Vertigo: is it caused by peripheral lesions or the brain stem?

A patient is feeling unsteady or dizzy. She has difficulty in describing what she feels exactly: the room feels as if it is spinning or she is spinning while the room stands still. This is obviously illusory. She finds it difficult to maintain her balance as she has difficulty in judging the vertical dimensions of her surroundings or sometimes the horizontal dimensions. She feels unsteady and needs to hold onto a chair or table or feels that her head is spinning or that her eyes will not focus properly. In the subcontinent the word most often used to describe this feeling is “chakar” or sensation of spinning.

What is causing her to have any or all of these symptoms?

The commonest reason for vertigo is related to inflammatory lesions of the middle ear i.e. vestibular neuronitis. The common cold if severe can cause vertigo and the onset of migraine can be a cause. Travel sickness is a common cause and is usually accompanied by nausea and vomiting. Postural stability can be affected in patients with vertigo. The vestibular nuclei send signals to the vestibulospinal tract, which in turn stimulates anti-gravity muscles that maintain posture. When symptoms are less pronounced, particularly when there is pronounced nystagmus out of proportion to the severity of vertigo, think of a brainstem rather than a peripheral lesion.

Some patients may have an illusion that their body is upside down or tilted to one side. This tilt illusion, in which patients feel that they and their environment are tilted with respect to gravity, usually reflects damage to otolithic organs (utricle and saccule) or their central connections. Otolith dysfunction may also cause lateropulsion or the tendency to fall to the side of the lesion. A sudden drop to the ground without warning can occur and is called the drop attack. Drop attacks can be caused by epileptic seizures specially in older patients, or cardiogenic syncope or have a vestibular pathology.

Oscillopsia, a visual illusion of to-and-fro environmental motion and blurred vision whenever the head is in motion, is a manifestation of an impaired vestibuloocular reflex (VOR).

Impaired balance without vertigo — This is a common manifestation of acute simultaneous bilateral vestibular loss such as that occurring with aminoglycoside antibiotic toxicity. Vertigo does not occur because there is no marked vestibular asymmetry. Most patients have oscillopsia during passive head movement, as when walking or riding in a car over rough terrain. Imbalance is most marked in the dark when visual cues to position in space are not available.

How are you going to set about determining why your patient is having problems with their balancing apparatus? Take a detailed history specially of associated symptoms current or in the recent past specially related to ear, nose and throat. Ask about drugs used medicinally and for leisure. Ask about associated conditions such as diabetes, hypertension, epilepsy, past history of stroke or ischemic heart disease. Inquire about aggravating and provoking factors.

Examine the patient for nystagmus, eye movements, balance and gait. Do the DixHallpike and HINT tests, check the cranial nerves, motor and sensory systems, check the hearing clinically.

Keep in mind that vertigo comes and goes and is not a permanent symptom, Association with nystagmus and persistence of vertigo tends to occur in in stroke and brain stem lesions.

Acute onset, sustained vertigo: common diagnoses in this setting include vestibular neuritis, demyelinating disease, and a stroke in the brainstem or cerebellum.

Very brief episodes of isolated vertigo that are precipitated by predictable movements or positions of the head are often caused by benign paroxysmal peripheral vertigo (BPPV).

The Dix-Hallpike maneuver can help confirm this diagnosis. With the patient sitting, the neck is extended and turned to one side. The patient is then placed supine rapidly, so that the head hangs over the edge of the bed. The patient is kept in this position until 30 seconds have passed if no nystagmus occurs. The patient is then returned to upright, observed for another 30 seconds for nystagmus, and the maneuver is repeated with the head turned to the other side. The latency, transience, and fatigability, coupled with the typical mixed upward vertical and torsional direction, are important in diagnosing BPPV due to posterior canalithiasis.
The lack of evidence to support performance of the HINTS exam by EPs does not prove we cannot use it successfully.

Head impulse test — The head impulse test (or head thrust test) is performed by instructing the patient to keep his or her eyes on a distant target while wearing his or her usual prescription eyeglasses. The head is then turned quickly and unpredictably by the examiner, approximately 15°; the starting position should be approximately 10° from straight ahead.

The normal response is that the eyes remain on the target (figure 3). The abnormal response is that the eyes are dragged off of the target by the head turn (in one direction), followed by a saccade back to the target after the head turn; this response indicates a deficient VOR on the side of the head turn, implying a peripheral vestibular lesion (inner ear or vestibular nerve) on that side

The HINTS (Head Impulse, Nystagmus, Test of Skew) exam has been shown to accurately identify central causes of vertigo when performed by neuro-ophthalmologists on patients with acute vestibular syndrome (Stroke 2009; 40:3504). To compare the accuracy of HINTS exams performed by emergency physicians (EPs) and neurologists for identifying central causes of vertigo, researchers performed a systematic review and meta-analysis. Inclusion criteria were adult patients with acute vestibular syndrome (constant vertigo, nystagmus, ataxia) evaluated with a HINTS exam performed by any clinician, with neuroimaging as the gold standard.
In the five studies identified, overall risk of bias was moderate. In most studies, HINTS exams were performed by neurologists or neuro-ophthalmologists, with a sensitivity of 97% and specificity of 95%. Only one study included EPs, and they were fellowship-trained in vascular neurology. That study also included neurologists, and for the EPs and neurologists combined, sensitivity was 83% and specificity was 44%.

The aim of this study was to further confirm high accuracy of the HINTS exam when performed by neurologists and neuro-ophthalmologists. It also highlights that the little available evidence suggests EPs do not perform the exam with the same sensitivity and specificity. Despite the limited evidence, I believe EPs can learn to perform the HINTS exam accurately. The most common mistake I see is performing it on patients who don’t have vestibular syndrome. If the patient doesn’t have constant vertigo with nystagmus, they don’t have vestibular syndrome, and the HINTS exam should not be used.

(April 3, 2020 Accuracy of the HINTS Exam for Vertigo in the Hands of Emergency Physicians. Benton R. Hunter, MD reviewing Ohle R et al. Acad Emerg Med 2020 Mar 13)

MRI of the brain is indicated in selected patients when the history and examination suggest either a central cause of vertigo or a vestibular schwannoma (acoustic neuroma). CT scans are significantly less sensitive for the diagnosis of cerebellar infarction and for pathologies affecting the brainstem or vestibular nerve.

Electronystagmography and video nystagmography — ENG uses electrodes to record eye movements. VNG uses video cameras to record eye movements. These techniques record and quantify both spontaneous and induced nystagmus. Most balance disorder centers and many specialists use ENG or VNG to assess vestibular function and ocular motility.

Vestibular evoked myogenic potentials — VEMPs are a new means of assessing otolith function.

Brainstem auditory evoked potentials — BAEPs have a 90 to 95 percent sensitivity for detecting acoustic neuromas but are not used routinely in the diagnostic workup.

By now you have a fairly accurate idea as to how to work up a case of vertigo. Keep in mind that vestibular neuronitis is the commonest cause but you may pick up a brainstem or cerebellar tumor or infarct in the course of your patient examination. Do not forget demyelinating diseases.

Understanding the logic of prevention in the COVID19 disease.

The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. The pathogen was traced to the Huanan Seafood Wholesale Market. The dynamics of method of transmission and and infection dynamics of disease have helped shape some of the measures taken to limit the spread of disease. Some of these seem to be working and some have caused catastrophes in different parts of the world. Some facts taken from a study “Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia” Published in the March 26, 2020 N Engl J Med 2020; 382:1199-1207 are given below.

Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9).

There was human to human transmission, respiratory droplets were involved in the transmission, physical contact with mucosal surfaces could result in transmission of the virus to hands and then could be transmitted to any surface touched by an infected person. The transmission could take place unless controlled by hand washing and antiseptic cleaning of the surfaces, for a period of 7 days. Hence a symptomatic patient needs to be isolated for 7 days or until tests are negative for the presence of the virus. Taking into account that an asymptomatic person can also transmit the disease and the incubation period is 14 days such a person needs to be isolated for 14 days. Families can be isolated in their homes or group accommodation. It would however be advisable to isolate the elderly and vulnerable separately in a room of their own. As the virus is not transmitted by food, drink and cooking utensils meals and food can be shared. If an asymptomatic patient becomes symptomatic then they need to isolate for an additional days.

Have we had similar viruses in the past? COVID 19 was rapidly shown to be caused by a novel coronavirus that is structurally related to the virus that causes severe acute respiratory syndrome (SARS). There have been two preceding instances of emergence of coronavirus disease in the past 18 years — SARS (2002 and 2003) and Middle East respiratory syndrome (MERS) (2012 to the present) — the Covid-19 outbreak has posed critical challenges for the public health, research, and medical communities. Two pandemics of influenza occured in 1957 and 1968. Spanish flu occured in 1917.

How often have we dealt with the corona virus in the past? Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2, have been responsible for the SARS epidemic in 2002 to 2004 and for the more recent coronavirus disease 2019 (Covid-19) pandemic. Why are these viruses infective and how do they differ from the influenza viruses? These viruses respectively, interface with the RAAS (rennin angiotensin aldosterone) through angiotensin-converting enzyme 2 (ACE2), an enzyme that physiologically counters RAAS activation also functions as a receptor for both SARS viruses. The interaction between the SARS viruses and ACE2 has been proposed as a potential factor in their infectivity. There are concerns about the use of RAAS inhibitors that may alter ACE2 and whether variation in ACE2 expression may be in part responsible for disease virulence in the ongoing Covid-19 pandemic. Indeed, some media sources and health systems have recently called for the discontinuation of ACE inhibitors and angiotensin-receptor blockers (ARBs), both prophylactically and in the context of suspected Covid-19. Is it possible that ACE2 may be beneficial rather than harmful in patients with lung injury?

Coexisting conditions, including hypertension, have consistently been reported to be more common among patients with Covid-19 who have had severe illness, been admitted to the intensive care unit, received mechanical ventilation, or died than among patients who have had mild illness. There are concerns that medical management of these coexisting conditions, including the use of RAAS inhibitors, may have contributed to the adverse health outcomes observed. However, these conditions appear to track closely with advancing age, which is emerging as the strongest predictor of Covid-19–related death.

ACE2 is a key counterregulatory enzyme that degrades angiotensin II to angiotensin-(1–7), thereby attenuating its effects on vasoconstriction, sodium retention, and fibrosis. Although angiotensin II is the primary substrate of ACE2, that enzyme also cleaves angiotensin I to angiotensin-(1–9) and participates in the hydrolysis of other peptides. In studies in humans, tissue samples from 15 organs have shown that ACE2 is expressed broadly, including in the heart and kidneys, as well as on the principal target cells for SARS-CoV-2, the lung and the alveolar cells. Of interest the role of ACE2 in the lungs appears to be relatively minimal under normal conditions but may be up-regulated in certain clinical states. ACE inhibitors in clinical use do not directly affect ACE2 activity.

SARS-CoV-2 appears not only to gain initial entry through ACE2 but also to subsequently down-regulate ACE2 expression such that the enzyme is unable to exert protective effects in organs. It has been postulated but unproven that unabated angiotensin II activity may be in part responsible for organ injury in Covid-19.

What can be done for a person who falls ill? First keep in mind that the mortality rate is low. Some people like the elderly, the immune compromised, those with other serious underlying diseases should be isolated, observed and cared for with greater intensity. Therapy currently consists of supportive care while a variety of investigational approaches are being explored. Among these are the antiviral medication lopinavir–ritonavir, interferon-1β, the RNA polymerase inhibitor remdesivir, chloroquine, and a variety of traditional Chinese medicine products. Symptomatic relief as needed has to be provided and ventilatory support needs to be available. It is the sudden demand for ICU and ventilatory support which has sent nations scrambling to impose mass isolation, social isolation and the tragic mass migration in India.

We are going to see more outbreaks of diseases related to poverty, malnutrition, emergence of new pathogens as in the wake of the economic disaster which is likely to follow this outbreak. The Covid-19 outbreak should serve as a stark reminder of the ongoing challenge of emerging and reemerging infectious pathogens and the need for constant surveillance, prompt diagnosis, and robust research to understand the basic biology of new organisms and our susceptibilities to them, as well as to develop effective countermeasures.

Paralysis in an adult man: quadriparesis/paraparesis.

A 23 year old laborer needs to be evaluated. He has been in bed for almost 3 months because his limbs are paralysed to the extent that he needs to be lifted up into a wheelchair and also when he needs a bath or a change of apparel. He needs a urinary catheter but can pass stool after being given an enema or a suppository. He has had no trauma to the neck, shoulder or head. The illness developed over 3-4 days without any headache or pain in the neck or fever. He became totally paralysed from below upwards and is now appearing to get better. On examination you find that all four limbs are involved, with marked hypertonia, grade 2-3 muscle weakness and 4-5 increased motor reflexes and up-going planter reflexes. There is no significant sensory loss. Because of the marked weakness ataxia is difficult to assess.

What is this condition?

In a regional neuroscience center in the United Kingdom, the most common cause of spastic paraparesis or quadriparesis among 585 patients was cervical spondylotic myelopathy (24 percent), followed by tumor (16 percent), multiple sclerosis (MS; 18 percent), and motor neuron disease (4 percent)

Is this transverse myelitis?

TM is a segmental spinal cord injury caused by acute inflammation usually idiopathic in origin which results in paraplegia, quadriplegia, or the Brown-Sequard syndrome. It is rapid in onset and upper motor neuron in origin. It usually occurs over a few segments and the sensory loss may be missed.TM can also occur in multiple sclerosis (MS) and can be the presenting demyelinating event. Neuromyelitis optica or Devic disease is a disorder related to MS. Remember to examine the fundi and give the reason for doing so. Connective tissue disorders can also cause TM such as systemic lupus erythematosus, mixed connective tissue disease, Sjögren’s syndrome, scleroderma, antiphospholipid antibody syndrome, ankylosing spondylitis, rheumatoid arthritis. 

Magnetic resonance imaging (MRI) of the involved section of the spinal cord shows gadolinium-enhancing signal abnormality, usually extending over one or more cord segments. The cord often appears swollen at these levels. Cerebrospinal fluid (CSF) is abnormal in half of patients, with elevated protein level (usually 100 to 120 mg/100 mL) and moderate lymphocytosis (usually <100/mm3). Glucose levels are normal. Oligoclonal bands are usually not present in isolated TM, and when present suggest a higher risk of subsequent MS

The granulomatous inflammation of sarcoidosis can affect the spinal cord and produce an acute or subacute segmental myelopathy. The lesions can be extramedullary or intramedullary, and can involve the cauda equina as well as the cord. MRI signal abnormalities are not specific; neurosarcoid lesions can appear similar to TM or can resemble a tumor. CSF evaluation usually shows elevated protein and/or pleocytosis. Hilar lymphadenopathy may suggest the diagnosis; however, serum and CSF angiotensin converting enzyme levels are neither sensitive nor specific for neurosarcoidosis. Patients with neurologic sarcoidosis are generally treated with corticosteroids and other immunomodulatory agents and can improve.

Paraneoplastic syndromes. Four of these occur are likely to be seen but are unlikely to be present in this patient. These are given below:

  • Motor neuron syndrome – a subacute, progressive, painless, and often asymmetric lower motor neuron weakness, most often associated with lymphoma
  • Acute necrotizing myelopathy – a rapidly ascending syndrome of sensory deficits, sphincter dysfunction, and flaccid or spastic paraplegia or quadriplegia
  • Subacute sensory neuronopathy – an inflammatory disorder affecting the dorsal root ganglia, producing progressive loss of sensory modalities, leading to prominent ataxia. This is most often associated with small cell lung cancer and anti-Hu antibodies.
  • Encephalomyelitis – a diffuse involvement of brain and spinal cord regions, in which cerebral manifestations frequently overshadow the myelopathy. Several syndromes are described.

Is it an acute infection?

Tuberculosis — Tuberculosis can produce a myelopathy by different mechanisms. Infection of the vertebral body leads to tuberculous spondylitis or Pott’s disease, which can lead to secondary cord compression. These patients present with back pain over the affected vertebra, low-grade fever, and weight loss, followed by a secondary compressive myelopathy. Tuberculomas within the intramedullary, intradural, and extradural space can also produce myelopathy.

Think of an acute epidural abscess specially one caused by Staph. It is a reversible cause of the paralysis. The infection can originate via contiguous spread from infections of skin and soft tissues or as a complication of spinal surgery and other invasive procedures, including indwelling epidural catheters. Other cases of epidural abscess arise from a remote site via the bloodstream. Diabetes, alcoholism, and human immunodeficiency virus (HIV) infection are risk factors.

Acute viral myelitis — Two distinct syndromes of spinal cord involvement are associated with acute viral disease. In the first, the virus targets the gray matter of the spinal cord, producing acute lower motor neuron disease. These viruses include:

●Enteroviruses, such as poliovirus, coxsackie virus, and enterovirus 71.

●Flaviviruses, such as West Nile virus and Japanese encephalitis virus.

AIDS myelopathy — HIV infection produces a vacuolar myelopathy, which is found in up to half of patients with AIDS at autopsy. However, clinical manifestations occur when the pathology is advanced, and only approximately one-fourth of patients demonstrating vacuolar myelopathy at autopsy have symptoms during life.

HTLV-I myelopathy — Human T-lymphotropic virus type I (HTLV-I) causes a progressive neurologic disease, which is called either HTLV-1-associated myelopathy (HAM) or tropical spastic paraparesis (TSP) [57,58]. This disorder is endemic in southern Japan, the Caribbean, South America, the Melanesian islands, Papua New Guinea, the Middle East, and central and southern Africa, with sero prevalence as high as 30 percent in southern Japan.

Spinal cord infarction is most frequently caused by surgical procedures and pathologies affecting the aorta but can also occur in the setting of severe systemic hypotension or cardiac arrest. Symptoms are consistent with the functional loss within the anterior spinal artery territory and include paralysis, loss of bladder function, and loss of pain and temperature sensation below the level of the lesion. Position and vibratory sensation are spared. The onset of symptoms is sudden and is frequently associated with back pain. Magnetic resonance imaging (MRI) will demonstrate a T2 signal change consistent with cord ischemia, but may be normal in the first 24 hours.

Think also of spinal a-v malformations and hematomas.

Subacute combined degeneration — Deficiency in vitamin B12 (cobalamin) leads to degeneration of the dorsal and lateral white matter of the spinal cord, producing a slowly progressive weakness, sensory ataxia, and paresthesias, and ultimately spasticity, paraplegia, and incontinence. Not all patients with neurologic abnormalities will have anemia or macrocytosis. Supplemental treatment with vitamin B12 can stop progression and will produce neurologic improvement in most patients.

Two causes of spinal cord degeneration are linked to food and are found in times of famine. Neurolathyrism is associated with prolonged consumption of the grass or chickling pea (Lathyrus sativus). Exposed persons develop a slowly developing spastic paraparesis with cramps, paresthesias, and numbness, accompanied by bladder symptoms and impotence. Konzo, a disorder characterized by acute spastic paraparesis or quadriparesis, is linked to high exposure to cyanogenic compounds in diets containing insufficiently processed bitter cassava (Manihot esculenta).

Both benign and malignant tumors can produce a myelopathy as a result of external compression or intramedullary growth.

Neoplasm. The most common syndrome is that of extradural spinal cord compression, as produced by metastases to the extradural space. Patients present with a progressive weakness below the level of the lesion with accompanying sensory loss and bladder dysfunction. Diagnostic evaluation (with gadolinium-enhanced spinal magnetic resonance imaging [MRI]) must proceed promptly when this diagnosis is considered. Intramedullary spinal cord tumors are typically primary central nervous system tumors (ependymoma, astrocytoma); metastases are less likely. These produce a progressive myelopathy, often with central cord features. MRI with gadolinium will show the tumor. Myelopathy can also occur as a complication of radiation therapy.

Is this Friedreich’s ataxia?

The neuropathologic changes in Friedreich ataxia include degeneration of the posterior columns and the spinocerebellar tracts of the spinal cord and loss of the larger sensory cells of the dorsal root ganglia. These findings correspond to the clinical manifestations of progressive ataxia of all four limbs and gait, weakness, absent reflexes with extensor plantar responses, loss of position and vibration sense, and sparing of pain and temperature. Cardiomyopathy and diabetes mellitus are part of the syndrome. Patients with late-onset disease are more likely to have retained reflexes, spasticity, and no cardiomyopathy. MRI may show atrophy of the cervical cord. Disease severity and rate of progression are highly variable. This condition is unlikely in this patient as he came in with muscle weakness not ataxia, he has no dysphasia, dysphagia, loss of sense of position and vibration. His reflexes are exaggerated and muscle tone increased. In Friedreich’s ataxia in very late onset cases there may rarely be spasticity. Check out genetic evidence of frataxin repeats (GAA), frataxin level, vitamin E level in serum (should be normal) and no cerebellar atrophy on the MRI of the brain. There is no cure.

This is an extensive subject. I have not touched on traumatic myelopathy but i have given you plenty of thought for reading up for an exam and answering some of the common questions likely to be asked.

Purpose of assessment: how to understand and plan your answer in an interactive session. Thyroiditis and Celiac Disease.

Part of an assessment aka clinical examination in a postgraduate setting, is a series of scenarios or clinical material which a candidate is asked to read and assess, What is the purpose of this form of assessment?

About the scenario: do you understand the information that is given you? Can you make a working diagnosis? Can you try to prove your diagnosis? Can you make the patient comfortable, recognize and treat complications and life threatening situations, can you restore normal or near normal functions, and follow up the patient’s functions? Obviously in the short time allotted you will be asked some of these questions but these are the questions you should prepare.

Sample 1. A 32 year old man from the Northern Areas of Pakistan. He had been unwell for 2 months. The 2 main problems were irregular low grade fever and pain in the front of the neck radiating to the jaw and temporal regions. His local caregiver has given him 3 courses of different antibiotics with the intention of treating a sore throat/pharyngitis but he has not improved. His fever is 101 degree F, with a regular pulse of 110/min, he has fine tremors in both hands and feels nervous and jittery. his appetite is good but he has lost 3 kg of weight. His ENT examination is unremarkable and the front of the neck is tender, and there is a firm palpable non-cystic small mass.

What will the examiner ask you?

  • What is the likely diagnosis or problem?
  • What disease is he suffering from?
  • Why have you reached this conclusion?
  • What is the relevant information in this scenario?
  • What is the organ or system involved?

All these are designed to see if you understood the information in the scenario and interpreted it intelligently. Answers given were as below;

  • Temporal arteritis. Wrong. You have been told that the pain begins in the front of the neck and then radiates. In temporal arteritis or giant cell arteritis temporal headaches are pretty severe and the tenderness is in the temporal regions. It is also known as Horton’s disease, and major manifestations on the basis of which it is diagnosed are new headaches, abrupt onset of visual disturbances, especially transient monocular visual loss, jaw claudication, unexplained fever, anemia, or other constitutional symptoms and signs. Labs will show high erythrocyte sedimentation rate (ESR) and/or high serum C-reactive protein (CRP). None of these are mentioned in the scenario.
  • Thyroiditis: subacute is the right answer. What else is tender other than the thyroid? It is painful and tender and there is fever hence it is inflamed so it is thyroiditis as the gland is inflamed, it has been there for 2 months so not acute and not yet quite chronic and the symptoms are muted too. There is no hint of jaw claudication in the scenario and no evidence of AF. Subacute thyroiditis is fundamentally a clinical diagnosis. In most patients, clinical manifestations (the presence of neck pain, often radiating upward to the jaw; marked thyroid tenderness; and a diffuse goiter) are sufficient to establish the diagnosis. Symptoms and signs of hyperthyroidism may or may not be present, but the serum TSH is usually suppressed (typically <0.1 mU/L) and free T4 and T3 concentrations elevated, particularly in the early stages of the illness.
  • You will be asked what specific tests you will do to further your diagnosis: prove absence of bacteria, blood culture, throat swab culture etc; C-reactive protein and ESR to prove ongoing active inflammation: check the thyroid status usually mild hyperthyroidism with low TSH. antithyroid antibodies will be absent, radioiodine uptake will be low. Thyroid crisis is unlikely to occur. Doppler ultrasound of the neck will show reduced thyroid blood flow.
  • How will you treat or manage this case and what is the objective of your management?The objective is to make the patient comfortable, reduce the inflammation and monitor thyroid function and restore it to normal. The disease is self limiting and will subside in a few weeks to months. No antibiotics are required, a full standard dose of aspirin is effective or ibuprofen or naproxen will relieve the pain and fever; no need to treat the tremors as they will settle by themselves. If the patient does not respond in a few days use an adequate dose of steroids.
  • Differential diagnosis: rarely, fine-needle aspiration biopsy, typically under ultrasound guidance, is necessary to distinguish infection (eg, abscess), hemorrhage, thyroid cancer, or lymphoma from subacute thyroiditis. However, considering the possibility of the presence of a thyroid abscess is important in all cases of subacute thyroiditis. Occasional patients with either chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) or Graves’ hyperthyroidism have neck pain and tenderness. However, the pain in both conditions is much less severe than in subacute thyroiditis, while thyroid dysfunction should be much more severe. In Graves’ hyperthyroidism, radioactive iodine uptake is high, not low. Painless (silent) and postpartum thyroiditis may cause similar changes in thyroid function and are associated with low radioiodine uptake, but thyroid gland or neck tenderness is not present.
  • Thyroid status usually returns to normal i.e euthyroid and therapy for hypothyroidism is not needed because symptoms, are not pronounced but if the hypothyroidism is more pronounced (TSH >10 mU/L) or associated with more than mild symptoms, the patient should be treated with 50 to 100 mcg of T4 (levothyroxine) for six to eight weeks (with a goal TSH in the normal range). The T4 should then be discontinued, and the patient reevaluated in four to six weeks to be sure that the hypothyroidism is not permanent.

When you are preparing for the exam this is the information you need about subacute thyroiditis. Organise it in your own mind. Remember that diagnosis depends on some or one salient point, this may be clinical or a lab investigation or a series of lab investigations. Understand and remember these. In the examination it is often obvious that the candidate is thinking of these points for the first time. This is fatal. Treatment consists of reducing distress, pain and discomfort. This is very important and not just an adjunct to the curative treatment. The curative or corrective treatment is an attempt to restore function. You may need to supply the missing hormone, electrolyte, vitamin or enzyme etc or if it is in excess then to block it with drugs or other therapy. You have to anticipate and recognize complications and then rehabilitate the patient.

Remember to read up these points. Finally read up research and controversies, recent advances and remember the name of a current or recently published trial.

If a scenario was being written about Adult Coeliac Disease what would the assessor include?

  • For acute disease: some form of diarrhoea (not bloody or with mucus), recent onset but with a history of recurrence over months, weight loss, may not always be related to intake of wheat as adult will have been on wheat all their lives, evidence of malabsorption such as anemia (iron deficiency, folate and vitamin B 12 deficiency, vitamin D deficiency). What tests you will be expected to do to prove that it is coeliac disease: intestinal biopsy for villous atrophy and some tests for gluten enteropathy such as autoantibodies; anti-endomysial antibody (EMA-IgA), anti-tissue transglutaminase antibodies (tTG) (tTG-IgA, tTG-IgG), or antibodies targeting gliadin, antibody to native gliadin: anti-gliadin antibody (AGA-IgA, AGA-IgG), antibodies against synthetic deamidated gliadin peptides: Deamidated gliadin peptide (DGP)-IgA, DGP-IgG. Anti-gliadin antibodies are unreliable as there are too many false positives. Undetectable IgA levels but not partial immunoglobulin A deficiency (low but detectable serum IgA) decreases the sensitivity of TTG-IgA.
  • Points in the scenario may give probability of disease: low probability; absence of suggestive signs or symptoms of malabsorption such as significant chronic diarrhea/steatorrhea or weight loss,, absence of family history of celiac disease, Chinese, Japanese, or Sub-Saharan African descent. High probability is likely if there are symptoms suggestive of intestinal coeliac disease or evidence of extra-intestinal diseases; malabsorption or nutrient deficiency plus risk factors such as first and second degree relative with confirmed celiac disease Type 1 diabetes, autoimmune thyroiditis, Down and Turner syndromes, pulmonary hemosiderosis (moderate risk).
  • What is the value of doing HLA testing? Only a 12% negative value if the usual HLA typing is absent. If HLA DQ2/DQ8 is negative, celiac disease is excluded.
  • These need to be excluded: irritable bowel syndrome, small intestinal bacterial overgrowth, lactose intolerance, chronic pancreatitis, microscopic colitis, and inflammatory bowel disease. Celiac disease can be differentiated from these by serologic evaluation and small bowel biopsy.
  • Why follow up coeliac disease? To correct the nutrient deficiency and look out for malignancy.

Whenever you are revising for an interactive assessment pick out the salient points and not just remember them but understand them.

Intermittent Fasting; how does it help.

When rodents are kept in captivity they are usually given their food in one go which they eat in one or two hours and then they fast for 22 hours. Most carnivores in nature eat one meal a day or maybe even every other day, depending on if they can find food to eat. Even the lordly lion goes hungry sometimes. Why did humans develop the three meals a day plus snacks habit and is this the best regime? In a 1997 article in the New England Journal, Weindruch and Sohal showed that reducing food availability over a lifetime (caloric restriction) has remarkable effects on aging and the life span in animals. May be it is good news that in a world which has managed to overpopulate itself, mismanaged both food production, equity of food availability, and climate change a bit of hunger is good for the human race. Hundreds of studies in animals and scores of clinical studies of controlled intermittent fasting regimens have been conducted in which metabolic switching from liver-derived glucose to adipose cell–derived ketones occurs daily or several days each week.

This image given below also taken from NEJM shows that the nucleus has to deal with stress which it tries to reduce, proteostasis and autophagy (remember that the proteins in our bodies are not only metabolically active molecules but also serve the function of growth, repair and endocrine signalling and also need to be removed when no longer needed but may also serve as sources of food and energy), regulate glucose and fat metabolism, mitochondrial biogenesis and cell survival. Hence health and stress resistance are closely linked to each other.

Many of the health benefits of intermittent fasting are not simply the result of reduced free-radical production or weight loss. Intermittent fasting is an evolutionarily conserved, adaptive cellular response that is integrated between and within organs in a manner that improves glucose regulation, increases stress resistance, and suppresses inflammation. Remember well stocked shelves in grocery stores have only recently become a feature of our lives. We need our hunter-gatherer reponses to stay healthy and stress free. During fasting, cells activate pathways that enhance intrinsic defenses against oxidative and metabolic stress and those that remove or repair damaged molecules. During the feeding period, cells engage in tissue-specific processes of growth and plasticity. However, most people consume three meals a day plus snacks, so intermittent fasting does not occur.

Preclinical studies consistently show the robust disease-modifying efficacy of intermittent fasting in animal models on a wide range of chronic disorders, including obesity, diabetes, cardiovascular disease, cancers, and neurodegenerative brain diseases. Periodic flipping of the metabolic switch not only provides the ketones that are necessary to fuel cells during the fasting period but also elicits highly orchestrated systemic and cellular responses that carry over into the fed state to bolster mental and physical performance, as well as disease resistance.

Studies in animals and humans have shown how intermittent fasting affects general health indicators and slows or reverses aging and disease processes. During periods of fasting, triglycerides are broken down to fatty acids and glycerol, which are used for energy. The liver converts fatty acids to ketone bodies, which provide a major source of energy for many tissues, especially the brain, during fasting. In the fed state, blood levels of ketone bodies are low, and in humans, they rise within 8 to 12 hours after the onset of fasting, reaching levels of 0.2 to 0.5 mM, which are maintained through 24 hours, with a subsequent increase to 1 to 2 mM by 48 hours. In rodents, an elevation of plasma ketone levels occurs within 4 to 8 hours after the onset of fasting, reaching millimolar levels within 24 hours. Intermittent fasting in humans should be recommended for 12-18 hours. The three most widely studied intermittent-fasting regimens are alternate-day fasting, 5:2 intermittent fasting (fasting 2 days each week), and daily time-restricted feeding as recommended above.

Why do we need to switch to a ketone based metabolism? Ketone bodies are not just fuel used during periods of fasting; they are potent signaling molecules with major effects on cell and organ functions. Ketone bodies regulate the expression and activity of many proteins and molecules that are known to influence health and aging. These include peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α), fibroblast growth factor 21,22,23 nicotinamide adenine dinucleotide (NAD+), sirtuins,24 poly(adenosine diphosphate [ADP]–ribose) polymerase 1 (PARP1), and ADP ribosyl cyclase (CD38).25 By influencing these major cellular pathways, ketone bodies produced during fasting have profound effects on systemic metabolism. Moreover, ketone bodies stimulate expression of the gene for brain-derived neurotrophic factor, with implications for brain health and psychiatric and neurodegenerative disorders.

Some improvements are caused by weight loss: such as improvements in glucose regulation, blood pressure, and heart rate; the efficacy of endurance training; and abdominal fat loss. Intermittent fasting stimulates autophagy and mitophagy while inhibiting the mTOR (mammalian target of rapamycin) protein-synthesis pathway. These responses enable cells to remove oxidatively damaged proteins and mitochondria and recycle undamaged molecular constituents while temporarily reducing global protein synthesis to conserve energy and molecular resources. These pathways are untapped or suppressed in persons who overeat and are sedentary.

Does intermittent fasting affect aging and longevity? Goodrick and colleagues reported that the average life-span of rats is increased by up to 80% when they are maintained on a regimen of alternate-day feeding, started when they are young adults. However, the magnitude of the effects of caloric restriction on the health span and life span varies and can be influenced by sex, diet, age, and genetic factors. In two. trials, overweight women (approximately 100 women in each trial) were assigned to either a 5:2 intermittent-fasting regimen or a 25% reduction in daily caloric intake. The women in the two groups lost the same amount of weight during the 6-month period, but those in the group assigned to 5:2 intermittent fasting had a greater increase in insulin sensitivity and a larger reduction in waist circumference. Young men who fast daily for 16 hours lose fat while maintaining muscle mass during 2 months of resistance training.

In a clinical trial, older adults on a short-term regimen of caloric restriction had improved verbal memory. There is certainly a need to undertake further studies of intermittent fasting and cognition in older people, particularly given the absence of any pharmacologic therapies that influence brain aging and progression of neurodegenerative diseases.

How can we use intermittent fasting in clinical practice?

Weight loss: in a 12-month study comparing alternate-day fasting, daily caloric restriction, and a control diet, participants in both intervention groups lost weight but did not have any improvements in insulin sensitivity, lipid levels, or blood pressure, as compared with participants in the control group.

Cardiovascular health: Intermittent fasting improves multiple indicators of cardiovascular health in animals and humans, including blood pressure; resting heart rate; levels of high-density and low-density lipoprotein (HDL and LDL) cholesterol, triglycerides, glucose, and insulin; and insulin resistance. In addition, intermittent fasting reduces markers of systemic inflammation and oxidative stress that are associated with atherosclerosis. The CALERIE (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) study showed that a 12% reduction in daily calorie intake for a period of 2 years improves many cardiovascular risk factors in nonobese persons.

Cancer: Specific intermittent-fasting regimens vary among studies, but all involve imposition of intermittent fasting during chemotherapy. Clinical trials of intermittent fasting in patients with cancer have been completed or are in progress. Most of the initial trials have focused on compliance, side effects, and characterization of biomarkers. For example, a trial of daily caloric restriction in men with prostate cancer showed excellent adherence (95%) and no adverse events. No studies have yet determined whether intermittent fasting affects cancer recurrence in humans.

Epidemiologic data suggest that excessive energy intake, particularly in midlife, increases the risks of stroke, Alzheimer’s disease, and Parkinson’s disease. There is strong preclinical evidence that alternate-day fasting can delay the onset and progression of the disease processes in animal models of Alzheimer’s disease and Parkinson’s disease.

Weight loss reduces the symptoms of asthma in obese patients. In one study, patients who adhered to the alternate-day fasting regimen had an elevated serum level of ketone bodies on energy-restriction days and lost weight over a 2-month period, during which asthma symptoms and airway resistance were mitigated. A reduction in symptoms was associated with significant reductions in serum levels of markers. Multiple sclerosis is an autoimmune disorder characterized by axon demyelination and neuronal degeneration in the central nervous system. Alternate-day fasting and periodic cycles of 3 consecutive days of energy restriction reduce autoimmune demyelination and improve the functional outcome in a mouse model of multiple sclerosis (experimentally induced autoimmune encephalomyelitis). Two recent pilot studies showed that patients with multiple sclerosis who adhere to intermittent-fasting regimens have reduced symptoms in as short a period as 2 months. Because it reduces inflammation,17 intermittent fasting would also be expected to be beneficial in rheumatoid arthritis, and indeed, there is evidence supporting its use in patients with arthritis.

Preclinical studies and clinical trials have shown that intermittent fasting has broad-spectrum benefits for many health conditions, such as obesity, diabetes mellitus, cardiovascular disease, cancers, and neurologic disorders. Animal models show that intermittent fasting improves health throughout the life span, whereas clinical studies have mainly involved relatively short-term interventions, over a period of months. Young adults are probably better subjects for intermittent fasting which may not be sustainable in older people in whom the effect may not be so well observed.

Differentiating the causes of weight loss, diarrhoea. Another case another disease.

A 23 year old woman presented to the OPD of her hospital with palpitation. Her description was “My heart thuds so fast that I think it is going to burst. It drums in my ear, goes fast and sometimes slower and takes hours to settle to a steady beat after I have rested for hours, had some water and something to eat and sometimes I have to go to a doctor who gives me some tablets and oxygen to inhale in his clinic I get dizzy and breathless. Sometimes I cough a lot and bring up phlegm tinged with blood. My heart always beats faster than when I was well all the time and goes fast and slow.”

When were you well and what symptoms did you have to begin with before the palpitation began?

She had developed diarrhoea six months ago. She passed 3-6 semi-formed stools a day without mucus or blood. She had a good appetite. had no abdominal cramps and has lost 6 kg weight during this time. She has no fever, night sweats, abdominal bloating, heartburn or rectal discomfort on passing stool. She did not pass urine in excess nor feel unduly thirsty. She lived with her husband who was healthy, her mother in law who had been treated for pulmonary tuberculosis a year back and was now in good health and was asymptomatic. Her two year old son and 5 year old daughter had received BCG vaccination as part of their childhood vaccination program and were in apparent good health. Her husband was the breadwinner. He was a carpenter, rented a comfortable house with electricity and running water and the family ate meat, chicken, vegetables, fruit and dal daily and had access to a government hospital in a nearby town.

What do we need to learn more about the diarrhoea? We know the frequency and consistency and that there is no blood or mucus so is unlikely to be from the large gut or an infection. Is the diarrhoea infective, inflammatory in nature or non-inflammatory? Is it secretory or osmotic or malabsorptive in character? There is no fever, night sweats, abdominal pain or colic. She does not complain of proctitis i.e. pain during defecation and does not give symptoms suggestive of anorectal fistula or abscess so the diarrhoea is non-inflammatory most probably. Type 1 diabetes, hyperthyroidism, other metabolic causes of diarrhoea, malabsorption, adult celiac disease?

Characterisation of diarrhoea.

  • Watery diarrhea – The water content of chronic diarrhea can be caused by secretory or osmotic processes, or a combination of the two. Measure fecal electrolytes, pH, reducing substances and calculate the osmotic gap.
  • Secretory diarrhoea occurs in cholera and carcinoid. It is large in volume and persists on fasting.
  • Osmotic – Osmotic (or “substrate-induced” or “diet-related” or overeating) diarrhea typically is less voluminous than secretory diarrhea (eg, <200 mL per day), and improves or resolves during 12- to 24-hours of fasting. The presence of reducing substances or low fecal pH (ie, pH <6) suggest carbohydrate malabsorption.
  • Fatty diarrhea – Malabsorption is often accompanied by steatorrhea and the passage of bulky malodorous pale stools.
  • Inflammatory diarrhea – Inflammatory forms of diarrhea typically present with liquid loose stools with blood. Elevation in fecal calprotectin (a protein found in neutrophil granulocytes) indicates an inflammatory diarrhea.

You need to ask the appropriate questions to elicit this information even if you have noticed the goitre in your observation.

She has no symptoms suggestive of diabetes like polyuria, polydipsia and polyphagia but fewer than 30% have these symptoms so don’t rely on them. Check out her fasting blood sugar and HbA1c.

The problem is solved when you examine her. The pulse is 110/min, irregular; she is afebrile; BP is 110/70 mmHg; her thyroid is diffusely enlarged with no bruit or cystic feel to it; she has lidlag but no prominent proptosis and is not in heart failure nor does she have a valve lesion; there is a fine tremor in the outstretched hands. The diarrhoea is caused by hyperthyroidism.

The problems you will have to sort out and be asked about are

  • How to handle her AF; whether to anticoagulate or not; rate control or rhythm control; what rate to keep her pulse at.
  • What treatment is best for he to control her hyperthyroidism; pros and cons of propylthiouracil and its indications; how long to treat; use of beta blocker; when to prescribe radio iodine; what to do in pregnancy; teratogenic effects of the different drugs.
  • How to treat the diarrhoea.
  • How to treat the tremors.
  • How to get her weight up.
  • What is the pathophysiology behind the symptoms.
  • How to investigate her.
  • Interpretation of the tests.
  • What to do if she gets pregnant.
  • Diagnosis and treatment of a thyroid crisis.
  • How to treat proptosis.
  • What are the surgical options for Graves ophthalmopathy.
  • What is the response time and how to monitor the patient.
  • What is the relapse rate.

I will leave you to find out the answers and then you will be well prepared for a viva.

Evaluating chronic diarrhoea in an adult.

A 44-year-old man was evaluated at this hospital because of diarrhea, weight loss, and abdominal pain and irregular fever . Approximately 6 months before admission, the patient began to have early satiety, nausea approximately 30 minutes after eating small amounts of food, and intermittent anorexia. He began to consume primarily liquids, khichdi and sabudana for breakfast and lunch and would skip dinner; during the next 5 months, he lost 9 kg. His primary care physician gave him him metronidazole for five days to no avail.

Using metronidazole for chronic diarrhoea is a common mistake made in a third world country. It should not be used unless amoebiasis is confirmed. Watery diarrhoea is rarely associated with amoebiasis nor is fever. Amoebiasis may be asymptomatic or have may a subacute onset, usually over one to three weeks. Symptoms range from mild diarrhea to severe dysentery, producing abdominal pain (12 to 80 percent), diarrhea (94 to 100 percent), and bloody stools (94 to 100 percent), to fulminant amebic colitis. Rarely, acute fulminant necrotizing amebic colitis presents with life-threatening lower gastrointestinal bleeding without diarrhea. Weight loss occurs in about half of patients, and fever occurs in less than 38 percent. Mucus is present in stools.

The differential diagnosis of bloody diarrhea other than E. histolytica includes other causes of acute diarrhea or bloody stools, particularly bacterial pathogens including Shigella, Escherichia coli, Salmonella, Campylobacter, Clostridioides (formerly Clostridium) difficile, and some Vibrio species. Tools for the diagnosis of intestinal amebiasis include stool microscopy, stool antigen detection, stool polymerase chain reaction (PCR), serology, and colonoscopy with histologic examination. Metronidazole is used for amoebic dysentery and extra intestinal amoebic disease and (off the label) giardiasis and Crohn’s disease. It is used in H pylori eradication, anaerobic periodontal disease, skin infection and pneumonia and Cl difficile infection but not in acute watery diarrhoea. Using it in acute watery diarrhoea, chronic watery diarrhoea and suspected malabsorption is counterproductive and gives a poor impression in an examination candidate.

New, near-constant epigastric pain developed, approximately 1 hour after meals, nausea and vomiting occurred, with diffuse abdominal bloating and cramping. In addition, watery diarrhea began to occur twice daily, without hematochezia or melena. One week after discharge, the patient’s primary care physician prescribed omeprazole. The patient lost an additional 14 kg weight loss. The patient’s medical history was notable for depression, lumbar pain, and vitamin D deficiency. Intermittent diffuse headache persisted in the 3 weeks after discharge from the other hospital, and the patient reported low-grade fever. A review of systems was negative for night sweats, chills, neck pain, photophobia, vision changes, chest pain, dyspnea, cough, coryza,sore throat, oral ulcers, back pain, dysuria, hematuria, rashes, joint or muscle pain, edema, and pruritus. Medications included venlafaxine, cholecalciferol, and omeprazole. The patient took an herbal supplement of unknown type in the week after discharge from hospital. He had never used nonsteroidal antiinflammatory drugs. He had no known medication allergies. Approximately 3 weeks later, he presented to the emergency department of this hospital for evaluation again. He was dehydrated, the BP was 90/50 mmHg there was anemia, glossitis, angular stomatitis and cheilitis, he looked emaciated and had mild edema. His eyes were prominent, the thyroid was not enlarged. He had mild tremors in his hands. The lymph nodes were not enlarged.

Have these symptoms got any relationship to his medication? PPI use is associated with an increased risk of C. difficile infection, even in the absence of antibiotic use. Associations with other enteric infections, including salmonellosis and campylobacteriosis, have also been reported. However, the pathophysiologic mechanism involved in the increased risk of infection is unclear. PPI use has been associated with microscopic colitis, including lymphocytic and collagenous colitis. Cl difficile infection causes mild to severe bloody diarrhoea usually in people taking antibiotics such as fluoroquinolones, clindamycin, cephalosporins, and penicillins, though virtually any antibiotic can predispose to CDI. Do not use omeprazole indiscriminately in chronic diarrhoea unless you have a specific diagnosis in mind and then monitor the patient carefully.

How much importance should you give in your diagnostic evaluation to the tremor, prominent eyes, weight loss when the thyroid is not enlarged? Hyperthyroidism may present as diarrhoea but the other symptoms can be explained on the weight loss from the malabsorption caused by his chronic diarrhoeal illness. TSH at least needs to be checked but don’t base your whole diagnosis on hyperthyroidism.

The patient was discharged after IV fluids, oral rehydration salts, ciprofloxacin, and sucralfate and dicyclomine were given orally. and a diet of rice, yogurt, bland vegetables, chicken broth and lentils was advised. Wheat and gluten was avoided in the diet. Oral vitamin B complex and vitamin D were also given. 3 weeks after discharge the patient reported low-grade fever. A review of systems was negative for night sweats, chills, neck pain, photophobia, chest pain, dyspnea, cough, coryza, sore throat, oral ulcers, back pain, dysuria, hematuria, rashes, joint or muscle pain or pruritus. The patient was admitted to hospital again. Diarrhea and abdominal pain persisted on the second hospital day.

Tests for human immunodeficiency virus (HIV) type 1 and type 2 antibodies and antigen, Treponema pallidum antibodies, Clostridium difficile antigen, and tissue transglutaminase IgA were negative. Blood testing for Helicobacter pylori IgG was positive; however, a stool test for H. pylori antigen was negative.

This 44-year-old man presentswith a subacute gastrointestinal illness that is
characterized by epigastric pain, vomiting, diarrhea, and progressive weight loss during a 6-month period, Laboratory findings are notable for marked hypoalbuminemia, elevated levels of inflammatory markers, an elevated fecal calprotectin level, and a fluctuating absolute eosinophil count that approaches the threshold for eosinophilia (1500 cells), A CT abdomen showed air and fluid filled loops of the intestine with loss of folds in the duodenum and loss of haustrations in the colon, engorged mesenteric vessels and an enlarged mesenteric lymph node,

This patient lives in a slum in Karachi, with overcrowding, and his income is below the poverty line. Infection specially with Mycobacterium tuberculosis, bovis and avium must be considered and excluded. HIV testing must be repeated as M. avium may be a cause of diarrhoea associated with AIDs. Intestinal tuberculosis occurs in the absence of pulmonary infection or symptoms as milk and food nay be the source of the infection.

Whipple’s disease must be ruled out in this case. Whipple’s disease may be manifested by a subacute wasting illness. Infection with Tropheryma whipplei leads to infiltration of foamy macrophages into the small bowel, which results in a syndrome of abdominal pain, diarrhea, and malabsorption that is typically accompanied by joint pain. Other extraintestinal features include fever,
lymphadenopathy, and central nervous system abnormalities, such as dementia, cerebellar ataxia, and in rare cases, oculomasticatory myorhythmia. The diagnosis of Whipple’s disease can be made by periodic acid–Schiff staining of a small-bowel biopsy specimen, which would show foamy macrophages in the lamina propria of the gut.

Cancer must be included in the differential diagnosis, a malignant process seems unlikely, given the diffuse nature of the intestinal abnormality seen on CT imaging; nevertheless, consider the possibility of lymphoma. The gastrointestinal tract is the most common extranodal site of lymphoma. small-bowel lymphoma accounts for most cases. This patient has evidence of H. pylori infection,which may contribute to lymphoma involving the mucosa-associated lymphoid tissue of the stomach. The Mediterranean variety of small-bowel lymphoma, known as immunoproliferative small intestinal disease, may be manifested by abdominal pain, diarrhea, malabsorption, and weight loss. The other small-bowel lymphomas
include enteropathy-associated T-cell lymphoma (associated with celiac disease), Burkitt’s lymphoma, and B-cell lymphomas other than immunoproliferative small intestinal disease.

Autoimmune Disease
Celiac disease, which can cause a subacute syndrome of diarrhea and weight loss as well as hypoalbuminemia and evidence of mucosal hyperemia on imaging, is a consideration in this case. This patient had a negative tissue transglutaminase IgA test, but the total IgA level is not reported. When considering celiac disease, it is
important to first rule out concomitant IgA deficiency.

Autoimmune enteropathy is a rare disorder that can lead to subacute diarrhea and weight loss. It is characterized by a lymphocytic immune reaction that causes enterocyte destruction and intestinal villous blunting that can mimic severe celiac disease.

Strongyloides is a very unlikely possibility as the part of the world this patient lives in does not expose him to the proximity of pigs and swine hence this parasite which is common elsewhere as in African and Caribbean countries, is unlikely to have invaded him.

With the information provided here there is ample material for a good discussion.