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MICA (P) 031/04/2010

Jan.Feb.Mar 2012

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1 4 CUSTOMISED KNEE REPLACEMENT? PATIENT-SPECIFIC INSTRUMENTATION CASES WE SAW IN THE CLINICS AND WARDS, PART 3 11 SUPPLEMENTATION IN NUTRITIONAL ANAEMIA 17 RADIOLOGY QUIZ 20 ECG QUIZ

Medical
Jan.Feb.Mar 2012

From The Editor


I need not remind to the reader that the world is changing. Changes to the practice of medicine have been profound and are ever gathering speed. I can quote some personal examples. In 1987, I had to accompany brain-injured patients in siren-blaring ambulances to TTSH in the middle of the night because that is where the only CT scanner in the country was. Now, even junior doctors can order CT or MRI scans in their own institutions. When I returned to the hospitals in 1990 after two years in military service, I was lost for a while because the conventional units (for instance, venous glucose was reported in mg/dl) gave way to the SI system (mmol/l). I never developed intuitive grasp of what a glucose level in mmol/l means. There has been a proliferation of gadgets for monitoring, moving, probing and treating patients. Index Medicus has yielded to PubMed. In the early years of my career, metal needles had to be sharpened after use and glass syringes re-packaged for sterilization. As befit our modern throw-away culture, all these and more are now single-use and disposable. Henning Mankell had his character Wallander lament that the Swedes do not value things and people anymore, since people stopped darning their socks and simply replaced them. The most profound changes are in the people who constitute the heath care system. Most people in charge do not exert regimental control over their charges anymore (some miss this). Most doctors now do not come from low-income families, so we cannot expect them to have built-in empathy for the poor. Younger people do not accord respect to older people merely because of their age or their titles, which is actually not a bad thing except to the older people. There is only one way to get respect: earn it! A large group of younger doctors are unable to obtain history from older Chinese patients. We perceive that more and more colleagues have a lets-see-what-I-can-get-away-with attitude rather than an ethical code. Bedside clinical skills are declining because of heavier reliance on tests and equipment in succeeding batches of doctors. Bob Dylan wrote: Theres a battle outside and it is ragin; Itll soon shake your windows and rattle your walls; For the times they are a-changin. I belong to the baby-boomer generation (people born between 1946 and 1964) that experienced these changes. I think we have to know which changes are good and which arent. We cannot hold it against our juniors that they do not know the past, because they were not there. We have to figure out new ways to interact with them. Putting aside our rose-tinted glasses, the past was not what we remember it to be. There was favouritism, maverick management and bullying, all of which are harder to perpetuate now. I doubt that people were more morally upright in the past. Those of us who are older should learn from the young and see what makes them click. They can help us dispense with our rigid ways of thinking. Those of us who are younger should see what values we have lost. And remember that in twenty years time, we will be saying the same things to the even younger folks.

digest

Dr Leong Khai Pang EDITOR Medical Digest

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Customised knee replacement?

Medical Progress

Patient-specific instrumentation

Improved prosthesis design and better material science over the last three decades have improved not only the function but also the longevity of contemporary knee replacement. However, even the most advanced and well designed knee implant needs to be implanted accurately so that it will function the way it is designed to. More importantly, the limbs mechanical axis must be restored accurately.

Classically, a surgeon depends on specially designed jigs to aid in the osteotomy and the placement of the implants. Combining X-ray templating and the surgeons experience, fairly consistent results have been achieved. However, there are still a significant number of patients who are outliers to the norm, in which the knee implant is not accurately implanted, often because the mechanical axis has not been accurately restored. C O M P U T E R N AV I G AT I O N A N D PAT I E N T - S P E C I F I C I N S T R U M E N TAT I O N Despite excellent results in knee replacement, we know from experience that if a prosthesis is not accurately implanted, early revision is often the consequence. Total knee arthroplasty in varus alignment fail because of medial tibial collapse while those in valgus alignment do so from ligamentous instability.1 The intramedullary design of jigs may also result in fat embolism and bleeding from the bone canal. Computer navigation was introduced about a decade ago to address some of these issues. The aim was to extend longevity and prolong function of a replaced knee, in tandem with improved implant design. Computer navigation also minimised the variability to produce a more consistent knee surgery outcome every time. However, computer-navigated surgery never became very popular as there is a fairly steep learning curve and they take longer time to perform. Economically there is also a capital

outlay for the purchase of expensive computer navigation system. Advances in medical imaging, computer modelling, and material

science have advanced to allow surgeons to more accurately implant a replaced knee. Patient-specific instrumentation (PSI) is such a recent development. An MRI image

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of a patients limb is rendered and segmented by a computer, then presented to a surgeon in threedimensional format on a computer screen. The surgeon then plans his surgery virtually, and obtains feedback of his plan on the same desktop with computer simulation

of the intended plan (figure 1). Once the surgeon is satisfied with his plan, he approves the plan, and a jig is then customised based on his plan. This jig is unique to that patient, and is unique to the plan made for the surgery (figures 2 and 3).

OUTCOMES OF PATIENT-SPECIFIC INSTRUMENTATION In a comparison of 569 knee surgeries with PSI and 155 with manual instrumentation, it was shown that the mechanical axis passed through the middle of the knee in 88% in the first group compared with 78% in the

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second.2 The authors also reviewed the literature and the compendium of a large number of studies from 2000 to 2011 showed that PSI resulted in knee misalignment (greater than 3) in 10.2% and conventional TKA led to misalignment in 28.3%. They concluded that PSI was helpful in achieving the correct axis. Another group of researchers measured the femorotibial angle in 50 patients who underwent knee arthroplasty with conventional instrumentation, 50 with PSI restoring the mechanical axis and 50 with PSI restoring the kinematic axis, all by two surgeons. They found that groups 1 and 2 had a similar number of outliers, with more varus outliers than group 3, which had more valgus outliers.3 The same author performed another small study (with 57 patients

in each arm) and showed that the use of PSI led to shorter time in the operating theatre compared to conventional instrumentation (137.2 versus 125.1 minutes).4 CONCLUSION Tan Tock Seng Hospital is the pioneer for PSI surgery in this region. I performed the first case in November 2010, and now we routinely perform about 16 such cases every month. Our TTSH MRI centre was also the first in this region to be certified competent in performing MRI scans for PSI. The additional cost for such jigs and an MRI scan is below $2000. It is certainly worthwhile, considering the surgery can be performed faster, safer, less invasive, and with improved accuracy.

Dr Teo Yee Hong is a consultant in the Department of Orthopaedic Surgery, Tan Tock Seng Hospital. He is also the Chief of the Adult Reconstruction Service.

References 1. Fang DM, Ritter MA, Davis KE. Coronal alignment in total knee arthroplasty: just how important is it? J Arthroplasty 2009; 24(6 Suppl):39-43. 2. Ng VY, DeClaire JH, Berend KR, Gulick BC, Lombardi AV Jr. Improved accuracy of alignment with patient-specific positioning guides compared with manual instrumentation in TKA. Clin Orthop Relat Res. 2012; 470:99-107. 3. Nunley RM, Ellison BS, Zhu J, Ruh EL, Howell SM, Barrack RL. Do patient-specific guides improve coronal alignment in total knee arthroplasty? Clin Orthop Relat Res 2012; 470:895-902. 4. Nunley RM, Ellison BS, Ruh EL, Williams BM, Foreman K, Ford AD, Barrack RL. Are patient-specific cutting blocks cost-effective for total knee arthroplasty? Clin Orthop Relat Res 2012; 470:889-94.

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Cases we saw in the

Quiz

clinics and wards, part 3


When we started this series a few years ago, we were afraid that we would run out of cases. We need not have. We kept seeing interesting patient and situations, and we kept learning new lessons. We share what we have learnt with you through these mini-quizzes. These clinical situations have challenged us. They vary in difficulty but we know they will all be educational. We hope that you benefit from the lessons of these patients and when you encounter similar cases in the future, the diagnosis will come to you in a snap. These real-life cases are not idealized examples. Youll notice that they are not clear-cut and they may present conflicting clinical signals. To maximize the benefit of this exercise, we again suggest that you tackle all the cases in sequence and write your answers on a piece of paper before looking at the solutions. CASE 1 In May 2010, this 60-year-old lady was hospitalized for the treatment of intestinal obstruction due to adhesions as a complication of open cystectomy performed five months ago. She had a complicated medical history. She received cyclophosphamide for the treatment of systemic lupus erythematosus, specifically transverse myelitis, intermittently from 1986 to 2005. She had also been receiving warfarin for many years for the antiphospholipid syndrome. She developed right breast cancer in 2005 and was treated with mastectomy and chemotherapy. Unfortunately, investigations for persistent pyuria in 2009 showed that she had developed bladder carcinoma, a known adverse effect of cyclophosphamide treatment. Anticoagulation was properly reversed prior to surgery. Laparotomy with adhesiolysis was performed on 23 May 2010. Suddenly, early in the morning on 27 May, she developed tachypnoea and tachycardia (sinus rhythm 130 per minute,). The haemoglobin concentration just dispatched that morning returned 8.4 g/dl (the table shows the haemoglobin concentration over the preceding days). The Cardiologist was consulted and he was intently looking at the ECG when you arrived. The surgeon reassured you that the patient is not bleeding. What do you think happened?

Table 1. Haemoglobin concentrations for the week preceding the acute event.

CASE 2 This 77-year-old lady was hospitalized for sudden-onset fever and lethargy. She is suffering from rheumatoid arthritis, hypertension and hypercholesterolaemia and was receiving subcutaneous etanercept, methotrexate, sulphasalazine, low-dose prednisolone, nifedipine and atenolol. There was no recent travel or ingestion of raw food. There were no signs to locate sepsis; there was no photophobia, cough, facial pain, abdominal pain, diarrhea or skin signs. She was toxic and the blood pressure was 100/80 mmHg with pulse 110. The temperature was 40 C. There was no neck stiffness. The heart, lungs and abdomen were normal. The joints were not inflamed. There was no rash or cellulitis. The haemoglobin was 11.6 g/dl (11.0 to 15.0), total white 10,000/mm (3,600 to 9,300), platelet 150,000/mm3 (170,000 to 420,000). The serum sodium was 133 mmol/l (our laboratorys reference range is 125 to 135), potassium 3.5 mmol/l (3.5

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to 5.0), creatinine 74 umol/l (40 to 75), urea 5.8 mmol/l (2.9 to 9.3), albumin 34 g/l (35 to 48), bilirubin 17 umol/l (7 to 31), ALT 41 u/l (15 to 54), AST 72 u/l (15 to 41), alkaline phosphatase 76 u/l (38 to 126), gamma-glutaryl transferase 43 u/l (7 to 50). The chest X-ray and urinalysis were unremarkable. Blood culture was pending. What is your diagnosis? What investigations would you order? CASE 3 A 72-year-old woman complained of breathlessness on exertion for the past six months. She used to exercise on the treadmill but now found that walking up the ramp left her winded. There was mild weight loss of 1-2 kg. She is known to be suffering from hypertension and mild renal impairment. She had undergone arthroplasty of the hips for osteoarthritis a few years ago. The haemoglobin was 9.2 g/dl, total white 6,200/mm3, platelet 357,000/mm3 and ESR 95 mm per hour. The serum creatinine was 145 umol/l. The chest X-ray was normal. The blood cultures were negative and serum protein electrophoresis did not yield any monoclonal band. What are your differential diagnoses? CASE 4 This 50-year-old lady experienced right flank colic in October. By December, she felt better. She was reviewed by her Urologist who ordered these scans (figure 1). Together, they tell a coherent story. What do you see?

Figure 1. This series shows a single view taken from each of three CT kidney-ureter-bladder scans performed on 10 May, 17 November and 2 December.

CASE 5 This 67-year-old lady slipped and fell on the wet flood injuring the left parietal region. This is one of the X-rays taken after the fall (figure 2). What clinical signs do you expect to find?

Figure 2. This is an X-ray of the lateral view of the neck. Do you see any abnormality?

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CASE 6 This 71-year-old lady was hospitlaised for the complaint of cough of a weeks duration. There was marked decrease of chest movement on the left side. This is her chest X-ray (figure 3). Will you put her in an isolation room?

Figure 3. Chest radiograph of an elderly lady. What should you be wary of?

CASE 7 A 75-year-old man with multi-infarct dementia was admitted to hospital for urinary sepsis. He developed right upper arm and elbow swelling two days after admission, though he could not complain because of his mental state. The X-ray of the right humerus was taken. How did this sign develop?

Figure 4. X-ray of the right humerus of an elderly bed-ridden man with dementia. What caused this abnormal finding?

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CASE 8 This 64-year-old lady has been suffering from epigastric discomfort for six months. Endoscopy and blood tests were normal. Barium swallow in March 2011 showed severe gastro-oesophageal reflux. Oesophago-gastroscopy in April 2011 only revealed mild reflux oesophagitis. The symptoms did not abate and she was hospitalized because of vomiting and loss of appetite. She was diagnosed to have subacute intestinal obstruction. In October 2011, a diagnostic laparoscopy did not reveal any reason for the obstruction. CT scan of the abdomen was performed. What do you see and what is a possible diagnosis? The patient passed away a few days after the scan was taken.

Figure 5. What dangerous sign you see in the CT scan of the abdomen? What is the underlying cause?

CASE 9 This 60-year-old lady complains of pain over the left heel, at the insertion of the tendoachilles, for the past two years (figure 6). There was no trauma. Clinically, there was swelling over the calcaneum but the tendoachilles itself was normal. The patient had no problems walking or standing on the ball of her foot. The ESR was 15 mm per hour. Do you agree with the diagnosis of Achilles tendonitis due to seronegative spondyloarthropathy?

Figure 6. Picture of the left foot showing the prominent bony swelling at the heel. An X-ray of the same region is shown on the right.

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CASE 10 This 58-year-old lady developed acute backache and a lumbosacral spine X-ray was ordered (figure 7). These images were returned. Do the findings explain the pain?

Figure 7. Lumbosacral X-ray of a 58-year-old lady.

SOLUTIONS
CASE 1 The patient in fact developed intra-abdominal haemorrhage. At your insistence, the full blood count was sent off again. This case reminds us not rely on others but to examine the evidence and judge for ourselves. In acute bleeds, the haemoglobin concentration remains the same as baseline because whole blood is lost. The haemoglobin concentration only falls when volume is restored, either through the bdoys homeostatic mechanism or through fluid resuscitation, as in this case. The repeat haemoglobin was 4 g/dl (table 2).

Date 21 May 22 May 23 May 23 May 24 May 25 May 27 May 27 May 27 May 27 May 27 May 28 May 28 May

Time 12:26 pm 9:19 am 6:40 am 11:31 pm 8:58 am 11:47 am 7:20 am 9:25 am 9:46 am 1:44 pm 9:11 pm 4:00 am 3:58 pm

Haemoglobin (g/dl) 11.7 10.7 9.3 11.3 8.8 9.9 8.4 4.0 3.8 8.7 9.1 9.4 9.9

Table 2. Extended list of haemoglobin levels. Note the remarkable fall in haemoglobin concentration on 27 May.

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CASE 2 A patient receiving etanercept, methotrexate and prednisolone (all immunosuppressive drugs) is predisposed to infections. Therefore, sepsis must be ruled out. Commonly infected sites are the lungs, urinary tract, hepatobiliary system and the skin. In the vignette, the lungs, urinary system and skin have reasonably been excluded as sites of infection. That leaves the hepatobiliary system. Though the liver function tests were fairly normal, CT scan of the abdomen was ordered to exclude liver or splenic abscess; the former was found (figure). The blood culture returned E. coli.

Figure 8. These images taken from CT scan of the abdomen (coronal sectional on the right and transverse on the left) reveal a liver abscess (arrows).

CASE 3 For an older person with constitutional symptoms, elevated ESR, the differential diagnoses include sepsis (which may be occult, such as in the prosthetic joints), myeloma and other occult malignancies, and connective tissue diseases such as lupus, Sjogrens syndrome and polymyalgia rheumatica. Unfortunately, the patient had to undergo an extensive series of tests to work through these differential diagnoses. Eventually, after excluding all the serious diagnses, we concluded that she was suffering from polymyalgia rheumatica. A therapeutic trial of corticosteroid made the patient feel better, as well as reducing the ESR and raising the haemoglobin level. CASE 4 The first image shows a radio-opaque calculus in the right renal pelvis. As it begins to migrate downwards, right hydronephrosis and hydroureter developed. The stone is not visible in the second image. In the third image, the hydronephrosis and hydroureter have resolved, and the stone is now found in the right distal ureter. CASE 5 There is a fracture through the odontoid process. The patient has signs of spastic quadriparesis.

Figure 9. Comparison of the plain X-ray and MRI of the cervical spine. The fracture across the odontoid process is indicated by the arrowhead in the MRI image. There is compression of the spinal cord at that level too.

CASE 6 This is one of the rare patients in our era who has fibrothorax due to tuberculosis. She was treated 30 years ago with a two-year course of oral medication. Fortunately, the sputum smears did not show any acid-fast bacilli and she was soon discharged. The diagnosis was upper respiratory tract infection.

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CASE 7 There is a fracture in the right humerus at the junction of the upper 1/3 and lower 2/3. Compared to fractures of the vertebra, distal radius or femoral neck, this is a little-known osteoporotic fracture.1,2 This relatively common injury happens in bed-ridden patients with shoulders fixed in adduction as care-providers lift them by abducting their arms. CASE 8 The CT scan shows air in the intestinal wall, or pneumatosis coli, a dire radiological sign. The patient had chronic mesenteric ischaemia that eventually went into an acute phase with acute ischaemia. As demonstrated in this case, the diagnosis is very difficult.3 Patients commonly present with pain 15 to 60 minutes after eating, and some patients will develop fear of eating. When the disease progresses, the pain may become persistent. Given the clinical context, a differential diagnosis is amyloidosis of the intestines due to rheumatoid arthritis, though this is very rare indeed.4 CASE 9 The lack of inflammation and the knowledge of a condition that can explain the clinical signs mean that we do not have to say that the patient has seronegative spondyloarthropathy. The patient has a soft tissue swelling at the insertion of the Achilles tendon at the heel; she has Haglunds syndrome.5 This condition is not rare; it is thought to be due to retrocalcaneal bursitis due to rigid low-back shoes in people who happen to have prominent bursal projection. Figure 10 below shows the prominent posterosuperior calcaneal (bursal) projection (V); the horizontal Vs indicate swelling of the retro-Achilles bursa.6 The inferior calcaneal spur is incidental. There is calcification of the insertion of the Achilles tendon but it is not a requirement for diagnosis of Haglunds syndrome.

Figure 10. Lateral X-ray of the left calcaneum indicating the bursal calcaneal projection (V) and soft tissue swelling of the retro-Achilles area (horizontal Vs).

CASE 10 There are many calcified lymph nodes due to past intra-abdominal tuberculosis. The findings do not explain the back pain. Indeed, in patients with backache without neurological deficits and lacking the red flags of serious pathology, imaging studies are not indicated.7
References

1. Hertel R. Fractures of the proximal humerus in osteoporotic bone. Osteoporos Int 2005; 16 Suppl 2:S65-72. 2. Martin-Hunyadi C, Heitz D, Kaltenbach G, Pfitzenmeyer P, Mourey F, Vogel T, Niederberger B, Kiesmann M, Berthel M, Kuntzmann F. Spontaneous insufficiency fractures of long bones: a prospective epidemiological survey in nursing home subjects. Arch Gerontol Geriatr 2000; 31:207-214. 3. Hohenwalter EJ. Chronic mesenteric ischemia: diagnosis and treatment. Semin Intervent Radiol 2009; 26:345-51. 4. Morrison WJ, Siegelman SS. Pneumatosis intestinalis in association with connective tissue disease. South Med J 1976; 69:1536-9. 5. Avarez-Nemegyi J, Canoso JJ. Heel pain: diagnosis and treatment, step by step. Cleveland Clin J Med 2006; 73:465-71. 6. Koulouris G, Morrison WB. Foot and ankle disorders: radiographic signs. Semin Roentgenol 2005; 40:358-79. 7. Qaseem A, Alguire P, Dallas P, Feinberg LE, Fitzgerald FT, Horwitch C, Humphrey L, Leblond R, Moyer D, Wiese JG, Weinberger S. Appropriate use of screening and diagnostic tests to foster high-value, cost-conscious care. Ann Intern Med 2012; 156:147-149.

Dr Leong Khai Pang is a senior consultant in the Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital.

Dr Gervais Wan is a senior consultant in the Department of Diagnostic Imaging, Tan Tock Seng Hospital.

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Supplementation in

Pharmaceutical Update

Nutritional Anaemia
Anaemia is a prevalent condition with a variety of underlying causes. Using the World Health Organization definition of anaemia (haemoglobin level less than 13 g/dL in men and less than 12 g/dL in women), more than 10% of persons older than 65 years are anaemic. In the United States, data have shown that anaemia risk increases with age. In the group of people aged 65 to 69 years, the incidence of new-onset anaemia was 6% in men and 4% in women.1 In persons 85 years and older, the annual incidence rose to 14% in men and 13% in women. In Singapore, retrospective studies have reported up to 57% prevalence of anaemia in hospitalized elders, with 26 to 30% attributed to nutritional deficiencies.2,3

CLINICAL PRESENTATION Anaemia often has an insidious onset in the elderly. Acute drop in haemoglobin may cause dizziness and falls while slower onset of anaemia is better tolerated, and symptoms develop only as compensatory mechanisms fail. Patients with pre-existing cardiac diseases often become more symptomatic as haemoglobin level decreases. Typical symptoms of anaemia, such as fatigue, weakness, dyspnoea, and pallor may not be specific.4,5 LABORATORY TESTS A complete blood count and iron studies are useful in determining the extent and type of anaemia. The mean corpuscular volume (MCV) is used to distinguish microcytic, normocytic, and macrocytic anaemia. Peripheral blood smear and reticulocyte count are also useful tests for classification of anaemia. Folate and vitamin B 12 levels can be used for detecting deficiencies. Serum folate level (reference range 8 to 48 nmol/L) can be performed. Serum cobalamin level <200 pg/ mL is 95% specific for clinically overt deficiency. These serum laboratory tests together with clinical manifestation are useful differential diagnostic tools.6 However, do note that different laboratories may offer slightly different reference ranges due to variations in the equipment and test kits. The algorithm presented as figure 1 can guide physicians in differentiating the aetiologies of anaemia as the treatment varies.4,5

This article will focus on the management of three common types of anaemia requiring supplementation, namely, irondeficiency, folate-deficiency and vitamin B12-deficiency anaemia. Treatment modalities such as blood products transfusion and erythropoiesis-stimulating agents will not be discussed here. IRON-DEFICIENCY ANAEMIA Iron-deficiency anaemia (IDA) is the most common form of nutritional anaemia, with a prevalence of 16.6% in non-institutionalized elders

aged 65 and above in America.1 Locally, 13% of anaemia cases in hospitalized elderly were attributed to iron deficiency.3 It leads to hypochromic and microcytic anaemia with commonly presenting with pallor, fatigue, dyspnoea and palpitation. Atrophic glossitis and dysphagia can occur too. Causes Iron deficiency should be distinguished from other causes of anaemia because of its associations with underlying conditions that mandate specific investigation.

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Figure 1. Algorithm for the diagnosis of anaemia

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Treatment is also simple, safe and effective. The main causes of IDA are blood loss, dietary insufficiency and malabsorption. Blood loss (secondary to cancer, colitis, drugs such as steroids and non-steroidal anti-inflammatory drugs, for example) is the most important cause of iron deficiency in adults. Malabsorption of iron may be caused by intestinal mucosal disorders, impaired gastric acid secretion (including use of proton pump inhibitors), and gastric/ intestinal bypass procedures. Helicobacter pylori colonization is also associated with IDA and may impair iron uptake and increase iron loss in humans.7 Once the underlying cause of iron deficiency has been determined, it must be addressed and iron replacement therapy can be initiated. The aim of treatment should be to restore haemoglobin level and MCV to normal and replenish body stores of iron. Iron supplementation (oral) Common available oral preparations include ferrous sulphate (20% elemental iron), ferrous gluconate (12% elemental iron) and ferrous fumarate (33% elemental iron). Given at equivalent elemental iron doses, different oral iron salts have similar efficacy and tolerability.8 The usual recommended dose for IDA is 100 to 200 mg of elemental iron in 2 to 3 divided doses to reduce side effects such as nausea and vomiting. Taking iron supplements after meals can reduce nausea and vomiting but could compromise absorption. Therefore, it is recommended to take iron at least 30 minutes before food unless side effects are not tolerable. Slow titration by increasing 1 tablet or capsule per week to the tolerated or target dose may minimize gastrointestinal side effects. Constipation can be significant, and can be managed with laxatives or by using commercial iron products containing sorbitol (Sangobion for example). After receiving therapeutic doses of oral iron, reticulocytosis should occur within 72 hours, and haemoglobin levels should rise by about 1 to 2 g/ dL every 3 weeks. Repletion may take 4 to 6 months and it is reasonable to continue replenishing for 3 to 6 more months following normalization

of haemoglobin. In patients where deficiency is likely to recur (malnutrition, chronic gastrointestinal diseases), maintenance therapy with 65mg of elemental iron daily is recommended.8,9

Gastrointestinal absorption of elemental iron is enhanced in an acidic gastric environment. Addition of ascorbic acid can also be given for patients with poor response to oral iron. Food rich in tannates such as tea

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can induce binding of iron therefore reducing absorption. Medications that raise the gastric pH such as antacids, proton pump inhibitors, histamine H2 blockers can reduce absorption and should be avoided if not indicated.9 If a patient fails to respond to therapy, physician should re-evaluate the diagnosis, patients compliance and for on-going blood loss. Iron supplementation (parenteral) Indications for parenteral iron include: chronic uncorrectable bleeding; intestinal malabsorption; intolerance to oral iron, haemoglobin level less than 6g/dL with signs of poor perfusion in patients who would otherwise receive transfusion; and, chronic renal impairment receiving concomitant erythropoietinstimulating agent therapy.6,7,9 Although IM injection of iron is effective, it is painful, is associated with permanent skin staining and is not safer than IV infusion. The doses for IV iron are presented in table 1.10-12 Iron dextran, despite its longest history of use in patients with anaemia, is not commonly used due to the association with life-threatening anaphylaxis reaction. Small test doses are therefore recommended when patient is newly initiated on IV iron therapy. Patients receiving regular IV iron should be monitored closely for clinical or laboratory evidence of iron toxicity or overload. Abnormal liver function tests, a serum ferritin greater than 800 to 1000 mcg/L, or transferrin saturation greater than 50% may all indicate iron overload. Serum ferritin and transferrin saturation should be measured at least one week after administration of IV iron for modest doses (100 to 200 mg) and at least two weeks after IV iron for larger doses, in order to exclude a spuriously high measurement.13 FOLATE-DEFICIENCY ANAEMIA Folate-deficiency anaemia (FDA) leads to macrocytic, normochromic anaemia that occurs in about 6% in the elderly in America and up to 9% in local hospitalized elders.2-4 Humans do not generate folate endogenously and it has to be obtained from dietary sources. A healthy individual has about 500 to 20,000 mcg of folate in

body stores. Humans need to absorb approximately 50 to 100 mcg of folate per day in order to replenish the daily degradation and loss through urine and bile. Otherwise, signs and symptoms of deficiency can manifest after 4 months.14 Some patients complain of a sore tongue or pain upon swallowing. Angular stomatitis may be observed. Patients may present with gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and diarrhoea, especially after meals. Anorexia, in combination with the above symptoms, may lead to marked weight loss. Patchy hyperpigmentation on the skin and mucous membrane can occur, but usually resolves after folate treatment. Causes Elderly people may be more susceptible to folate deficiency because of their predisposition to mental status changes, social

isolation, low intake of leafy vegetables and fruits, and comorbid medical conditions. Very often, folate-deficient patients have a history of excessive alcohol intake with concurrent poor diet. Folate is destroyed by prolonged exposure to heat; over-cooking food in boiling water may predispose to deficiency. Iatrogenic causes can be significant too. Drugs such as phenytoin, sodium valproate and methotrexate are wellknown culprits. Medical conditions such as coeliac disease, short bowel syndrome, hypothyroidism, haemolytic anemia, vitamin B12 deficiency, pregnancy and lactation could also lower folate level through decreased absorption, increased utilization and destruction.14 Folate supplementation The minimal daily requirement is about 50 mcg. No clear guidelines exist for the appropriate formulation, dose or duration of folate replacement. The usual dose for megaloblastic

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Common regimens and the duration of repletion for vitamin B12 replacement are presented in table 2.20,22 Some common oral preparations available commercially are presented in table 3.15 Vitamin B12 is generally safe. Pain and redness at the injection site and anaphylactic reactions (for parenteral injections), mild gastrointestinal side effects like diarrhoea, nausea, vomiting and dyspepsia, dermatological effects such as itching, rosacea and exanthema may occur. The dermatological manifestations may persist for up to months after the supplement is stopped and may require treatment with systemic corticosteroids and topical therapy.

Correction of megaloblastic anaemia can also result in polycythemia vera and hypokalemia. Increased blood viscosity as well as intracellular potassium shift is the result of increased red blood cell production in the body following replacement.24 CONCLUSION Anaemia is more prevalent in the aged may have serious health consequences. Nutritional anaemia can be easily treated with the appropriate type of supplementation if an accurate diagnosis is made and underlying causes addressed. Treatment is often affordable, and side effects are minimal and usually well tolerated by patients.

Ms Selina Cheong is a Pharmacist in the Department of Pharmacy, Tan Tock Seng Hospital.

References
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. Ania BJ, Suman VJ, Fairbanks VF, Rademacher DM, Melton LJ, 3rd. Incidence of anemia in older people: an epidemiologic study in a well defined population. J Am Geriatr Soc 1997; 45:825-31. Sahadevan S, Choo PW, Jayaratnam FJ. Anaemia in the hospitalised elderly. Singapore Med J 1995; 36:375-8. Rong MJT, Yong YO. Prevalence and risk factors of anaemia in older hospitalised patients. Proceedings of Singapore Healthcare 2011; 20:71-9. Bross MH, Soch K, Smith-Knuppel T. Anemia in older persons. Am Fam Physician. 2010; 82:480-7. Smith DL. Anemia in the elderly. Am Fam Physician 2000; 62:1565-72. Durso SC, Bowker LK, Price JD, et al. Oxford american handbook of geriatric medicine. 1st ed. New York, NY: Oxford University Press; 2010. Pasricha SR, Flecknoe-Brown SC, Allen KJ, et al. Diagnosis and management of iron deficiency anaemia: a clinical update. Med J Aust 2010; 193:525-32. Little DR. Ambulatory management of common forms of anemia. Am Fam Physician. 1999; 59:1598-604. Killip S, Bennett JM, Chambers MD. Iron deficiency anemia. Am Fam Physician. 2007; 75:671-8. Drugs information online. Iron dextran monograph. http://www.drugs.com/dosage/iron-dextran.html. Updated January 2012. Accessed February 15, 2012. Drugs information online. Sodium ferric gluconate monograph. http://www.drugs.com/ppa/sodium-ferric-gluconate.html. Updated January 2012. Accessed February 15, 2012. Drugs information online. Iron sucrose monograph. http://www.drugs.com/ppa/iron-sucrose.html. Updated January 2012. Accessed February 15, 2012. Fishbane S, Mittal SK, Maesaka JK. Beneficial effects of iron therapy in renal failure patients on hemodialysis. Kidney Int Suppl. Mar 1999;69:S67-70. Medscape reference online. Folate deficiency anemia. http://emedicine.medscape.com/article/200184-overview#a0104. Updated December 2011. Accessed January 6, 2012. MIMS Singapore. http://www.mims.com.sg/Singapore4-overview#a0104. Updated December 2011. Accessed December 15, 2011. Drugs information online. Folic acid monograph. http://www.drugs.com/pro/folic-acid.html. Updated December 2011. Accessed Decemeber 15, 2011. Butterworth CE, Jr., Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr 1989; 50:353-8. Medscape reference online. Folic acid monograph. http://reference.medscape.com/drug/folvite-folic-acid-344419. Updated December 2011. Accessed Feburary 19, 2012. Medscape reference online. Pernicious anemia. http://emedicine.medscape.com/article/204930-overview. Updated December 2011. Accessed January 6, 2012. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician 2003; 67:979-986. Andres E, Dali-Youcef N, Vogel T, Serraj K, Zimmer J. Oral cobalamin (vitamin B(12)) treatment. An update. Int J Lab Hematol 2009; 31:1-8. Andres E, Loukili NH, Noel E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ 2004; 171:251-259. Butler CC, Vidal-Alaball J, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Fam Pract 2006; 23:279-285. Merck Manual Online. Vitamin B 12 deficiency. http://www.merckmanuals.com/professional/nutritional_disorders/vitamin_deficiency_dependency_and_ toxicity/vitamin_b12.html. Updated Feburary 2007. Accessed Feburary 19, 2012.

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RADIOLOGY Quiz
A 53-year-old lady presented with progressive skin tightening with areas of hypo- and hyperpigmentation. This was associated with swelling of her hands and feet and Raynauds phenomenon. The aperture of her mouth also decreased. No dysphagia or shortness of breath was reported at presentation. Radiographs of her hands and chest ordered at presentation showed no abnormality except for soft tissue thinning. She did not return for follow-up until seven years later when she developed bilateral lower limb vasculitic ulcers. A radiograph of both hands and a high resolution CT (HRCT) if the thorax were performed.

Figure 1. X-ray of both hands

Figure 2. A section of the high-resolution scan of the thorax

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QUESTIONS
1. Describe the abnormalities seen in the hands on plain radiograph. 2. What are the differential diagnoses? 3. What abnormalities (arrows) are present in the cross-sectional image of the lungs on HRCT?

ANSWERS
1. There is acro-osteolysis (distal tuft resorption) with penciling, sharpening and complete loss of bony cortex in the fingers with relative sparing of the right little finger. There are no significant bony erosions except in the base of the left fourth metacarpal. There is reduction of the carpometacarpal and intercarpal joint spaces. Mild periarticular osteopenia is present. There is atrophy of the overlying soft tissues especially over the proximal phalanges. There is also subluxation of the left first metacarpo-phalangeal joint. An old non-united fracture is present at the proximal phalanx of right little finger. 2. The most obvious abnormality on the hand radiograph is acro-osteolysis. Differential diagnoses of resorption of the distal phalanges include scleroderma, psoriasis, peripheral vascular disease, frostbite, tabes dorsalis and hyperparathyroidism. 3. The HRCT shows ground glass opacities in a subpleural location in both lower lobes in keeping with early interstitial fibrosis.

Discussion
In this patient, acro-osteolysis was the most prominent imaging finding. Absence of underlying risk factors makes peripheral vascular disease, frostbite and tabes dorsalis unlikely. Typical associated features of hyperparathyroidism such as subperiosteal cortical resorption and diffuse osteopenia were absent. Soft tissue atrophy and thinning as well as relative lack of joint destruction favour scleroderma over psoriasis. The patient also shows features of early interstitial lung disease on the HRCT scan. There was no significant gastrointestinal manifestation of systemic sclerosis other than for severe gastroesophageal reflux. Subsequent laboratory investigations revealed positive antinuclear and antiScl-70 antibodies, supporting the diagnosis of diffuse scleroderma. The patient was treated with prednisolone and methotrexate. A barium meal was performed to evaluate for apparent dysphagia. This showed severe gastroesophageal reflux but no apparent esophageal dilatation. Scleroderma is a connective tissue disease of unknown aetiology with fibrosis and skin tightening. The three subtypes of scleroderma are diffuse, limited and scleroderma sine scleroderma. In the diffuse form, otherwise known as systemic sclerosis, there is involvement of internal organs such as the heart, lung, kidneys and gastrointestinal tract. The peak age of onset is from 30 50 years old. The disease occurs in women four times more commonly than in men. Patients with scleroderma sine scleroderma develop internal organ involvement without skin signs. Radiological manifestations of scleroderma in the musculoskeletal system include acro-osteolysis, periarticular osteopenia, joint space narrowing and soft tissue (subcutaneous and periarticular) calcifications.1 Bone resorption frequently occurs in the distal phalanges but it can also occur in other osseous structures such as the angle of mandible, distal radius

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and ulna.2 Other non-specific signs included erosions in the superior aspects of the posterior ribs. Soft tissue calcifications reflect a response to tissue damage. They are frequently seen in the fingertips, though they may also occur in any location, even within joints. Compared to hand involvement, foot involvement is less frequent. It occurs later in the disease process but is equally disabling. Pulmonary involvement is demonstrated histologically in 90% of patients with scleroderma. It is the leading cause of disease specific mortality. Chest radiographs are not sensitive to early changes of interstitial lung disease and may appear normal despite restrictive lung disease. HRCT is considered the most sensitive imaging modality for detection of early pulmonary involvement. Scleroderma may present with either a usual interstitial pneumonitis (UIP) or nonspecific interstitial pneumonitis (NSIP) pattern. UIP and NSIP are subgroups of interstitial lung disease. UIP typically manifests as subpleural reticular changes while NSIP usually presents as ground glass and reticular opacities. Although the presence of honeycomb changes as the predominant finding makes UIP more likely, surgical biopsy may still be needed for definitive diagnosis.3 Gastrointestinal manifestations of scleroderma can occur in up to 90% of patients suffering from scleroderma. The oesophagus is the commonest site of gastrointestinal involvement (80%). Radiographic features include dilatation and dysmotility of distal two-thirds of the oesophagus with normal peristalsis above the aortic arch.4 In late stages, there can be shortening of the esophagus due to fibrosis. Gastroesophageal reflux occurs due to reduced sphincter tone. The small bowel is affected in more than 60% of scleroderma patients, most commonly in the duodenum. Radiological features include luminal

dilatation (which can be massive), and reduced peristalsis with consequent delayed transit.5 Interestingly, the mucosal folds are relatively preserved despite the degree of dilatation. In fact, there is crowding of valvulae conniventes, termed the hidebound bowel sign on small bowel barium studies. Sacculation is also a prominent feature and is thought to be a result of focal dilatations and pseudo-diverticula. This typically occurs along the antimesenteric border. The large bowel is affected in about 40% of scleroderma patients with the radiologic feactures of pseudosacculation, loss of haustration, colonic dilatation and reduced colon transit time. MANAGAMENT Treatment is very difficult and is aimed at controlling the autoimmune and inflammatory components of the disease. Skin tightening and interstitial lung disease can be controlled by immunosupressants such as interferon-gamma, mycophenolate mofetil, and cyclophosphamide. Photopheresis and allogeneic bone marrow transplant have also been considered.6 Pruritus can be managed symtomatically with moisturisers and antihistamines. Raynauds phenomenon can be treated with vasodilators such as calcium channel blockers, prazosin, prostaglandin E1, dipyridamole and with analgesics (aspirin and topical nitrate). Gastrointestinal manifestations can be managed symptomatically with antacids, proton-pump inhibitors and prokinetic agents. Myalgias and arthralgias are managed with NSAIDs, steroids, azathioprine or methotrexate. Long-term follow up is usually required in this debilitating progressive autoimmune disease. The prognosis of the disease depends on the type

of scleroderma. In diffuse type, the disease can lead to death, if not treated promptly.

References 1. Baron M, Lee P, Keystone EC. The articular manifestations of progressive systemic sclerosis (scleroderma). Ann Rheum Dis 1982; 41: 147-52. 2. Bassett LW, Blocka KL, Furst DE, Clements PJ, Gold RH. Skeletal findings in progressive systemic sclerosis (scleroderma). AJR Am J Roentgenol 1981; 136:1121-6. 3. Elliot TL. High resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia. J Comput Assist Tomogr 2005; 29: 339-45. 4. Bhalla M, Silver RM, Shepard JA, McLoud TC. Chest CT in patients with scleroderma: prevalence of asymptomatic esophageal dilatation and mediastinal lymphadenopathy. AJR Am J Roentgenol 1993; 161:269-72 5. Jaovisidha K, Csuka ME, Almagro UA, Soergel KH. Severe gastrointestinal involvement in systemic sclerosis: report of five cases and review of the literature. Semin Arthritis Rheum 2005; 34:689-702. 6. Nihtyanova SI, Denton CP. Current approaches to the management of early active diffuse scleroderma skin disease. Rheum Dis Clin North Am 2008; 34:161-79; viii.

Dr Ng Chee Hui is a medical officer at the Department of Diagnostic Radiology Tan Tock Seng Hospital

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ECG Quiz
QUESTION
This 73-year-old female presented with sudden-onset palpitation. This is her ECG. The heart rate is 120. Is this ECG normal? Is this normal sinus tachycardia?

ANSWER

This ECG is abnormal. If you look carefully, the P waves are not discernible. In fact, the P waves are inscribed at the end of the preceding QRS complex. This is manifested as an S wave of the QRS complex in the inferior leads and a R wave in lead V1. This is called pseudo S and pseudo R waves in the inferior and V1 leads respectively as this phenomenon is absent in the normal 12-lead ECGs. The entire ECG is a manifestation of supraventricular tachycardia with a heart rate of 120. This was terminated with intravenous adenosine. The subsequent normal 12-lead ECG is shown as below.

Dr David Foo is the Head of the Department of Cardiology, Tan Tock Seng Hospital.