Antiphospholipid antibody syndrome (APS)

From The Lancet:

Graham Hughes, who first described antiphospholipid syndrome (APS) in 1983, urged for more efforts to raise awareness of this disorder. APS often remains undiagnosed and untreated with catastrophic consequences, such as multiple miscarriages, or stroke at a young age.

Clinical features of APS

Clinical manifestations of antiphospholipid syndrome (APS) include:

- venous, arterial, and small-vessel thrombosis

- pregnancy loss

- preterm delivery for patients with severe pre-eclampsia or placental insufficiency

- cardiac valvular disease

- renal thrombotic microangiopathy

- thrombocytopenia

- haemolytic anaemia

- cognitive impairment

Antibodies

Antiphospholipid antibodies promote activation of endothelial cells, monocytes, and platelets; and overproduction of tissue factor and thromboxane A2 (procoagulants). Complement activation might have a central pathogenetic role.

The coagulation cascade. Black arrow - conversion/activation of factor. Red arrows - action of inhibitors. Blue arrows - reactions catalysed by activated factor. Grey arrow - various functions of thrombin. Image source: Wikipedia

Of the different antiphospholipid antibodies, lupus anticoagulant is the strongest predictor of clinical presentation.

Treatment of APS

Therapy of thrombosis is based on long-term oral anticoagulation (warfarin). Patients with arterial events should be treated aggressively.

Primary thromboprophylaxis is recommended in patients with systemic lupus erythematosus (SLE) and in obstetric antiphospholipid syndrome. Obstetric care is based on treatment with aspirin and heparin.

Hydroxychloroquine is a potential additional treatment for APS. Possible future therapies for non-pregnant patients with antiphospholipid syndrome are statins, rituximab, and new anticoagulant drugs.

References

Antiphospholipid syndrome. The Lancet, Volume 376, Issue 9751, Pages 1498 - 1509, 30 October 2010.

Raising awareness of antiphospholipid antibody syndrome. The Lancet, Volume 375, Issue 9717, Page 778, 6 March 2010.

Munchausen's syndrome - NHS video

From the NHS Choices YouTube channel: A psychiatrist explains the motivation behind Munchausen's syndrome, also known as factitious illness, where someone pretends to be ill or causes symptoms in themselves. This can include inflicting wounds or tampering with blood and urine samples. He also explains the importance of getting treatment and describes another form of the condition where a person fabricates an illness in someone in their care (Munchausen's syndrome by proxy):



Comments from Twitter:

Julie Meadows-Keefe @esq140: Fascinatingly & disturbingly real.

Marfan syndrome - Mayo Clinic video summary

In this video Juan Bowen, M.D., director of Mayo Clinic Marfan Clinic, discusses causes of Marfan syndrome and the importance of diagnosis and treatment:

Obesity Hypoventilation Syndrome (OHS) - Mayo Clinic video

From Mayo Clinic: "The CDC statistics are alarming. More than one-third of adults in the U.S. are obese. You likely know that obesity can increase your risk of diseases such as high blood pressure, diabetes and heart attack. But you might not know that it also increases your risk of a condition called obesity hypoventilation syndrome, or OHS." If left untreated, OHS can diminish quality of life and even cause heart failure.

Obesity hypoventilation syndrome (OHS) is a condition in obese people in which poor breathing leads to lower oxygen and higher carbon dioxide levels in the blood. Obesity Hypoventilation Syndrome (OHS) exists when an obese individual (body mass index (BMI) greater than 30kg/m2) has awake alveolar hypoventilation (PaCO2 greater 45 mmHg), which cannot be attributed to other conditions such as pulmonary disease, skeletal restriction, neuromuscular weakness, hypothyroidism, or pleural pathology.



Obesity Hypoventilation Syndrome (OHS) is a well-known cause of hypoventilation. Abnormal central ventilatory drive and obesity contribute to the development of OHS.

OHS is defined as a combination of:

- obesity
- a body mass index greater than or equal to 30kg/m2 with awake chronic hypercapnia (PaCO2 greater than 45 mm Hg)
- sleep-disordered breathing

Other disorders that may cause hypoventilation should be ruled out first. Approximately 90% of patients with OHS also have obstructive sleep apnea (OSA).

References:

What Is Obesity Hypoventilation Syndrome? - NHLBI, NIH http://buff.ly/1lholgO
Hypoventilation Syndromes - Medscape http://buff.ly/1lhocdk
Clinical manifestations and diagnosis of obesity hypoventilation syndrome - UpToDate http://buff.ly/NtaRjP
Obesity hypoventilation syndrome (OHS): MedlinePlus Medical Encyclopedia http://buff.ly/1lho8KH

Middle East Respiratory Syndrome (MERS): Threats Posed by the Virus (WSJ video)

An Indiana patient with the first case of Middle East Respiratory Syndrome (MERS) reported in the U.S. is stable. But the MERS virus has proved deadly elsewhere. What kind of threat does the virus present? Columbia University's Dr. W. Ian Lipkin discusses with the WSJ:



MERS was first identified in June 2012. Arabian camels were recently identified as the source of the respiratory virus. To date, there have been 401 confirmed cases of MERS in 12 countries, but all the cases originated in 6 countries in the Arabian Peninsula. More than 100 people have died.

New research has confirmed that camels can transmit the deadly MERS virus to people. Virologists at the University of Veterinary Medicine in Vienna, Austria, found that the Middle East Respiratory Syndrome viruses in camels and people in the same geographical region are almost genetically identical.

MERS is closely related to the SARS virus, which arose in China and killed 800 people worldwide in 2002 and 2003. "While the SARS coronavirus probably crossed the species barrier only once by passing from bats to humans, we may presume that the MERS coronavirus is being constantly transmitted from camels to humans", said the researchers.

References:

MERS Can Be Transmitted From Camel to Human, Study Confirms – WebMD http://buff.ly/1s5Gw8h

Erythromelalgia - The Syndrome of Red, Hot Feet - Mayo Clinic video

Erythromelalgia is the name applied to the clinical syndrome of red, hot extremities. Most often, the feet are involved; less often the hands are also involved; rarely, the face (ears especially) may be involved. This short video describes what this syndrome is, what is known about why it happens, how it is diagnosed and managed. Here is a Mayo Clinic video about erythromelalgia:



Erythromelalgia is a rare disorder that is characterized by burning pain and warmth and redness of the extremities. There is primary (idiopathic) and secondary erythromelalgia (most commonly associated with myeloproliferative disorders).

The name is derived from 3 Greek words: erythros (“red”), melos (“limb”), and algos (“pain”).

Pelated:

JAMA Dermatology | Erythromelalgia: Vasculopathy, Neuropathy, or Both? http://buff.ly/1uTVen2
Erythromelalgia - Medscape http://buff.ly/1uTV7Ii
Erythromelalgia - NIH Genetics Home Reference http://buff.ly/1iFFA5g
Paroxysmal burning pain caused by erythromelalgia : The Lancet http://buff.ly/1nuzN7X

Myelodysplastic Syndrome - Mayo Clinic videos

What is Myelodysplastic Syndrome (MDS)? Raoul Tibes, M.D., Ph.D., hematologist at Mayo Clinic in Arizona, provides an overview of myelodysplastic syndrome (MDS) including the symptoms and diagnosis.



Myelodysplastic Syndrome Treatment. Raoul Tibes, M.D., Ph.D. discusses various treatment options available for individuals diagnosed with myelodysplastic syndrome.

Neurological and autoimmune disorders after influenza vaccination: no change in risk for Guillain-Barré syndrome, MS, type 1 diabetes, or RA

This Swedish retrospective cohort study, published in BMJ, examined the risk of neurological and autoimmune disorders in people vaccinated against pandemic influenza A (H1N1) with Pandemrix (GlaxoSmithKline) compared with unvaccinated people over 8-10 months.


Image of the H1N1 Influenza Virus, CDC.

One million people were vaccinated against H1N1 and 900,000 remained unvaccinated.

Excess risks among vaccinated people were of low magnitude, but present, for:

- Bell’s palsy (hazard ratio 1.25)
- paresthesia (1.11)
- inflammatory bowel disease (IBD)

Risks for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis remained unchanged.

The risks of paresthesia and inflammatory bowel disease (IBD) among those vaccinated in the early phase (within 45 days) of the vaccination campaign were significantly increased; the risk being increased within the first 6 weeks after vaccination.

The risks were small but significant among more than one million vaccinated, but only in high risk groups targeted for early vaccination and who were likely to have earlier comorbidity.

The absolute risk of Bell’s palsy was low, 6.4 cases per 100 000 vaccinated population.

References:

Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden. BMJ 2011; 343:d5956 doi: 10.1136/bmj.d5956 (Published 12 October 2011).

Premenstrual syndrome and premenstrual dysphoric disorder (review)

Premenstrual syndrome

Premenstrual syndrome is defined as recurrent psychological and physical symptoms that occur during the luteal phase of menses and resolve with menstruation. It affects 20-30% of premenopausal women.

Premenstrual dysphoric disorder

Premenstrual dysphoric disorder includes affective or somatic symptoms that cause severe dysfunction in social or occupational activity. It affects 3-8% of premenopausal women.

Proposed etiologies (causative factors) include:

- increased sensitivity to normal cycling levels of estrogen and progesterone
- increased aldosterone and plasma renin activity
- neurotransmitter abnormalities, particularly serotonin

The Daily Record of Severity of Problems is one tool with which women may self-report premenstrual symptoms.

Symptom relief is the goal, and there is limited evidence for the use of:

- calcium
- vitamin D
- vitamin B6 supplementation

Serotonergic antidepressants (SSRIs) (citalopram, escitalopram, fluoxetine, sertraline, venlafaxine) are first-line pharmacologic therapy.

References:

Premenstrual syndrome and premenstrual dysphoric disorder. Biggs WS, Demuth RH. Am Fam Physician. 2011 Oct 15;84(8):918-24.

Image source: OpenClipArt.org, public domain.

Back and forth: Study fails to show link previously found between virus and chronic fatigue syndrome

A UK study analysing samples from patients with chronic fatigue syndrome has found no evidence of a link with a retrovirus (XMRV). The virus was first described in 2006.

Patients with chronic fatigue syndrome, also known as myalgic encephalomyelitis, often report that their condition—a mix of symptoms including extreme fatigue—began after an otherwise normal viral infection.

The xenotropic murine leukaemia virus-related virus (XMRV) was found in 67% of patients with chronic fatigue syndrome in a study reported last year (Science 2009,326:585-9).


The Gift of Time is a short film about the doctors who discovered the XMRV virus and the breakthru potential for prostate cancer.

References:

Study fails to show link previously found between virus and chronic fatigue syndrome. BMJ 2010;340:c1033.

Takotsubo cardiomyopathy (broken-heart syndrome) in differential diagnosis of chest pain

Takotsubo cardiomyopathy (also called stress induced cardiomyopathy, apical ballooning, or broken heart syndrome) was first described in Japan 20 years ago. It is typically precipitated by acute emotional stress, hence the names “stress cardiomyopathy” or “broken-heart syndrome.”

Takotsubo cardiomyopathy is characterised by acute, reversible left ventricular dysfunction in a distribution,which does not correlate with the coronary artery blood supply. The left ventricular dysfunction occurs without obstructive coronary artery disease (CAD) and usually resolves spontaneously over a period of weeks.

The characteristic appearances on contrast angiography include:

- ballooned apical segment

- hypercontractile basal portion of the left ventricle

The appearances are reminiscent of the design of the traditional fishing pot used in Japan to trap octopus, hence the descriptive term "tako-tsubo" cardiomyopathy (octopus trap, tako tsubo). Such a trap, no more than simple ceramic jar, take advantage of the octopus’ preference for small, enclosed spaces and the security they seem to promise. They are simply left on the seabed and gathered later after octopi have had time to occupy them.

Although Takotsubo cardiomyopathy was initially considered rare, it could possibly be responsible for 1-2% of admissions for acute coronary syndrome in industrialised countries.

"Takotsubo Cardiomyopathy Caught on Tape" - Jems.com YouTube channel.

References:
Takotsubo cardiomyopathy. Banning et al. 340: c1272, BMJ.

Takotsubo Cardiomyopathy, or Broken-Heart Syndrome. SS Virani et al, Tex Heart Inst J. 2007; 34(1): 76–79.

Morikami museum.

Image source: Octopus trap, tako tsubo, Morikami museum.

Postural Orthostatic Tachycardia Syndrome (POTS) - Mayo Clinic video

Phil Fischer, M.D., discusses the latest research on Postural Orthostatic Tachycardia Syndrome (POTS). Two free full text reviews are available via Dr. RW Notes.

Postural Orthostatic Tachycardia Syndrome from a patient's perspective:



After 9 months of struggling and fighting for a diagnosis, she was diagnosed with Postural Orthostatic Tachycardia Syndrome (POTS).

POTS from a mother's perspective:

Comments from Twitter:

@drjohnm (John Mandrola, MD): For EPs, POTS is one tough nut to crack.>>Helpful video.

Celiprolol as treatment of choice to prevent complications in vascular Ehlers-Danlos syndrome

Vascular Ehlers-Danlos syndrome is a rare hereditary connective tissue disorder caused by mutations in the collagen type III gene ( COL3A1 ), which leads to a loss of tissue integrity in many organ systems.

Patients with vascular Ehlers-Danlos syndrome have weakened blood vessels and an increased risk of arterial dissection or rupture that can lead to early death.

The researchers assessed the ability of celiprolol, a β1-adrenoceptor antagonist with a β2-adrenoceptor agonist action, to prevent arterial dissections and ruptures in vascular Ehlers-Danlos syndrome.

Patients with clinical vascular Ehlers-Danlos syndrome were randomly assigned to 5 years of treatment with celiprolol or to no treatment.

33 patients were positive for mutation of collagen 3A1 (COL3A1). Celiprolol was uptitrated every 6 months by steps of 100 mg to a maximum of 400 mg twice daily. The primary endpoints were arterial events (rupture or dissection, fatal or not).

Mean duration of follow-up was 47 months, with the trial stopped early for treatment benefit.

The primary endpoints were reached by 20% in the celiprolol group and by 50% controls (hazard ratio [HR] 0·36).

Celiprolol might be the treatment of choice for physicians aiming to prevent major complications in patients with vascular Ehlers-Danlos syndrome.

References:

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. The Lancet, Volume 376, Issue 9751, Pages 1476 - 1484, 30 October 2010.

Celiprolol therapy for vascular Ehlers-Danlos syndrome. The Lancet, Volume 376, Issue 9751, Pages 1443 - 1444, 30 October 2010.