Alkaptonuria

- rare (1:200,000) disorder of tyrosine metabolism
- autosomal recessive
- deficiency of homogentisic acid oxidase
- leads to excretion of large amount of homogentisic acid in urine and accumulation of oxidised homogentisic acid pigment in connective tissues (ochronosis)
- presents with dark urine, foci of gray-brown scleral pigment, darkening of concha, anthelic and helix of ear
- ochronotic arthritis is heralded by pain, stiffness and some limitation of motion of hips, knees and shoulders
- interverterbral disc calcification is characteristic of alkaptonuria and is seen on spinal X rays
- degenerative cardiovascular disease is increased in older patients
- treatment: Nitisinone

Multiple myeloma

- represents a malignant proliferation of plasma cells derived from a single clone
- incidence increases with age, median age at diagnosis is 70 years
- males are more commonly affected than females
- classic triad of myeloma is marrow plasmacytosis (>10%), lytic bone lesions and serum and/or urine M component

Clinical manifestations
- bone pain is the most common symptom in myeloma (70%), which usually involves the back and ribs. The pain of myeloma is precipitated by movement, unlike pain of metastatic carcinoma which usually worse at night. Osteoclastic activity is mediated by osteoclast activating factors made by myeloma cells
- susceptibility to bacterial infections (usually pneumonias and pyelonephritis) caused by hypogammaglobulinaemia. 
- renal failure (most commonly caused by hypercalcemia. Other causes are glomerular deposits of amyloid, hyperuricemia, tubular damage by light chains, frequent use of NSAIDs, infiltration of kidney by myeloma cells, use of iodinated contrast dye for imaging). Earliest manifestation of tubular damage is adult Fanconi syndrome
- normochromic normocytic anaemia caused by replacement of normal marrow by expanding tumor cells, inhibition of hematopoiesis by factors made by tumor and reduced production of erythropoeitin by kidney
- hyperviscosity may developed depending on physical properties of M component (most common with IgM, IgG3 and IgA paraprotein)

Diagnosis
- important differential diagnosis are MGUS (serum M protein <30g/L and bone marrow clonal plasma cells <10%) and asymptomatic/smoldering myeloma
- Investigations
i) Chest and bone radiographs - lytic lesions or diffuse osteopenia
ii) Full blood picture- anemia and Rouleux formation
iii) ESR - elevated
iv) serum calcium, urea nitrogen, creatinine and uric acid levels may be elevated
v) serum and urine protein electrophoresis - characteristic M spikes
vi) 24-h urine specimen to quantiate Bence Jones protein excretion
vii) serum B2-microglobulin (single most powerful predictor of survival)






Treatment
- 10% of patients with indolent/smoldering myeloma only require antitumor therapy when the disease becomes symptomatic
- supportive care directed at the anticipated complications (bisphosphonates, steroid, hydration for hypercalcemia; plasmapheresis for acute renal failure and hyperviscosity syndrome)
- Bortezomib (proteasome inhibitor) and lenalidomide combined with dexamethasone obtained high response rate (>80%) without compromising stem cell collection for transplantation
- For patients not transplant candidate, therapy consisting of intermittent pulses of an alkylating agent, melphalan with prednisolone
- radiotherapy is effective for bony lesions
- Median survival is 7-8 years. Major causes of death are progressive myeloma, renal failure, sepsis, or therapy-related myelodysplasia

Henoch-Schonlein Purpura

- a.k.a anaphylactoid purpura
- small vessel vasculitis characterised by palpable purpura (usually over buttocks and lower extremities), arthralgia, gastrointestinal signs and symptoms and glomerulonephritis
- presumptive pathogenic mechanism for HSP is immune complex deposition (usually IgA)
- palpable purpura is seen in virtually all paediatric patients
- gastrointestinal involvement is characterised by colicky abdominal pain associated with nausea, vomiting, diarrhea or constipation frequently accompanied by passage of blood and mucus per rectum, bowel intussusception may occur
- diagnosis of HSP is based on clinical signs and symptoms
- skin biopsy : leukocytoclastic vasculitis
- excellent prognosis, 1-5% of children progress to ESRF
- treatment: prednisolone (1mg/kg) has been shown to be useful in decreasing tissue edema, arthralgia and abdominal discomfort
- patients with rapidly progressive glomerulonephritis have been anecdotally reported to be benefit from intensive plasma exchange combined with cytotoxic drugs

Pneumothorax

Pneumothorax is the presence of gas in pleural space

Primary spontaneous pneumothorax
- occurs without antecedent trauma to thorax and in the absence of underlyign lung disease, usually due to rupture of apical pleural blebs.
- occurs almost exclusively in smokers (lifetime risk of 12% in smoker as compared to 0.1% in non smoker)
- initial recommended treatment : simple aspiration
- supplementary high flow oxygen should be given to reduce the total pressure of gases in pleural capillaries by reducing the partial pressure of nitrogen, thus increase the pressure gradient between pleural capillaries and pleural cavity thereby increasing absorption of air from pleural cavity
- strong emphasis should be placed on the relationship between the recurrence of pneumothorax and smoking in an effort to encourage patient to stop smoking (recurrence rate of 54% within first 4 years)



Secondary pneumothorax
- due to chronic obstructive pulmonary disease
- clinical symptoms associated with secondary pneumothoraces are more severe than those associated with primary spontaneous pneumothoraces (lack of pulmonary reserve)



Traumatic pneumothorax
- penetrating or non-penetrating chest trauma
- should be treated with tube thoracostomy unless they are very small

Tension pneumothorax
- positive pleural pressure is life threatening because ventilation is severely compromised and positive pressure is transmitted to mediastinum, resulting in decreased venous return to the heart and reduced cardiac output
- large bore needle should be inserted into pleural space through the second anterior intercostal space

Size of pneumothorax depending on the visible rim between lung margin and chest wall
- small < 2cm (less than 50% of hemithorax)
- large ≥ 2cm (more than 50%)



Pneumothoraces which failed to respond within 48 hours should be referred to a respiratory physician. In case of persistent air leak or failure of lung to re-expand, the managing respiratory specialist should seek and early (3-5days) thoracic surgical opinion

Patients discharged without intervention should avoid air travel until a chest radiograph confirmed the resolution of pneumothorax. Diving should be permanently avoided after pneumothorax unless patient had bilateral surgical pleurectomy

Source: BTS guidelines for the management of spontaneous pneumothorax
             18th edition Harrison's principle of internal medicine