Mast Cell Activation Syndrome in Pregnancy, Delivery, Postpartum and Lactation: A Narrative Review
Shanda R Dorff et al. J Obstet Gynaecol. 2020
"The pathobiology of MCAS drives extraordinary clinical complexity and heterogeneity, which led to only recent recognition despite increasingly apparent substantial prevalence, perhaps as high as 17%. It also has a strong female predilection. Thus, MCAS inescapably impacts pregnancy and the post-partum period in many women.
No specific research in the pregnant or post-partum MCAS population has been performed yet. However, its prevalence and potential for driving substantial morbidity merit obstetric providersâ acquaintance with this illness and its potential impacts on their patients during pregnancy, delivery, the post-partum period, and lactation.
Extensive literature review across all medical specialities, plus direct experience in the authorsâ practices, provides guidance in recognising MCAS in pregnancy and diagnosing and effectively managing it.
Described herein are manners in which MCAS, a protean multisystem disease, adversely affects all stages of pregnancy and post-partum. In order to reduce risks of MCAS causing complications before, during and after pregnancy, identifying and controlling the syndrome prior to pregnancy is best, but, even if the disease is not recognised until late, there may still be opportunities to mitigate its effects. There is precedent for improved outcomes if comorbid MCAS is recognised and controlled.
This review provides the first comprehensive guide for obstetric providers regarding this emerging major comorbidity."
The role of mast cells in pediatric gastrointestinal disease
Naseem Ravanbakhsha, Anil Kesavanb
Rush University Childrenâs Hospital, Chicago, IL, USA
Pediatric MCAS includes primary, secondary, and idiopathic forms. Primary (clonal) MCAS is extremely rare in children and if present typically takes the form of CM, imited to the skin. Secondary MCAS is more prevalent in children and occurs secondarily to a variety of allergic and inflammatory conditions. Idiopathic MCAS is poorly understood and has not been clearly defined in the pediatric population.
Context Irritable bowel syndrome (IBS), which affects 11% to 14% of the population, is a puzzling condition with multiple models of pathophysiology including altered motility, visceral hypersensitivity, abnormal brain-gut interaction, autonomic dysfunction, and immune activation. Although no conceptual framework accounts for all the symptoms and observations in IBS, a unifying explanation may exist since 92% of these patients share the symptom of bloating regardless of their predominant complaint.
The gastrointestinal and immune effects of SIBO provide a possible unifying framework for understanding frequent observations in IBS, including postprandial bloating and distension, altered motility, visceral hypersensitivity, abnormal brain-gut interaction, autonomic dysfunction, and immune activation.
Zebra is the American medical slang for arriving at an exotic medical diagnosis when a more commonplace explanation is more likely.
It is shorthand for the aphorism coined in the late 1940s by Theodore Woodward, professor at the University of Maryland School of Medicine, who instructed his medical interns: âWhen you hear hoofbeats, think of horses not zebrasâ. Since horses are common in Maryland while zebras are relatively rare, logically one could confidently guess that an animal making hoofbeats is probably a horse. By 1960, the aphorism was widely known in medical circles.
As explained by Sotos, medical novices are predisposed to make rare diagnoses because of (a) the availability heuristic (âevents more easily remembered are judged more probableâ) and (b) the phenomenon first enunciated in Rhetorica ad Herennium (circa 85 BC), âthe striking and the novel stay longer in the mind.â Thus, the aphorism is an important caution against these biases when teaching medical students to weigh medical evidence.
Diagnosticians have noted, however, that âzebraâ-type diagnoses must nonetheless be held in mind until the evidence conclusively rules them out:
In making the diagnosis of the cause of illness in an individual case, calculations of probability have no meaning. The pertinent question is whether the disease is present or not. Whether it is rare or common does not change the odds in a single patient. ⌠If the diagnosis can be made on the basis of specific criteria, then these criteria are either fulfilled or not fulfilled. â A. McGehee Harvey, James Bordley II, Jeremiah Barondess.
The term for an obscure and rare diagnosis in medicine is fascinoma.
Hickamâs dictum is a counterargument to the use of Occamâs razor in the medical profession. While Occamâs razor suggests that the simplest explanation is the most likely, implying in medicine that diagnosticians should assume a single cause for multiple symptoms, one form of Hickamâs dictum states: âA man can have as many diseases as he damn well pleases.â The principle is attributed to John Hickam, MD.
Hickamâs dictum asserts that at no stage should a particular diagnosis be excluded solely because it does not appear to fit the principle of Occamâs razor.
The principle of Occamâs razor, or parsimony, does not demand that the diagnostician necessarily opt for the simplest explanation, but instead guides the medical practitioner to seek explanations, without unnecessary additional assumptions, which are capable of accounting for all relevant evidence.
A key reason for using Hickamâs dictum as a limiting principle to that of Occamâs razor is that it is often statistically more likely that a patient has several common diseases rather than having a single, rarer disease that explains their myriad symptoms. Another key reason is that, independent of statistical likelihood, some patients do in fact turn out to have multiple diseases. In such cases, multiple categories of diagnosis may indeed have independent causes rather than a single source, i.e., may be due to separate events or combinations of events to which the patient may have been subjected or exposed.
Thus, Hickamâs dictum provides physicians with a counterbalancing principle to the unfettered use of Occamâs razor in diagnosis. For example, Theodore Dalrymple, a career physician turned social critic, has written that multiple diseases or illnesses are the rule rather than the exception. He contends that adherence to medical parsimony is âa matter of taste more than of truth,â and that patients are routinely misdiagnosed by clinicians who insist on finding a single underlying cause for multiple symptoms.
To our knowledge there are no reported cases in the literature of patients diagnosed with MCAS or other idiopathic mast cell disorders undergoing radiation therapy. Idiopathic mast cell disorders such as MCAS and primary mast cell disorders alike should not be considered a contraindication to treatment with EBRT. This patient population appears to tolerate treatment without systemic flares in symptoms.
Recent advances in mast cell activation and regulation
Hwan Soo Kim
'When activated in an allergen- and immunoglobulin E (IgE)-dependent manner, these cells secrete a large variety of allergenic mediators that are pre-stored in secretory granules or de novoâsynthesized.
Traditionally, studies have predominantly focused on understanding this mechanism of mast cell activation and regulation. Along this line of study, recent studies have shed light on what structural features are required for allergens and how IgE, particularly anaphylactic IgE, is produced.
However, the last few years have seen a flurry of new studies on IgE-independent mast cell activation, particularly via Mrgprb2 (mouse) and MRGPRX2 (human). These studies have greatly advanced our understanding of how mast cells exert non-histaminergic itch, pain, and drug-induced pseudoallergy by interacting with sensory neurons.
Recent studies have also characterized mast cell activation and regulation by interleukin-33 (IL-33) and other cytokines and by non-coding RNAs.
These newly identified mechanisms for mast cell activation and regulation will further stimulate the allergy/immunology community to develop novel therapeutic strategies for treatment of allergic and non-allergic diseases.â
