
– Waxy skin is observed in roughly 50%.

Sweet’s syndrome is also known as acute febrile neutrophilic dermatosis has a strong association with acute myeloid leukaemia. It is not associated with diabetes mellitus.

This patient presentation is unlikely to be an L5 nerve root lesion given the results of the MRI scan. Therefore, the most likely diagnosis is a mononeuritis affecting the left common peroneal nerve. This would lead to sensory loss over the dorsum of the foot and anterolateral leg on the left.

Achondroplasia is a common cause of dwarfism. It is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3). In normal development FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. The effect is genetically dominant, with one mutant copy of the FGFR3 gene being sufficient to cause achondroplasia, while two copies of the mutant gene are invariably fatal. A person with achondroplasia thus has a 50% chance of passing dwarfism to each of their offspring. People with achondroplasia can be born to parents that do not have the condition due to spontaneous mutation. It occurs as a sporadic mutation in approximately 80% of cases (associated with advanced paternal age) or it may be inherited as an autosomal dominant genetic disorder.
People with achondroplasia have short stature, with an average adult height of 131 centimeters (52 inches) for males and 123 centimeters (48 inches) for females.