Mycoplasma Pneumoniae and Hemolytic Anemia

Today we had the pleasure of a guest visit from Dr. Ho Ping-Kong, who walked us through a fascinating case of cold-agglutinin hemolytic anemia secondary to mycoplasma pneumoniae infection in a young man presenting with jaundice.

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in younger patients. It can cause both upper and lower respiratory tract infections. It typically has a prolonged and gradual onset, with prolonged paroxysmal cough. Its incubation period can be up to three weeks. Of note, although one of the most common causes of pneumonia in people younger than 40, only 10% of patients with mycoplasma pneumoniae infection will develop pneumonia.

Typically patients complain of fever, malaise, persistent dry cough, headache, chills, and coryza. Tracheal tenderness, chest soreness and pleuritic chest pain can occur, all because of the protracted cough. Patients typically do not appear unwell, and have nonspecific findings like pharyngeal injection and usually normal lung fields. Imaging can show bronchopneumonia, interstitial or reticulonodular infiltrates bilaterally (lower lobe predominance), and atelectasis.

Mycoplasma pneumoniae is associated with many extra-pulmonary manifestations, including acute hepatitis, ITP, cold-aggulitinin mediated autoimmune hemolytic anemia, arthritis, Stevens-Johnson syndrome, conduction abnormalities and transverse myelitis. These can occur before, during, after, or even in the absence of respiratory symptoms.

It is difficult to culture and, lacking a cell wall, cannot be seen on gram stain. Mycoplasma serology and PCR testing can be done. Cold agglutination testing is often positive, even in patients not actively hemolyzing. Often these cold agglutinants result in subclinical hemolysis and reticulocytosis.

In patients presenting with jaundice found to have hemolytic anemia, it is important to think of other potential causes of hemolysis - our patient had incidental G6PD deficiency! Similarly, mycoplasma pneumonia has been associated with chest crisis in sickle cell disease, making this an important entity to rule out as well.

Macrolides or doxycycline can be used against this atypical pneumonia. The complications of the pneumonia can be treated supportively. Patients who are hemolyzing should not be transfused if possible, as this can worsen the hemolysis. While admitted, patients should be under droplet precautions.

See here for a quick case report and review.

Vertigo in a hypertensive patient

Vertigo as a presenting complaint can be challenging diagnostically, but not when approached in a systematic, rational way. We discussed a case of a hypertensive patient of Western African origin who presented with vertigo, ultimately found to have a cerebellar stroke.

This case highlights a few key principles in the approach to vertigo:

1) Verify that this is truly vertigo - ie a sensation of oneself or the room spinning, as compared to presyncope or lightheadedness. The diagnostic approach for these 2 entities can be quite different.

2) Once you have decided that this is vertigo, decide whether it is of central (ie CNS) or peripheral (ie vestibular) etiology.

First, let's discuss what the central and peripheral causes are:

Peripheral

Benign positional paroxysmal

vertigo (transient, positional, caused by otoliths)

Ménière’s disease (recurrent vertigo, aural fullness, tinnitus, nausea, vomiting)

Acute labyrinthitis (typically viral)

Acute vestibular neuronitis (inflammation of the nerve, typically viral)

Cholesteatoma

Herpes zoster oticus (Ramsay Hunt syndrome)

Medication-related

Central

Cerebellopontine angle tumor

Cerebrovascular disease (TIA, Stroke, hemorrhage)

Migraine

Multiple sclerosis

Medication-related

There are several key features on history that can help differentiate between peripheral and central causes, in over 75% of cases.

Central:

• Longer duration of symptoms without relief
• Less severe nausea and vomiting
• More likely purely horizontal, rotatory, or vertical nystagmus that is not alleviated by fixing on an object
• Sudden only if cerebrovascular in nature
• Associated neurological symptoms/findings
• Cardiovascular risk factors
• Short latency after performing Dix-Hallpike before nystagmus

Peripheral

• Rotatory illusions
• Much more likely to have nausea and vomiting
• Nystagmus is often both horizontal and rotational, improving with fixing gaze, and usually triggered by some provoking factor (ie position)
• Often sudden onset
• Often associated with other symptoms: tinnitus, ear pain/fullness, hearing loss, recent viral illness
• Long latency after performing Dix-Hallpike before nystagmus

Physical examination should pay special attention to a full neurological examination (including gait), H&N examination looking at the tympanic membranes, orthostatic vitals, and performing a Dix-Hallpike Maneuver.

See here for a great review.

Lastly, it is important to note that this man was of Western African origin and quite young. Studies have shown that s

mall-vessel cerebrovascular disease and vascular-related cognitive impairment are more prevalent in hypertensive subjects of black African origin compared with Caucasians. This particular study found that

African-Caribbean subjects were typically 4 years younger but had been hypertensive for 3 years longer than Caucasians. They found that mean 24-hour BP was more poorly controlled in African-Caribbean patients and that ethnicity was independently related to

increased hypertensive white matter damage and executive cognitive dysfunction. Another study estimated that the higher BP in hypertensive black patients (as compared to Caucasions) results in 5480 more deaths due to heart disease and 2190 more deaths due to strokes in the US. It is important for us to consider why these differences in both risk factors and outcomes exist - access to healthcare and socioeconomic status being important factors. Interestingly, you may have seen in the news recently - the Annals of Internal Medicine published on culturally-appropriate storytelling (ie African-American patients describing their experiences with hypertension) as an intervention to lower BP - with fascinating results! See here.

Rapidly Progressive Dementia

Today we discussed a fascinating and very sad case of a woman with rapidly progressive dementia over a 3 week period. We discussed the broad differential diagnosis for this phenomenon which includes:

• Neurodegenerative conditions including Creutzfeldt-Jacob disease, other dementias and progressive supranuclear palsy.
• Infectious conditions like HSV encephalitis or HIV dementia, subacute sclerosing panencephalitis following measles infection in young adults, and syphilis.
• Metabolic conditions like B12 deficiency, Wernicke's encephalopathy from thiamine deficiency, and liver/renal failure.
• Toxins like Lead, Lithium, Mercury, Arseni, or bismuth.
• Autoimmune phenomenon like Hashimoto's encephalopathy, CNS vasculitis, or lupus cerebritis.
• Paraneoplastic limbic encephalopathy.
• Metastases or primary CNS malignancies.

We discussed the possibility of prion disease, or Creutzfeldt-Jacob disease at length today. CJD is a transmissible spongiform encephalopathy that is uniformly fatal - variant forms (ie acquired) often within 3 months and sporadic within 6. Although the incubation period is incredibly long (years), CJD progresses rapidly once symptoms appear. It is characterized by:

• dementia, diminished higher-level cortical function, and mood changes
• myoclonus
• extrapyramidal signs like hypokinesia and cerebellar signs like ataxia and nystagmus.

Diagnosis is made with the support of a number of modalities, most of which do not allow for rapid or definitive diagnosis, and lack sensitivity or specificity. These include MRI which often shows increased T2 and FLAIR signal intensity in the putamen and head of the caudate, EEG showing periodic synchronous bi- or triphasic sharp wave complexes (specific, not sensitive), and CSF (normal glucose, often (60%) normal protein levels, and presence of abnormal protein 14-3-3).

Unfortunately there is no treatment for CJD and death invariably occurs within months. This is all the more reason why it is important to search for the other, potentially reversible causes of rapidly progressing dementias. See this great review for a some very helpful algorithms outlining the approach to investigation.