Multiple Myeloma

Today we discussed a classic case of Multiple Myeloma with hypercalcemia, renal failure, anemia, and bone pain secondary to lytic bone lesions... these features make up the mnemonic CRAB: hyperCalcemia, Renal failure, Anemia, Bone pain.

Here is a link to a previous Horses & Zebras blog summarizing the Clinical Features of Multiple Myeloma, as well as some links to articles reviewing investigation and management of hypercalcemia and current management options for multiple myeloma.

Management of hypercalcemia +/- acute renal failure is often the primary problem that needs to be managed on admission to hospital. Hypercalcemia can be considered to be mild (2.6 - 2.9 mmol/L), moderate (3.0 - 3.4 mmol/L), and severe (greater than 3.5 mmol/L); however, there are no official cut-off points for hypercalcemia. As we discussed this morning, ~40% of calcium is bound to albumin and thus low albumin states will lower the measured calcium. This can be corrected roughly by adding 0.2 mmol/L to a calcium measurement for every drop in albumin of ~10.

Treatment of Hypercalcemia

1. First line treatment for hypercalcemia is fluid resuscitation, as the majority of patients will be volume contracted. Rapid, aggressive resuscitation is the goal, monitoring for any potential volume overload/heart failure in susceptible patients.

2. Administration of an IV bisphosphonate is also considered appropriate in severe hypercalcemia. Pamidronate (60 - 90 mg) is the usual choice, given once over 2-4 hours, and most often normalizing calcium within 5-7 days.

3. For more immediate calcium-lowering calcitonin can be considered; however, it is not uncommon for patients to develop tachyphylaxis and thus its use is limited.

4. Alternatively, and often more effective in the setting of lymphoma or multiple myeloma induced hypercalcemia, glucocorticoids such as prednisone (1 mg/kg daily) can be considered.

5. Management of hypercalcemia always includes investigation into the underlying cause, and treatment of such problem otherwise the hypercalcemia will recur.

Guillain-Barre Syndrome

This week we explored 2 different (potential) cases of Guillain-Barre Syndrome, or GBS. First during Physical Examination Rounds and then again in Morning Report.

The most common form of GBS is an idiopathic acute inflammatory demyelinating polyneuropathy (AIDP), and in fact GBS is often synonymous for AIDP. It is an autoimmune process directed against Schwann cell membranes. There are 5 other variants of GBS, including the Miller Fisher Variant which often presents with the triad of ophthalmoplegia, ataxia, and areflexia.

GBS occurs anywhere from 1 - 2 per 100,000 per year. It is often (~2/3 of cases) preceded by either a respiratory or GI infection, most commonly Campylobacter. GBS has also been reported after vaccinations and to be associated with systemic illnesses, such as SLE, Hodgkin's Lymphoma, Sarcoidosis, etc.

Patients with GBS often present with parasthesias in their limbs, followed soon after by ascending weakness. This progresses over days to weeks. GBS can also be associated with autonomic dsyfunction such as orthostasis, urinary retention, constipation, and tachycardia.

Physical examination most often reveals symmetrical motor weakness in an ascending pattern, with absent reflexes, flaccid tone, and a normal sensory exam.

Patients with GBS need to be monitored closely for respiratory failure due to involvement of the diaphragm. A good rule of thumb for consideration of intubation is the 20/30/40 rule:

• 20: Vital Capacity less than 20 cc/kg
  
• 30: Maximum Inspiratory Pressure less than 30 cm H2O
  
• 40: Maximum Expiratory Pressure less than 40 cm H2O

Treatment for GBS is most often supportive, and may require an ICU setting for ventilatory support, hemodynamic support, nutritional support, and pain control. If diagnosed within the first 4 weeks then IVIG or plasmapheresis can be considered. A recent Cochrane review suggests that IVIG treatment has similar outcomes to plasmapheresis in the setting of early (ie: within 2 weeks) diagnosed GBS.

Outcomes for patients with GBS are quite good with ~80% achieving full recovery within a few months to a year; however, minor deficits often persist. 5-10% will have permament disabling deficits, and another 2-3% will die as a result of their GBS. Approximately 5-10% of patients may develop one or more relapses of their GBS, leading to a diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy (CIPD).

Here is a very thorough review of GBS from 2005, in The Lancet.

Pulmonary Hypertension

Today we discussed a case of newly diagnosed Pulmonary Hypertension in a young woman.

Pulmonary Hypertension (PH) is defined as a Pulmonary Arterial Pressure over 25 mmHg at rest (normal 12-16 mmHg).

Patients often present with months or years of gradually progressive symptoms, such as shortness of breath, fatigue, cough, angina, peripheral edema, and rarely hemoptysis.

Cardiovascular examination often reveals a loud, palpable P2, a split S2, and an RV heave.

There are multiple causes of PH, but all result in increased pressures within the pulmonary vasculature, either due to vasoconstriction of the blood vessels, obstruction by way of a mass or pulmonary emboli, or fibrosis within the lung parenchyma related to systemic illnesses. In order to overcome this increased pulmonary pressure, the heart then is required to create elevated right-sided pressures in the heart. In turn, this leads to RV hypertrophy and potentially RV failure.

PH is classified according to the WHO into 5 major categories:
Class I: Pulmonary Arterial Hypertension

Idiopathic

Familial

Connective Tissue Disorders, HIV, Drugs, Toxins, Congenital Left-to-Right Shunts, etc.
Class II: PH with Left Heart Disease

Left Atrial or Ventricular Heart Disease

Left-sided Valvular Heart Disease
Class III: PH Associated with Lung Diseases or Chronic Hypoxia

COPD, Interstitial Lung Disease, Sleep Disordered Breathing, etc.
Class IV: PH Due to Chronic Thrombotic and/or Embolic Disease

Thromboembolic obstruction of the proximal or distal pulmonary arteries

Nonthrombotic obstruction of the pulmonary arteries (ie: tumor, foreign body, etc.)
Class V: Miscellaneous causes

Sarcoidosis, Lymphangiomatosis, etc.

Given the numerous potential causes for PH, any patient with suspected PH requires significant investigations to diagnose PH and then to determine the etiology of their PH. This includes basic blood work (looking for evidence of polycythemia), an ECG (evidence of RAE or RVH), a CXR, and echocardiogram, a CT Chest, a V/Q scan (to detect chronic thromboembolic disease), a 6-minute walk test, and a Right-Heart Catheterization to name a few!

These patients are managed by the multidisciplinary PH team where the goals of treatment include symptom management, improving quality of life, and prolonging survival, which often requires a lung or heart-lung transplant.

Here is a review article on the mechanisms of PH, and here are the 2009 American College of Cardiology Consensus Guidelines for PH.