Answer To June 2009 Case

Dear Bloggers

Welcome back. Today I will discuss the answer to the recent case. This was one of the most difficult cases I have ever experienced and I thought it would be nice to share this with you all. I was reminded by a colleague also involved with the case, that the rash was in fact painful rather than painless and hence, the initial description of her symptoms was inaccurate for which I apologise :-o

Professor Matsumura has kindly provided his opinion on the case (see below) in respect of the revised history of the patient. His ideas were very much in keeping with the team looking after the patient on initial presentation.

The patient was a 43-year-old woman. I would describe problem list first.

Problem list

#1 Skin rash

The lesions were circular, purplish, discrete, raised with an umbilicated central area. The lesions began as smaller discrete nodules that rapidly expanded. After several days, existing lesions developed a necrotic centre with circumferential erythema. The lesions eventually crusted over leaving large areas of eschar.

#2 Fever

#3 Tachycardia

#4 History of right breast cancer

#5 Acyclovir and ciprofloxacin administration

The main problem of this patient is fever and rash. Differential diagnosis is broad in fever and rash. However, I would think three main category, infection, neoplastic, and autoimmune. Characteristics of skin rash are likely infectious disease. Neoplastic or autoimmune is less likely. But neoplastic disease should be considered for background of this patient

Questions:

1) From the history and physical examination what would be your likely differential diagnosis?

Vascular: Less likely

Infection: Varicella, HIV, molluscum contagiosum, disseminated cryptococcosis, eosinophilic folliculitis, cutaneous anthrax

Neoplastic: (Recurrence of breast cancer)

Autoimmune: Sarcoidosis

Toxic: Less likely

Metabolic: Less likely

Trauma: Less likely

Degenerative: Less likely

Iatrogenic: Less likely

Idiopathic: Less likely

Congenital: Less likely

I would think varicella is the most likely based on the character of skin rash. The problem is this patient was a 43-year-old woman. Varicella is common in children. Moreover, this patient had history of breast cancer and acyclovir administration.

2) What are the two most important tests to confirm the diagnosis?

Tzanck smear for detecting multinucleated giant calls.

Direct immunofluorescent antibody (DFA) staining.

3) What is your chosen treatment?

Depend on following assessment, question 4.

4) What addition problem should you consider screening for in this patient?

Interstitial pneumonia as complication of adult varicella should be carefully monitored. Cancer screening including recurrence of breast cancer should be evaluated. Moreover, I would confirm pregnancy test.

The Answer

The team caring for this patient were very concerned about an infectious disease such as varicella and even cutaneous anthrax, despite no history of there being any exposure to the latter infectious disease. Therfore, she was nursed with full barrier protection as a precautionary measure.

Her laboratory studies were normal except for a neutrophilia. Varicella IgG was present and IgM was absent suggesting previous infection. Autoimmune serology including ANCA was negative.

Blood cultures were negative.

The patient had the lesions tested for varicella zoster with viral cultures, which were negative.

Chest radiograph was normal.

CRP was 13.6 and ESR was 17mm/hr.

She developed secondary staphylococcal infection as evidenced by impetigo and positive skin cultures. She was commenced on ceftriaxone.

She was reviewed by the hospital infectious disease specialist and dermatologist respectively, who both considered infectious, autoimmune and primary dermatologic disease.

The dermatologist also considered Acute Febrile Neutrophilic Dermatosis (Sweet's Syndrome) in view of the presentation, background history, fever and neutrophilia.

The patient therefore underwent a skin biopsy which confirmed the histopathology consistent with Sweet's Syndrome. She also met the proposed criteria for Sweet's Syndrome (see below).

She was commenced on corticosteroids orally (Prednisolone 60mg per day) with resolution of her symptoms and the lesions over several days. She was discharged home with outpatient follow up.

In view of her history of metastatic breast cancer, a search for secondary causes of Sweet's Syndrome such as a recurrent malignancy, would have been considered appropriate.

Sweet's Syndrome

Described by Robert Sweet 1964: A reactive process characterised by the abrupt onset of tender red-to-purple circinate plaques.

Usually occur on the

• extremities
• head
• neck

and typically are accompanied by fever and peripheral neutrophilia.

Pathophysiology

Neutrophil mediated hypersensitivity reaction to systemic factors, which may include, haematologic disease, infection, or drug exposure.

Evidence suggests that Sweet’s Syndrome is a cytokine T-cell-mediated disease with secondary and only temporary activation and participation of neutrophils.

Primarily skin affected but lung and kidney can be involved.

Frequency

Uncommon condition; several hundred reported cases in literature ~2.7 cases/million (Scotland) Kemmett et al 1990

~10-15% cases in setting of malignancy (which includes recurrent breast cancer) but most cases are idiopathic and benign.

Females predominantly affected (F:M 2-3:1) esp. non-malignancy associated Sweet syndrome.

Age at onset

• Females 30-50
• Males 60-90

Causes

• Idiopathic (~70% cases)
• Haematologic Malignancy: CML, AML, MDS. Hodgkin disease, cutaneous T-cell lymphoma, NHL, multiple myeloma, and hairy cell leukemia.
• Non-Haematological Malignancy: Slight increase in genitourinary cancers, rectal cancer, oral / tonsilar cancer, breast cancer and osteosarcoma.
• Infection: Streptococcal pneumonia, Yersinia infection. Atypical mycobacteria.

Drugs

G-CSF- well established cause

Possibly
Septrin
all-trans retinoic acid
minocycline

Anecdotal - Limited reports of drug associations include
lithium
furosemide
hydralazine
carbamazepine
levonorgestrel/ethinyl estradiol.

Systemic Disorders

15% cases of Sweet’s Syndrome

Most common association
Crohn’s Disease
Ulcerative Colitis

Sjogren’s, Behcet’s, RA, SLE , undifferentiated connective tissue disease all associated with Sweet’s.

Proposed diagnostic criteria include the following:

Both major criteria must be met in addition to two of the four minor criteria.

Major criteria

1 Acute onset of typical skin lesions
2 Histopathological findings consistent with Sweet’s syndrome

Minor criteria

1 Fever > 38°C or general malaise
2 Association with malignancy, inflammatory disorder or pregnancy or antecedent respiratory or gastrointestinal infection
3 Excellent response to systemic corticosteroids or potassium iodide (KI)
4 Abnormal laboratory values at presentation (three of four required: ESR > 20 mm; leukocytes > 8000; neutrophils > 70%; positive C-reactive protein)

(Rook's Textbook of Dermatology, Seventh Edition)

Treatment

Steroids!! Usually Prednisolone 1.0mg/kg/day -> Lesions should resolve <14>

Other treatment modalities

• Colchicine 1.5 mg/day
• Dapsone 100-200 mg/day
• Clofazimine 200 mg/day
• Cyclosporin A 5-10 mg/kg/ body weight/day
• Indomethacin 50-100 mg/day
• Naproxen 750 mg/day
• Doxycycline 200 mg/day

von den Driesch P. 1994

Prognosis

• Outcome depends on the underlying condition
• Recurrence may occur in up to 50% of patients
• Most likely in cases associated with haematological malignancy or drug reaction.

Take Home Message

When you see a patient with an unusual condition such as this, please involve the dermatologist as soon as possible for advice on the likely cause and for a skin biopsy to be taken.

Without a biopsy, despite the best problem list and differential diagnosis it can be difficult to establish the diagnosis even for the best of diagnosticians.

Certainly the history of the acute onset, location and progression of the disorder help to point to Sweet's syndrome as a possible diagnosis but a skin rash with fever has a wide differential. Hence, a biopsy is the very best way to establish the cause -- tissue is the issue!

Much of dermatology is pattern recongition and it can be difficult even for most senior doctors.

I would like to thank Prof Matsumura for his excellent attempt at diagnosis in this rare case. His suggestions were very good and would have led to the diagnosis through a skin biopsy as inferred from the two tests proposed. Moreover, checking for recurrent cancer and pregnancy showed good lateral thinking and were correct. Well done.

A Case For June 2009: Back with a difficult case!

Dear Bloggers

I am so sorry I have not been keeping up the blog. Life has been somewhat busy ! However, I have a great case for you. Have a go at trying to answer it. Answers in the near future.

A 43 year old Caucasian hospital secretary presented to a hospital with the following:

• Skin rash
• Fever

The lady was usually in good health when she developed an acute rash that commenced on her neck, and progressed to her face, trunk and upper + lower extremities over several days.

The rash was not painful or itchy. She described the rash a 'spotty', 'red' and 'knobbly'.

She went to see her local doctor who thought she might have an infection and prescribed her oral aciclovir and ciprofloxacin. However, rather than the rash regressing, it progressed rapidly at the dismay of the patient. Two days after receiving the antimicrobial therapy the patient developed a low grade fever of 37.6 degrees. The patient attended her local doctor again who referred her to the internal medicine team of the general hospital.

Her only previous history had been a mastectomy for carcinoma of the right breast in 1995 with dissection of 1 lymph node. She had been treated post-operatively with radiotherapy and chemotherapy (chemoradiation). She had been deemed disease free at her last outpatient follow-up.

She had one child aged 10 years old born via a normal vaginal delivery. Her periods were regular every 28 days with 5 days bleeding. Her last menstrual period had been one week before (which had been normal) and she denied pregnancy. She used barrier contraceptive with her husband. She and her husband were monogamous.

She had otherwise been well with no recent infection. She had not traveled recently, there were no pets at home and no recent contact with animals. She had no contact with patients in the hospital where she was employed. Other members of her family were unaffected. She had no unusual hobbies.

She denied taking any medications, herbal supplements or over-the-counter (OTC) drugs prior to the onset of her symptoms. Her daily food intake had not changed. She denied using any new jewellery or washing powders.

She had no relevant family history. She was a non-smoker and drank alcohol only occasionally.

On review of systems, she denied any cardiovascular, respiratory, abdominal, musculoskeletal, urogenital, CNS-PNS or endocrine symptoms. She particularly denied weight loss, appetite change or night sweats.


On Examination


VITAL SIGNS: BP 120/80mmHg, Pulse 108 / min & regular, Respiratory Rate 14/min, T 37.4 degrees C, SpO2 98% breathing ambient room air.

GENERAL: Looked well but slightly shaky. No JACCOL

HEENT - Nil focal except for rash (see below). No goitre.

CVS - Pulse volume and quality: normal, JVP not elevated, no carotid bruits, No heaves or thrills, S1 + S2 present, No S3 or S4, gallop or pericardial rub. Peripheral pulses present throughout. No evidence of DVT in the lower limbs.

RESP: No tracheal tug or deviation. Normal chest expansion. Percussion resonant. Normal vesicular breath sounds.

ABDOMINAL: Soft, non-tender, no masses or organomegaly. No hernial orifices and no groin lymphadenopathy. Rectal exam was not performed.

BREAST EXAM: Left breast normal - no masses, no skin abnormality, no abnormal nipple discharge and no axillary lymphadenopathy. Right mastectomy scar present. No evidence of recurrence. No axillary lymphadenopathy.

SKIN: The following pictures show the rash. The lesions were circular, purplish, discrete, raised with an umbilicated central area. The maximum diameter was about 1cm. The lesions began as smaller discrete nodules that rapidly expanded -- please see the yellowish smaller nodules in the lower part of the picture (below)


After several days, existing lesions developed a necrotic centre with circumferential erythema. The lesions eventually crusted over leaving large areas of eschar from involuting coalesced lesions over the shoulders and proximal lower limbs. Fresh lesions continued to develop.


Questions:

1) From the history and physical examination what would be your likely differential diagnosis?

2) What are the two most important tests to confirm the diagnosis?

3) What is your chosen treatment?

4) What addition problem should you consider screening for in this patient?

Catastrophic Arthritis

The above photo was provided as an anonymous example of an all too common arthritic disease -- rheumatoid arthritis.

As can be seen the patient has boutoniere change in the left hand, ulnar deviation of the fingers from subluxation at the MCP joints.

There is also some telescopic changes of the fingers usually a feature of psoriatic arthritis. There were no psoriatic nail changes or skin abnormalities seen.

Elbows revealed RA nodules and dislocations. The shoulders were affected as were the knees, ankles and toes.

Despite these being 'classical signs' of RA, we should not be seeing this in this day and age. We should not be seeing this because there are very effective DMARDs available to suppress RA.

This patient, if newly diagnosed today would be started on methotrexate and the dose would very rapidly be titrated to the recommended dose of 15-25mg per week or maximum tolerated dose, with a starting dose of 7.5mg per week. Sometimes if oral MTX is not effective, subcutaneous administration is tried.

DMARD treatment should not be delayed. If the inflammatory changes can be suppressed within the first 6 months of symptoms onset (early RA) then the chronic debilitating features can potentially be avoided.

This patient was on combination treatment of methotrexate, bucillamine and prednisolone. However, the dose of MTX used in Japan is usually lower than that recommended in trials e.g. 4mg. Older 'add on' DMARD therapy such as bucillamine, the cousin of penicillamine, is also still used commonly.

With the advent of MTX, leflunamide and anti-TNF antibodies, the likes of penicillamine are now rarely used in the UK. However, occasionally, patients still use drugs such as anti-malarials (hydroxychloroquine) or sulfasalazine in the UK.

Patients should no longer get to a state of being disabled by an ultimately treatable condition.

There is a real need for more expertise in treating connective tissue diseases so that patients can be managed with the most effective drugs in line with current medical evidence.

The term 'burned out' RA which this patient might appear to have is a misnomer. RA is now considered to be a continuous disorder which does not burn out. Also, such patients have an increased risk of death compared to the rest of the healthy population. Hence, it is not merely an inconvenience, it increases morbidity and mortality.

The term of 'hit it hard and hit it fast' applieds to RA. If the therapy is delayed or insufficient to suppress the arthritis, patients can end up the very same as in the photo above.

Please read UpToDate 17.1 for the latest evidence on RA. Note that penicillamine is not recommended by UpToDate for modern treatment of RA.

Please consider.

-- Post From My iPhone

Translation of Pathology into Questions for History Taking

Dear Bloggers

I have often focused my blog articles on how to take a history. However, many junior residents come from medical school and are still uncertain how to ask the 'right' questions. It is not an easy thing being faced with a sick patient and then, miraculously knowing which questions to ask. However, in order to understand what questions we should ask in the very first place we need to fundamentally turn things upside down and think about the disease first and then work out what questions can stem from such diseases.

For example, a patient may present with chest pain. This should immediately make us consider the causes of chest pain that should never be missed, for example, acute coronary syndrome (ACS), aortic dissection, pulmonary embolism, pneumonia, pneumothorax, oesophageal rupture, to name but a few.

The direction of questions to the patient is totally dependent on the presenting complaint. Hence, when we consider ACS, we know that it causes crushing, severe chest pain with pain radiating to the neck, jaw, arms. There can be sweating, nausea, vomiting, collapse, palpitations etc. The duration of pain is usually defined as lasting more than 20 minutues.

Now, we need to translate such information into questions.

For example,
'Please tell me what the pain feels like' [open question]
'Does it feel like a heavy pressing feeling? Like an elephant sitting on your chest?' [closed question]
'Does the pain travel anywhere else?' [semi-open question]
'Does it travel to your neck, jaw or down your arm or arms?' [closed question]
'What time did the pain start? What were you doing at the time?' [open question]
'How long do you think you have had the pain?' [open question]
'On a scale of 1 to 10, 1 being almost no pain and 10 being the worst pain imaginable, where would you put this pain on that scale?' [visual analogue scale -- very important!]
'Have you had any other symptoms with this pain?' [open question]
'Have you had any nausea, vomiting, palpitations or loss of consciousness ?' [closed question]
'Have you had a pain the same as this before?' [open question]

The above example is a string of 'stock' questions for defining possible Acute Coronary Syndrome which then makes us consider the investigations and treatment even before the laying on of a stethoscope.

On the hand, the patient may say that the pain feels sharp when breathing, which takes us down the route of ALSO asking about causes of pleuritic chest pain. We still ALWAYS ask about the ACS, aortic dissection, oesophageal rupture questions as well. We DO NOT miss them out just because the pain sounds pleuritic. We go back to these other screening questions AFTER dealing with the specific questions for pleuritic chest pain.

Hence, 'Please tell me what the pain feels like' [open question] -- SHARP, WHEN I BREATH IN
'Do you have a cough or phelgm?' -- YES, I COUGHED UP SOME PHELGM
'What colour was the phelgm?' -- I AM NOT SURE.....
'Was it white, yellow, green, brown or red like blood?' -- ACTUALLY, IT WAS RED LIKE FRESH BLOOD
'Do you feel feverish or chilly?' -- NO
'Have you got any other symptoms?' -- YES, I FEEL A BIT BREATHLESS
'Can you tell me when it happened?' -- MMM, IT WAS SUDDEN, WHEN THE CHEST PAIN CAME ON
'Can you tell me how severe your breathlessness is? For example, are you breathless talking to me now or just when you walk?' -- I AM BREATHLESS WHEN I WALK
'Do you normally get breathless?' -- NO, I AM USUALLY OKAY TO WALK ANYWHERE WITHOUT A PROBLEM
'Do you feel any other symptoms?' -- SUCH AS?
'Well, do you have any palpitations of your heart? Does it feel irregular, fast or slow?' -- IT FEELS FAST AND IRREGULAR
'Have you noticed this problem in the past?' -- NO, I HAVE ALWAYS BEEN HEALTHY
'Have you been unwell recently?' -- NO
'Have you taken any recent long-haul flights?' -- YES, I FLEW TO AUSTRALIA FOR A SHORT HOLIDAY. THE FLIGHT TOOK 18 HOURS. I CAME BACK 3 DAYS AGO.
'Do you have any leg swelling? Any pain or redness of either leg?' -- YES, I NOTICED IT THIS MORNING. MY RIGHT LEG SEEMS SWOLLEN AND PAINFUL.
'Have you been diagnosed with any cancer recently? Or do you take any hormone replacements such as the contraceptive pill?' --NO
'Do any of your family have any history of blood clotting problems?' YES, MY MOTHER HAD A CLOT IN HER LEG IN THE PAST. SHE HAD TO TAKE WARFARIN FOR THE REST OF HER LIFE. THE DOCTORS DID NOT KNOW WHAT CAUSED IT IN HER DAY.

At this point, the diagnosis of deep vein thrombosis causing pulmonary embolism is pretty well established just from the history. The history also tells us that the patient has at least two risk factors -- remember Virchow's Triad? She has poor flow from a long-haul flight and a familial tendency to form clots [hence a change in blood viscosity]. Two out of 3 of Virchow's Triad predisposes to thrombosis. Again, from the history, it makes us consider the investigations and treatment even before laying on of the stethoscope.

After this history of the main problem, we still go on to ask about the other causes of pleuritic pain such as 'Do you have any history of tuberculosis?' 'Any recent history of a common cold e.g. running nose, earache, headache' -- remember Tb, typical pneumonia, viral infections etc, can cause pleural reactions and localised chest pain.

We also still ask about the diagnoses that should not be missed and hence, the previous ACS questions
'Does the pain feel like a heavy pressing feeling? Like an elephant sitting on your chest?' [closed question] -- NO
'Does the pain travel anywhere else?' [closed question] -- NO
'Does it travel to your neck, jaw or down your arm or arms?' [closed question] -- NO
'What time did the pain start? What were you doing at the time?' [open question] -- 8:30 THIS MORNING, I WAS WASHING THE DISHES.
'How long do you think you have had the pain?' [open question] -- AT LEAST 2 HOURS
'On a scale of 1 to 10, 1 being almost no pain and 10 being the worst pain imaginable, where would you put this pain on that scale?' [visual analogue scale -- very important!] -- 5/10
'Have you had any nausea, vomiting, palpitiations, loss of consciousness ?' [closed question] -- YES, PALPITATIONS ONLY BUT NONE OF THE OTHER SYMPTOMS
'Have you had a pain the same as this before?' [open question] -- NO, NEVER

Hence, the response of the above questions takes us away from ACS as the cause and keeps us pointing towards DVT-PE.

The specific questions for aortic dissection, oesophageal rupture and other pathologies still need to be asked so that they are not missed. It is best to be thorough. Sometimes, patients present with TWO pains, and both could be life threatening so it is only with the history being taken methodically that the cause of the different pains can be elucidated.

As can be appreciated, it is the presenting complaint that stems the follow-on stock questions in order to identify serious pathology so that a rapid diagnosis can be made and the correct treatment can be instituted.

From the above history, we are soon able to narrow down the diagnosis to DVT-PE by changing from open to closed specific questions. Once the critical diagnosis is considered, the physician seeks to establish the cause and risk factors for the problem. In doing so, when performing the physical examination, the physician would focus the examination on the cardiorespiratory system by looking for tachycardia, raised JVP, pleural effusions, crackles, signs of DVT in the lower limbs.

In view of the family history, the patient would be screened for familial coagulopathies, a D-Dimer would be checked and the patient would have an ECG to screen for ACS and ECG abnormalities associated with PE.
The patient would receive a chest radiograph to look for a widened mediatinum (screen for dissection), consolidation, effusions etc.
The patient would receive a spiral CT of the chest and a doppler ultrasound of the lower limbs and pelvis to look for thrombosis whilst receiving full treatment dose of heparin as soon as possible.

Hence, in summary, when we hear the chief complaint, we must immediately begin to think of diagnoses that fit the initial pattern. We must consider life threatening diagnoses first. When thinking of the pathology, consider how the disease can manifest. Then consider how those manifested problems can be explained by symptoms. Then pose those questions to the patient.

Explore all the serious pathologies before moving down the list on to the less severe and non-acute causes of the symptoms.

In the end, you will have taken a very detailed history and have many pertinent positive and negative symptoms and hopefully, a very focused history of the disease you have already considered at the very first mention of the chief symptoms. It is important though to take the history rapidly in the case of life threatening problems such as ACS. In such situations, it is often the case that the doctor takes the history whilst examining the patient :-o

At first it may be difficult to think in this way but with practice, being able to take a history will become easier in time. Remember though, read about your patients conditions and remember what they tell you. It will help you make diagnoses in your future patients too.

Please consider....

Physical Examination - Revisited ---- again

Dear Bloggers

I have been exceedingly busy recently ! However, I am back :-)

I wanted to reiterate the importance of the physical examination. One method of teaching from the UK involves taking no history from the patient and hence, using only observational skills to make a diagnosis! Although history can give the diagnosis in a high percentage of cases, the physical exam aids the physician to confirm or refute various differential diagnoses in certain circumstances e.g. the patient complains of palpitations but on the physical examination the patient has a normal pulse despite the patient still being symptomatic. On the other hand, the patient might complain of unilateral pleuritic pain, cough and sputum and the physical exam reveals a pneumonia. Hence, physical examination can be positively or negatively correlated to the history.

The purpose of performing the bedside exam without the history is to hone the skills of the residents to get them to look but also to recognise what they see. Observational skills are exceedingly important and are often under-utilised. For example, when starting the physical examination, perhaps the most important thing is to look around the bedside. Many items surround the typical patient e.g. portable toilet (maybe the patient is too weak or too breathless to walk), the walking stick, intravenous infusion (rehydration, antibiotics, other drugs), oxygen via mask or nasal specs, the patient's regular drugs! These elements give the physician an idea of the patient's general status and functional capacity. They can also reveal the patient's previous medical history and tell you what is wrong with them! For example, a recent patient had a mitral valve murmur and had an infusion of gentamicin running into a peripheral vein. The immediate diagnosis to consider was infectious endocarditis!

Looking for the urine bag can provide information about the patient's vascular state and type of illness- is there urine? Check the colour -- e.g. blood, coke coloured (glomerulonephritis), orange (liver disease / Tb drugs), purple (UTI), green (propofol, UTI). Concentrated urine of small volume suggests hypovolaemia before even touching the patient.

Looking at the patient at the end of the bed generally can give clues -- general state e.g looks well / unwell, weight loss (backs of the hands, temporal regions, upper arms and legs), colour of the skin / sclerae at a distance e.g. jaundice. Many clues about the patient can be picked up like this to make a preliminary opinion of the patient's condition before even laying a hand on the patient.

The UK way of examination, after general inspection, starts with the hands. The hands are an important part of the physical exam -- the type of handshake might indicate a neuropathy or myopathy. Unilateral wasting of the dorsal interossei might suggest a unilateral Pancoast tumour of the lung. Checking the fingers for clubbing can very quickly narrow the problem down to specific cardiac, respiratory or abdominal causes. Many other signs are present in the nails which are beyond this talk today. However, having a combination of signs may overlap with just a single condition and give the diagnosis or there may be separate diagnoses! For example, a recent patient with clubbed fingers also had Terry's nails, which when both present suggests liver disease. The patient had mild scleral jaundice and was unkempt. The resident rightly considered alcoholic liver disease, and he was correct. The liver was markedly enlarged and firm.

Checking the nail folds is imperative because infarcts may be seen in addition to capillary loops (seen with an opthalmoscope) which might indicate several forms of vasculitis or other rheumatological conditions. Of course, checking the digits may provide the diagnosis of rheumatoid arthritis or osteoarthritis. Asking the patient to extend the hands at the wrists with spreading the fingers can help identify those patients with encephalopathy e.g. liver failure, uraemia, CO2 retention.

Checking the pulse is not just counting the rate per minute. Feeling the volume is important. It may indicate the slow rise of aortic stenosis or the fast upstroke and immediate loss of the Waterhammer pulse of aortic regurgitation. A low volume 'thready' pulse may indicate poor cardiac output or hypovolaemia. The jerky pulse may even suggest HOCM at the wrist!

Checking the skin turgor can help indicate the fluid status of a patient although it is not so accurate in the elderly patient. However, a combination of signs e.g. thready pulse, tachycardia, cold digits, small volume concentrated urine in the catheter bag in addition to poor skin turgor indicate hypovolaemia. You don't need the BUN and Creatinine to tell you that. information as physical examination does just fine. The use of lab data in such a circumstance is to know the extent of the derangement :-)

Moving up to the head, the sclerae can be checked -- they might show anemia, jaundice, haemorrhages etc.. Again the mouth and throat can provide information. Checking the mucosal surfaces may reveal the Kaposi sarcoma or the lateral border of the tongue may have the Oral Hairy Leukoplakia of AIDS. The presence of white exudates on the mucosa and tongue suggest candida and then one must consider the DDx of why the patient has got it e.g. immune suppression from steroids, DM, AIDS. Has the patient been using recent antibiotics. Mucosal bleeding may be present indicating possible thrombocytopaenia!

Telangiectasia on the tongue, under the tongue and on the face with the presence of spoon nails 'koilonychia' should lead one to consider the rare diagnosis of Osler-Weber-Rendu (Hereditary Haemorrhagic Telangiectasia) with iron deficiency anaemia.

The facial skin can give a wealth of information. One might see the purply-red cheeks of SLE! However, remember that in an elderly patient with swollen legs, purple lips and purple fingers with the facial 'flush' is more likely to be due to low cardiac output e.g. CHF, rather than SLE!

Checking the neck can provide further information - the JVP being elevated and evaluating the wave form e.g. a wave or v wave, can tell use which problem may exist e.g. tricuspid regurgitation. Observing the neck for the carotid pulsation may reveal Corrigan Sign (common) and DeMusset's sign (head nodding with each pulsation -- rare). If you do see this sign or suspect aortic regurgitation then go back and look at the hands again. Try and find Quinke's Sign. I have found Quinke's sign in many patients simply because of the suspicion of AR through these ancillary signs and a suggestive murmur. Unless you look you will not find.

Checking the earlobes can reveal Frank Sign -- the diagonal earlobe crease suggestive of coronary artery disease although this depends on the population in question. The highest association is in caucasian patients.

The chest surface examination can reveal spider naevae and gynaecomastia of chronic liver disease, excoriations due to pruritis or tattoos and old scars amongst others. Looking at the skin teaches us about the patient's present and past.

Abdominal inspection may show obvious distension, eversion of the umbilicus, and caput Medussa of chronic liver disease.

The lower limbs can reveal similar features from the hands e.g. Clubbing, Terry's nails. However, specific rashes may occur which can give a clue about the illness e.g. petechial haemorrhage may suggest low platelets or a vasculitis. The presence of palpable, painful, multifocal erythematous lesions may suggest erythema nodosum with its respective differential diagnosis.

Notice, no chest or abdominal organ has been palpated, percussed and no stethoscope has been placed on the patient in the above examples of examination. All of the above signs can be found on inspection and point towards various diseases. Of course, examination of the heart, lungs and abdomen should be performed on a normal basis as well. However, what I am trying to emphasize is that physical examination is not just focusing primarily on the major organs. It is also looking at all the other areas of the body, which are often under appreciated, to try and pick up relevant clues which may relate to the problem of the major organ and thereby provide the clinical diagnosis at the bedside based on pattern recognition of disease.

Observational physical examination skills training, with a senior doctor who can then point out the relevant signs if the resident misses them, leads to improvement in recognition skills by the residents. By explaining the history to the resident after their finishing the examination, reinforces the physical signs teaching. Not only that, it is really exciting to see as things unravel.

For those medical educators out there, you may wish to consider doing this training with your residents. It can be illuminating to hear the correct diagnosis come forth without a word of history being heard and not a lab test or scanner in sight :-) Please consider....

An old disease in modern times -- be safe, not sorry.

Dear Bloggers

It is occasionally the case that a patient is admitted to hospital with because of an abnormal chest Xray showing upper lobe infiltration. History and physical examination are of prime importance because they can identify the possible causes and associated risk factors related to the abnormality.

Without taking a detailed history, you may be missing a serious diagnosis. For example, as a case vignette, an elderly lady was admitted to a hospital with worsening dyspnoea. She had a background of end-stage COPD from 80 pack-years (Brinkman 1600) of smoking.

Unfortunately, the history was incomplete (and therefore so was the subsequent assessment and plan) because the resident had failed to elicit from the patient that she had an active cough and sputum.

The chest radiograph revealed bilateral upper lobe infiltrates, a simple pneumothorax and hyperinflation consistent with COPD.

The patient was admitted for 'observation' to an open ward with other patients and was not wearing a face mask.

Examination revealed an emaciated patient with a hyper-expanded chest. She was mildly febrile (37.5 deg C), respiratory rate 24/min, HR 90 regular, BP 130/80mmHg and O2 Sats 98% on 2L oxygen via nasal cannulae. Lymph nodes were not palpable. There was increased percussion sound throughout the chest but reduced air entry in all lung fields and crackles at the left apex.
The rest of the examination was within normal limits.

In view of the high prevalence of tuberculosis in Japan, this should be the very first consideration in any patient with upper lobe infiltrations with pneumothorax. Although COPD is the commonest cause of pneumonthorax (70%), the concommittant existence of both radiographic features point primarily towards Tb. At the bedside, more history was taken and it was revealed that the patient did indeed have a cough and sputum. In fact, she coughed up sputum right in front of the medical team.

There are several other causes of upper lobe infiltrates defined by the following mneumonic:

S - Sarcoidosis, Sulfa drugs, Silicosis
H - Histoplasmosis
I - Idiopathic
R - Radiation induced
T - Tuberculosis (post-primary)

C - Chronic allergic alveolitis
A - Ankylosing spondylitis, Aspiration penumonia
P - PJP (when using pentamidine nebulisation), Progressive Massive Fibrosis
E - Eosinophilic granuloma

On closer inspection of the chest radiograph, the patient had vertebral body changes with calcified ligaments that might be consistent with ankylosing spondylitis. However, sometimes, severe facet joint osteoarthritis can present in this manner in the elderly as can Diffuse Idiopathic Skeletal Hyperostosis. Ankylosing spondylitis usually presents in a younger age group and is relatively rare. Osteoarthritis is very common and a more likely explanation for the 'bamboo spine' changes.

However, given the above scenario, what is the likely cause for bilateral upper lobe infiltration in a patient with COPD?

Of course, atypical presentation of a community acquired pneumonia is possible. e.g. Streptoccous pneumoniae. Moreover, Klebsiella pneumonia, H. influenza, Pseudomonas or even post-influenzal staphylococcal infection can present in such a way. Atypical pneumonia should also be considered. Of course, this patient might have aspiration but bilateral infiltration with the absence of lower lobe infiltration would make this diagnosis somewhat tenuous.

However, the above infections can be diagnosed rapidly and treated quickly and effectively with standard antimicrobial agents. Tuberculosis on the otherhand is difficult to diagnose and requires multiple antibiotics for many months. Moreover, Tb is very infectious and has an infectivity rate of about 10% ! That translates to 1 in 10 persons becoming infected and developing active disease at some point during their life from a patient coughing up active Tb into a space where the Tubercle bacilli remain airborne.

Hence, anyone with even the remotest suspicion of active tuberculosis who is coughing up sputum must not be placed on an open ward. They must be admitted directly to an isolation room with negative pressure (air is sucked into the room). Full protective garments should be worn by the medical staff including the 3M filtration face masks.

Such patients should be kept isolated until such time that tuberculosis has been excluded. Please see any good infectious disease book for the work-up of tuberculosis e.g. Dr Makoto Aoki's Infectious disease book.

It is no good trying to make an simple diagnosis e.g. aspiration pneumonia, without first excluding the serious/life threatening diagnoses that one 'should not miss'.

As I have heard many times in Japan 'In any patient with a fever, always consider tuberculosis'. I think that is a very apt saying and which I fully support.

Further widely quoted advice is 'rule out Tb before starting the steroids'. Again this is very important. Corticosteroids can reactivate latent Tb or worsen existing Tb. So be careful to check the PPD skin test, sputum examination and culture before pulsing your suspected interstitial pneumonia patient with methylprednisolone which might actually be Tb.

Usually, interstitial pneumonia patients can afford to wait for several days before starting the steroids giving enough time for the preliminary Tb examinations to be done. However, if steroid therapy is necessary because of worsening disease or for example, the patient has an 'infective exacerbation of COPD' requiring steroids with a suspicious CXR suggesting Tb, anti-Tb therapy should be commenced with the steroids (preferably after Tb samples have been taken) in order to treat this suspected infection along with that of the the acute illness. If Tb is later ruled out by tests, the Tb therapy can be stopped. It is better to be safe than sorry.

This is supported by UpToDate 17.1 in the section under Major Side Effects of Systemic Glucocorticoids which says 'Conventional wisdom suggests that any patient with a positive PPD skin test, a suggestive chest radiograph, or a strong family history of tuberculosis should receive antituberculosis prophylaxis prior to, or concomitantly with, glucocorticoid therapy'.

You cannot take the risk of having a single patient on an open ward with active Tb. Yes, it may cause the nursing staff / doctors / managers some extra work in order to organise an isolation room, but by not doing so puts many people at risk of Tb exposure.

Please consider....

Answer To Recent Case

Dear Bloggers

I hope the picture quiz gave you something to ponder over. So, what is the answer?

Here are some recent answers to the blog case:

1) Maybe the electrode on the upper right should be placed more on the sternum to prevent artifacts on the ECG. I can't find any other problem. Can't wait to hear the answer!

SL, Japanese Medical Student.

2) I can see the mark of AED. He might have been soaked at that time. I have no idea otherwise, so I'll wait for the answer.

Dr K, 1st Year Japanese Resident

Now look carefully. The patient is obese and intubated. There is evidence of defibrillator paddle / pad application on the skin of the upper left abdomen and right upper chest. The fact that two doctors are listening for bowel sounds suggests that the patient survived the resuscitation otherwise they would be listening for heart and lung sounds!

So what is the problem here?

The problem is the prior position of the defibrillator paddles. Although the patient no longer has the paddles in place, it can clearly be seen where they were placed and it clearly shows the paddles were placed incorrectly.

The lower apical paddle should have been placed craniocaudally and just left to the nipple with the centre of the electrode in the mid-axillary line.

As can be seen, this patient's spleen was targeted instead :-)

The right upper para-sternal pad has clearly been placed in a horizontal position rather than the suggested vertical position.

The European Resuscitation Council guidelines describe how the pads/paddles should be positioned as follows "The right (sternal) electrode is placed to the right of the sternum, below the clavicle. The apical paddle is placed in the midaxillary line, approximately level with the V6 ECG electrode or female breast. This position should be clear of any breast tissue. It is important that this electrode is placed sufficiently laterally"

The ERC posters also show how the pads should be placed


Now compare to the resuscitated patient below:


Inappropriate placement of defribillator paddles causes non-cardiac tissue to be defibrillated rather than the heart and makes the process of advanced resuscitation less efficient. Despite asystole being the initial rhythm in this patient on arrival of the emergency medical services, upon CPR it changed to pulseless VT then requiring multiple defibrillations. The effective resuscitation of the medical team (hands in view) resulted in restoration of sinus rhythm, and a cardiac output not requiring any initial catecholamine support!

Having defibrillated many patients over the years from in-hospital and out-of-hospital cardiac arrests, it is clear to me that pad placement is important. However, the use of the old-style paddles rather than the newer stick-on pads is less efficient for delivery of the electrical charge. Moreover, biphasic defibrillators have become more popular over recent years and the old monophasic versions are being 'phased out'. Nonetheless, if the pads/paddles are placed wrongly, you are just as well wasting the electricity, as charge is directed away from the heart muscle.

This is not just my opinion. The ERC guidelines provide clear guidance on pad /paddle placement. Moreover, a small but well known single-centre study was performed 7 years ago whereby seniors and junior doctors were asked to place electrodes on a manikin in a simulated situation of a cardiac arrest. Very few of just over 100 doctors were able to place both pads in the correct position. Both senior and junior doctors made equal errors in pad placement! The link to this BMJ study is here.

This simple study showed how important it is to have correct pad/paddle placement. This study also reminded me of the importance for regular cardiopulmonary resuscitation training. It is currently done on an annual basis in UK hospitals for all doctors. Those that fail the test (both oral and/or practical) have to practise and repeat the test until they pass!

So next time you are involved in a resuscitation event when defibrillation is being performed, please try to apply the correct pad/paddle placement. If you are using stick-on pads, please LOOK and see if they are in the correct position. Most modern pads actually have right and left printed on the surface with diagrams of how to apply the pads.

If not correctly applied, when the cardiac massage component of the protocol is underway, move the pads to the correct position. However, one word of warning, please ensure that the patient's chest has previously been shaved and all air is excluded from beneath the pad and when it is stuck down otherwise the patient can receive a nasty burn!

Correct paddle placement should be ensured by the doctor carrying out the action. Firm pressure must be applied to each paddle so that the complete defibrillating area of the paddle is apposed to the chest wall. If possible, try and use the 3M gel pads instead of the old-style gel and replace them every 3-4 defibrillations.

Also, remember, for all those doctors who wear a neck tie to work, tuck it into you shirt so that you don't get defibrillated along with the patient when you shout those famous words 'STAND BACK!'

Please consider :-)

What is wrong here? A Clinical Spot Test

Dear Bloggers

Welcome to spring! Here is a photo of the beautiful Cherry Blossom in full bloom. I hope it fills you with the same joy as it did me.


However, on a more serious note, please take a look at the photo below. It shows the torso of a Caucasian patient following an out-of-hospital cardiac arrest. (This photo was sent to me anonymised)
Please look at the picture carefully. Can you tell what is wrong here? Please send me your answers and see if you are right.
All contributions will be published with the final answer to this spot test.




Good Luck!

The Dangers of Over-Reliance on Radiology than Patients Symptoms and Signs

Dear Bloggers

Sorry I have not been writing recently. I have been so busy, it has been difficult to collect my thoughts to put down online for you.

What I would like to discuss today, is the danger of relying on radiology rather than patient's symptoms and signs. Over time, I have heard of several cases, particularly involving the elderly, who have been admitted to various hospitals with pain or non-specific symptoms. The history and physical exams may not have been taken in detail and the patient then undergoes selected lab tests and radiological investigations which are deemed 'normal'. In view of the disparity of symptoms to scans, the patients have on occasion, been sent home.

In one of these anonymised cases a patient had severe abdominal pain of acute onset. The physical examination revealed some non-specific abdominal tenderness but no rebound or guarding with normal bowel sounds. A rectal examination was not performed but instead an abdominal Xray was done which showed loading of the colon with stool. The patient was reassured that the symptoms were purely related to constipation and he was sent home. However, the patient's pain was unrelenting and he re-presented to the hospital. After further workup, a contrast CT was performed which revealed splenic infarction.

A further anonymised case was of a female with lower back pain who had developed fever. She presented to a local hospital. The patient's pain was severe but was non-specific except its location was in the lower back. Movement made the pain worse. Straight leg raising had not been performed but application of pressure over the spine did not worsen the pain. Plain radiographs were taken but no abnormalities were seen. Urine examination was normal. The patient was considered to have non-specific musculoskeletal pain and was discharged home. This patient re-presented to the hospital and a further workup was instigated.

Blood cultures grew streptococcus spp in four culture bottles. Echocardiogram (trans-thoracic) was normal. CT and MRI scans of the back were normal.

However, the scans were repeated after several days which then revealed osteomyelitis. Thankfully, the patient had already been commenced on appropriate antibiotic therapy.

In all the above cases, the patients were seen by physicians who lacked experience and who relied on lab data and radiology to make their decisions. The histories in both cases involved severe pain but such symptoms were seemingly not appreciated.

Pain is not something that should be accepted as normal in the elderly. Pain should always be taken seriously as it is the patient telling us that there IS a problem which therefore, needs to be fully investigated.

Acute onset of pain is far more relevant diagnostically than chronic pain that waxes and wanes. It is a serious warning sign. For example, fever and lower back pain should immediately make the physician think of the serious causes of these symptoms that should not be missed, which include:

• Osteomyelitis
• Discitis
• Psoas abscess (sometimes bilateral)
• Multiple myeloma
• Paravertebral abscess
• Pyelonephritis (sometimes bilateral)

These causes must be excluded before even considering sending a patient home.

In these two cases, the symptoms of pain were severe but the causes of which were not supported by basic radiology. Just because basic radiology looks normal does not mean that there is not a serious problem. It does not mean that we can safely discharge a patient. Quite the contrary. Elderly patients are sometimes difficult to diagnose and have a lower threshold for admission to hospital and especially as they can deteriorate rapidly.

Moreover, the pain itself needs to be addressed and not considered as inconsequential. It is very important. Doctors need to adopt a more holistic and humanitarian approach to patients rather than just considering the pathophysiological causes. The latter is academic but forgets that this is happening to a patient - a human being. Patients should receive analgesia as soon as possible on entry to a hospital for severe pain e.g. morphine in AMI, and should never be kept in pain for fear that the symptoms might resolve and therefore make the condition undiagnosable. The approach of withholding pain relief is not relevant to modern practise and is inhumane to patients.

Please do not think that the use of opiate medication for severe pain in the acute situation is going to lead to addiction. Chronic use can lead to addiction but again, that should not be a primary reason for not using it - pain control should be the ultimate goal. Patients with end-stage disease e.g. disseminated cancer often benefit from good pain relief. It does not mean they will become 'addicts'.

In these anecdotal 'grey cases' the patients need to be hospitalised without equivocation. They need adequate pain relief. Believe what they tell you. They are telling you the diagnosis. Even if the basic radiology is normal, take more history to try and elucidate the cause. Re-examine. Ask your senior physician to review the patient for a second opinion. Perform the advanced radiology e.g. CT or MRI. Get an experienced doctor to review the scans or even better, a radiologist.
Don't send the patient home if the diagnosis is unclear. Certain disorders e.g. abscess formation, takes time to fully manifest and an initial scan can be normal.
Believe in the patients symptoms and signs. Don't be fooled by a normal scan. Scans can change over time and reveal that the patient has been telling you the truth all of the time.

Bearing that in mind, many of you are probably thinking 'But if I admit every patient I see (because I have no idea of the diagnosis) then my boss is going to get really angry with me for all the extra work I have created'. Don't worry about your angry boss. Worry about the patients; they come first. It is better to have patients in hospital under investigations and treatment for potentially severe problems rather than inappropriately labelling them with constipation or simple back pain and sending them home. That does not help the patient, and also causes detriment to you too.

Moreover, believe in yourself and your learned skills. When I was a junior doctor, only 3 months out of medical school, a patient with decompensated liver disease developed a fever and back pain over night. The patient was septic with a high fever, tachycardia and low blood pressure. His lower back was tender to palpation although not over the costovertebral angles (loin region). Urine examination revealed evidence of infection. I suspected a UTI with secondary haematogenous osteomyelitis / discitis.

On the morning ward round, my boss (a most distinguished doctor in a high level university hospital) listened to the night's events and said that I must be mistaken - it was just a UTI. However, despite several days of intravenous cefuroxime (2nd generation cepahalosporin) the sepsis did not abate and the back pain worsened.

Another doctor on the team also considered that ruling out a more serious cause was warranted and so a CT scan was arranged - it confirmed the discitis.

Take Home Message

• If you don't know what is going on with a patient who is experiencing severe pain and / or non-specific symptoms that make diagnosis difficult (and it is of concern to you as a doctor, the patient or the family) please do not send the patient home expeditiously.
• It is better to keep the patient in hospital for observation and further studies
• Avoid Ageism
  
• Be humane and treat pain. Your patients will appreciate you very much.
• Remember, that diseases take time to manifest. Repeat history taking, physical examination and advanced scans can reveal the diagnosis in the end.
• Always inform your senior doctor if you have a difficult to manage patient. Their experience of similar cases can provide a wealth of knowledge on how to make the diagnosis and manage the patient safely and effectively.
• The time honoured adage of 'All things reveal themselves in time' is perhaps a fitting comment for such patients. However, you must be certain to exclude serious pathology quickly but also appropriately consider those disorders that may take time to manifest. Hence, in this latter idea, taking the 'wait and see' approach is far better than the 'bye bye' approach.
• Believe in yourself and your skills.
  

Please consider.....

Answer to the March Case

Dear Bloggers

I hope you have had a good think about this case. It is difficult. I had no responses this month. To be honest, I am not surprised. Many very good physicians saw this patient and were unable to explain the variety of symptoms lacking physical signs, except pain, coupled with iron deficiency and absent inflammation.

It was only when an astute physician (Dr E.) decided to revisit the patient's history and with asking specific questions, did the possibility of this condition come to mind. The patient had been misdiagnosed variously with several other problems, given ineffective and inappropriate therapies.

When one has a difficult case such as this, it is best to stand back and look from afar. Remember the common conditions and put the rare diagnosis last, not first :-)

Now, let's get down to the nitty gritties of the case!

Question 1: Please make a full problem list.

The full Problem List is as follows:

* Headache - requiring rest in a dark room
* Dizziness - present when prostrate and worse on standing
* Fatigue
* Myalgia - diffusely distributed
* Non-specific chest discomfort (likely musculoskeletal)
* Poor concentration
* Recurrent Mouth ulcers & odd eating habits
* Heavy periods
* Excessive tiredness and sleepiness
* Previous migraines
* Previous iron deficiency anemia
* Family history of gastric cancer
* Family history of dysrhythmia
* Microcytic anemia with low ferritin

Question 2: What is your differential diagnosis given the thorough history and physical examination plus basic tests?

In this case, one needs to consider the common and then the less common differential diagnoses. As this patient is below the age of 50, we can consider the possibility of one single condition causing all the problems (Ockham's Razor) although we should still bear in mind Hickham's dictum i.e. the patient is allowed as many diagnoses as she likes.

Let us examine each main problem in turn.

Headache - this is a non-specific feature. The only clue to its potential origin is the fact that the patient wants to sleep in a dark room which is consistent with migraine. However, the pain is different from her previous migraines. This does not exclude migraine as the disorder can present in different ways over time. There are no associated auras of note. Again, this does not exclude migraine. Tension headaches should also be considered.

Waking with headache can be a feature of migraine although it makes one consider the problem of raised intracranial pressure. However, other features such as vomiting, visual disturbance are missing and moreover, the history is chronic rather than acute. One diagnosis in young women associated with headache and intracranial pressure is benign intracranial hypertension (pseudotumour cerebri). However, such a feature is not usually associated with the other manifestations noted by the patient.

We know this patient has a history of iron deficiency anaemia. Anaemia itself can cause headache as a non-specific feature, as is the case with many other symptoms in anaemia being non-specific.

The neurological examination is normal which gives us some confidence that a massive intracranial lesion is not present. Despite this, an intracerebral space occupying lesion (SOL) cannot be fully excluded by the physical examination. However, in view of the chronicity, lack of symptom change and the intermittency of the pain and lack of other CNS symptoms makes this diagnosis in an otherwise healthy young female less likely but not impossible.

Dizziness - this is an extremely common symptom. There are many causes. This patient has undergone the usual tests for investigating causes of the dizziness. Postural hypotension does not appear to be a feature here. Cardiac examination is unrevealing although from her family history, the mother has a dysrhythmia and hence, an inherited dysrhythmia cannot be excluded e.g. long QT syndrome, WPW etc. However, common things being common, anaemia itself can cause dizziness, as can migraines, HEENT problems, etc... One feature which is quite unusual is the feeling of dizziness when motionless. This brings one to consider migrainous vertigo which can occur when motionless (and which fits very nicely!) or whether there is a non-organic cause for the symptom such as anxiety or depression. One should always exclude organic causes first before labeling the patient with a potential psychiatric condition.

Mouth ulcers and odd eating habits - together suggest iron deficiency anaemia. Odd eating habits suggest the diagnosis of Pica. The iron deficiency is very likely to be due to menorrhagia (heavy menstrual bleeding) rather than a GI cause or poor nutrition. Despite the history of gastric cancer, this patient's recent gastroscopy and colonoscopy were entirely normal.

Other causes of ulceration in mouth include: Infection e.g. HSV, syphilis (usually painless); Trauma; Haematologic e.g. Iron Deficiency Anaemia, Connective Tissue Disease e.g. UC, Crohn's, Behcet's disease; Neoplasia e.g. SCC, etc.... However, almost none of these fit with the pica symptomatology making iron deficiency most likely.

The chronic non-specific symptoms of excessive tiredness and sleepiness, poor concentration, myalgia, headaches etc suggest a multitude of different problems which include:

Infection

• Bacterial: Lyme disease
• Viral: Post-viral syndrome, HTLV, HIV

Endocrine:

• Hypothyroidism (sometimes hyperthyroidism too!)
• Hypoadrenalism
• Reactive hypoglycaemia
• Hyperparathyroidism
• Cushing's syndrome

Connective Tissue Disease / Rheumatologic

• SLE
• Polymyositis
• Mixed Connective Tissue Disease
• Fibromyaglia
• Behcet's disease
• Sjogren's disease
• Rheumatoid arthritis

Neoplastic

• Leukaemia (unlikely as would have hopefully been identified on routine lab tests)
• Lymphoma
• Endometrial cancer with paraneoplastic syndrome
• Insulinoma, pancreatic hyperplasia
• Oncogenic osteomalacia

Metabolic / Toxic

• Electrolyte disturbance (hyponatraemia, hypercalcemia etc; unlikely as these would have hopefully been identified on routine lab tests)
• Lead poisoning (iron deficiency, headaches, poor concentration,
• Chronic alcoholism ('closet alcoholic')

Psychiatric

• Depression
• Psychosomatic disorder
• Munchhausen syndrome
• Psychosis

Question 3: What additional test are required?

Common things are common. The history is extremely important here and should guide you in your lab testing. Try and avoid expensive tests that offer little extra information especially if the differential diagnoses you want to rule out are rare. Spending lots of money when you expect the test to come back negative is not the right way to do tests. This wastes time and money. It is better to test for the common things and if another disorder is still considered to be present after these initial results, then you can consider other tests at that point. Try and get out of the habit of ordering 'Panels' of expensive tests. Do not over test patients for the sake of doing tests. Rare diseases are rare.

I would test for thyroid and autoimmune disease initially. Without a history of travel within forested areas, testing for Lyme disease would not be on my initial list of tests. In view that the patient is sexually active, syphilis serology would be reasonable. An HIV test would be reasonable with patient consent. HTLV testing can be considered although it should be done depending on where the patient lives e.g. Southern Japan, Southeastern USA, would be risk areas.

Other routine tests such as Na, Ca etc would reveal deviations from normal. Raised gamma GT, AST, ALT, MCV etc might suggest alcohol albeit non-specifically.

A repeat gynaecological examination with transvaginal ultrasonography and endometrial biopsy would be reasonable to investigate and exclude malignancy.

ECG should be done to ensure there is no underlying dysrhythmia.

I would not routinely perform a CT head scan in this kind of patient. However, this is commonly done in some countries e.g. USA, Japan. Most patients presenting to their GP or hospital doctor in the UK would have a thorough history taken and a physical examination performed including fundoscopy. Unusual features of the above would be indicators for taking a head CT scan but otherwise the patient would be reassured and treated according to the likely cause. Urgent CT scanning should be reserved for patient with altered mental status, focal signs, and for any acute onset headache especially if associated with nausea and / or vomiting.

Question 4: What is your leading diagnosis?

The clue in this history is the non-specific tenderness in various sites throughout the patient's body. These locations fit for tendon insertion points. Hence, the likely diagnosis based on the diffuse mylagia, 'musculoskeletal-sounding' chest pain, poor concentration, tiredness, excessive sleepiness, headaches, dizziness etc are likely to be due to fibromyalgia!

I say this, rather than anaemia, because the anaemia resolved with iron sulfate giving a very reasonable haemoglobin level. Although this led to resolution of the anaemia, pica and mouth ulcers, it did not resolve other features suggesting that another condition was hiding beneath the surface. Hence, the iron deficiency although contributing to several non-specific symptoms was likely to be the 'red herring' hiding the true entity of fibromyalgia.

Follow-up results for this patient included the following:

• Thyroid function was normal.
  
• Autoimmune serology was within normal limits.
• HIV and syphilis serology were negative.
• Uterine ultrasonography was normal and endometrial histology was unrevealing.
• Blood sugars were normal showing no extremes of high or low.
• Blood smear showed no basophilic stippling. A formal lead level was never performed as it was thought unlikely that Pb-poisoning could have caused all these features.
• ECG was normal.

Fibromyaglia

This is a diagnosis of exclusion. However, once other more sinister diagnoses have been ruled out, the diagnosis should be entertained. It is common! Some 3-10% of the general population are said to have the condition. Fibromyalgia and chronic fatigue syndrome have much overlap. Fibromyalgia generally affects women six times more than men occurring between the ages of 20-50 years with physical examination and laboratory findings being normal. The cause is not currently known although potential contributors include viral infections, depression, sleep disorder and aberrant perception of pain have been proposed.

Patients generally complain of chronic aching pains involving the entire body with most pain focused on areas including the lower back, upper and lower limb girdle regions. Other symptoms described in this condition include fatigue, sleep disorders, chronic migraine-type headaches, numbness, dizziness, dysmenorrhoea, and irritable bowel syndrome. In fact, exercise makes the symptoms worse resulting in worsening fatigue.

Examination is normal except for pain in specific locations known as 'trigger points' as shown below:

In order to satisfy the criteria for fibromyalgia, 11 tender trigger points must be present out of the total of 18.

A summary of the problems found in the condition is below:



Question 5: What is your treatment plan?

Treatment for fibromyalgia includes

• Patient education - patients need to be informed that they do not have a serious medical condition and which is not progressive.
• Drug Therapy: Antidepressant therapy has modest benefit e.g. fluoxetine (SSRI), amitryptilline (tricyclic agent). Less than half of all patient experience benefit from such therapy suggesting that not all cases involve depressive illness.
• Exercise: Rather than resting up and taking it easy, patients should be encouraged to gradually increase their exercise tolerance by joining an exercise programme. In the UK, such exercise programmes can be prescribed on the NHS and are free for patients.

Ineffective treatments include NSAIDs, opioids, corticosteroids and acupuncture.

Fibromyalgia can take several years to be diagnosed. It may be misdiagnosed under the guise of several other conditions and hence, treated inappropriately. However, please try and keep this diagnosis in the back of your mind. Ultimately, it is the history and lack of physical signs that directs the physician to consider the diagnosis.

For further information please see any well respected evidence based text such as Harrison's, UpToDate etc...

Fibromyalgia is underdiagnosed and not well known about within the medical community. Please read the following from a Japanese patient who was diagnosed with it. It makes chilling reading - link.

A link to the Japan Fibromyalgia Support Association is here.