Dignity

I have always been socially awkward. For most of my life, there has seemed to be this set of universally applicable rules that I don’t understand. In particular, I find that I am generally neither embarrassed by not impressed with a variety of circumstances that seem extraordinary to the general population. I am not the kind of person who is upset by immodesty or esoteric ideas or the rending of social rules. I never have been. I don’t know why.

The day before my colostomy surgery, I was lying on my couch, trying to take a nap. My phone rang and it was a woman from an ostomy group. I remembered vaguely telling my ostomy nurse that it was okay to be contacted by this support group. I always say yes to stuff like that because I figure it can’t hurt.

The woman on the other end was very sweet. She asked if I was upset. I told her I wasn’t. She was gentle, but she persisted. She didn’t believe me.

“No, I really just want to be able to shit,” I told her, laying my arm over my eyes to block out the sun. “Honestly, I’m a lot more afraid of the damage from my mast cell disease if I don’t get this out than I am of shitting into a bag.” She was quiet for a while. “What?” I asked.

“Nothing, it’s just….You really aren’t upset,” she said finally.

“No, I’m really not,” I answered. And I wasn’t.

She offered me her many good tips on how to hide your ostomy bag. She clearly cared a lot (and felt badly – I was the youngest person her group had worked with) so I listened. She talked about girdles and pregnancy bands and tank tops and belt things with pouches and bathing suits. It was interesting, in a sort of voyeuristic way. I thought about her when I went swimming a couple of months later. My preparation consisted of putting on my normal two piece bathing suit and going in the pool. I didn’t see any reason to hide it. I wasn’t ashamed of it.

When I found out I was getting a PICC line, several people asked me how I would cover it. “With an occlusive dressing,” I answered automatically every time.

“No, like so people won’t be uncomfortable,” they sometimes followed up.

“It’s not my problem if they’re uncomfortable,” I said with increasing irritation every time I responded. “It’s not my fault I need the line.”

Someone asked me how I covered my port a few days after I got it. “I don’t.,” I said, thoroughly tired of this line of questioning. “It’s just not who I am.”

Modifying my body doesn’t upset me, even in the ways I just described. My hair has been in turns purple, blue, red, pink and red again. I had numerous piercings, all over my body, until once, after a surgery, when I just didn’t want to put the jewelry back in. It didn’t feel right anymore.

I am sure to many people, it must seem like my disease doesn’t upset me. That’s not the case. My relative resignation about the state of my illness is a survival mechanism. It looks a lot like not caring sometimes, but that’s not what it is. The pain shows, but it’s harder to see if you’re not watching carefully. It shows in the moments when I am unable to find even a shred of dignity.

Monday morning, I started anaphylaxing at work. I had a little bit of a cold and was overtired and sore and generally sort of walking the line anyway. I walked up to the nurse’s office and gave myself IV meds while she took my blood pressure. “It’s 88/60,” she told me with wide eyes. I didn’t want to epi at work because then they would have to call an ambulance. I knew the IV Benadryl and steroids would keep me stable for a bit so I called my mother. At the age of 30, I called my mother to come get me at work because I was too sick to get home safely. The nurse emailed my boss to tell him I went home sick, which was for some reason a lot more mortifying than it should have been. My father and cousin had to go pick up my car later. It was embarrassing.  It felt undignified.

Then, later on that night, my dog threw up. I completely lost it. I throw up most days, often multiple times. If it doesn’t all get into its intended receptacle, I just clean it up. No big deal. But these last few weeks have been grosser than usual as pertains to my GI tract and I am so sick of cleaning up shit. I couldn’t deal with it. I just hit a limit of grossness and indignity in my life sometimes and it’s like I can feel my self worth just leeching away from my soul into the air around me.  It’s a perception thing and it’s so individual.  I know how strange it is to some people that I don’t mind being transparent about my life, the external signs of my internal illness visible to the world, but sometimes am upset about needing help.  I know people think it’s strange.  But it’s not my problem, and it’s not my responsibility to behave in a way that makes people comfortable with my illness.

Someone posted this week about a “friend” who was upset that they joked about their illness. My response was something like, “That guy’s an asshat, it’s not your job to act how he thinks sick people should act.” And it’s not. I don’t keep my central lines uncovered because it makes some statement about illness. I keep them uncovered because I genuinely can’t be bothered. It’s just not who I am to care.

But I care about my disease, and I care about the life I can’t have because of it, and sometimes, it’s too much. Some days I am tired of cleaning up vomit and emptying bags of my own waste and cleaning blood stains out of my clothes. Do not mistake my resoluteness for apathy.

This ability to move forward, to not be upset about mundane things – it is a learned skill, not a natural acceptance of the terrible reality of chronic disease. We are just trying to find grace in life. We are just hoping to navigate through the rough pockets with some autonomy and a little bit of dignity.

 

Artifact

I have spent a lot of my professional life using microscopes. There is this rhythm you get into, when you do it a lot; lifting the edge of the slide out of the book with a gloved fingernail, pulling back the guard to slide the glass into place, spinning the fine adjustment back and forth with your fingertips. Sitting taller to look through the eyepiece into the tiny world below. Looking closely to see the ways you may have changed it.

The process of putting a sample on a slide and staining it can change it, sometimes even if you’re careful. Things look desiccated if you dry them too fast; elongated and distorted if you compress the sample. The dye sits heavy in some places and doesn’t wash off completely. When I look at a slide, I’m not looking at a sample. I’m looking at a sample that I changed in some way. These changes can be misread if not careful, because once I make them, they blend right into that tiny world. They are artifacts of my actions, some damage left behind by the process of being examined.

I spent most of last week in bed. My GI tract felt like I had swallowed lava. I had abdominal neuropathy that felt like electrical shocks spiderwebbing out from just below my xiphoid process. I was tired, weak and foggy from the anesthesia. I slept a lot and watched Netflix and did work from the relative comfort of my bed. These symptoms are not really so much from masto so much as they are from the procedure. Anytime I have a procedure, anytime I take medication, anytime I change my life to accommodate my disease. It leaves a lasting change not from the disease itself, but from the treatment of it.  It leaves an artifact.

I have had several surgeries. I have had hundreds of imaging tests. I have had so many scopes I literally don’t know how many scopes I have had. Every day I take handfuls of pills, infusions, injections, push meds.   This week I am acutely aware of the damage I have sustained by virtue of being treated for my disease. My mast cell medications bring my already slow GI tract to a dead halt. But of course the alternative is that I don’t treat my disease – and of course that’s worse. Right? It’s worse, right?

I know it is worse. I know that I will never live safely without meds. I in no way mean to imply that I am stopping treatment. It’s just getting really hard to know what is from my disease and what is from the treatment. It’s getting hard to know all the ways I have been altered by the experience of living with mast cell disease.

I feel more and more the toll this constant need for medical care is taking on me. With my accessed port, my surgical scars, my ostomy,  I myself am becoming increasingly damaged by this process. I am becoming an artifact.

Fragrance allergy

Public understanding of allergy pathology is often inaccurate and can create dangerous misunderstandings. The most common is that you must ingest a protein in order to have an anaphylactic reaction. Another is that inhalation or skin contact cannot cause severe reactions.

Both of these are inaccurate, especially, but not only, for people with mast cell disease. People without mast cell disease have severe reactions to IV contrast without having allergy antibodies to the protein (Singh, 2008). Inhalation can cause anaphylaxis. There are even cases of patients who can tolerate ingestion of a food but not inhalation, such as seen in Baker’s asthma, the second highest cause of occupational asthma in the UK (Ramirez, 2009). While ingestion of protein is the most common mechanism for severe allergic reactions, it is certainly not the only one.

Fragrance allergy is a growing problem worldwide. Fragrance is now one of the top five allergens in North American and European countries and can cause skin, eye and respiratory problems (Jansson, 2001). At least 100 chemicals commonly used in fragrances can cause contact allergies when applied to skin, even passively (Johansen, 2003). European Commission’s Scientific Committee on Cosmetic Products and Non-Food Products’ 1999 list of allergenic substances contained 24 chemicals and 2 botanical preparations, all used as scents (European Parliament and Council Directive 2003/15/EC, 2003).

Though the exact mechanism is not clear, perfume is known to cause asthma and other respiratory problems (Elberling J, 2009). A Dutch study found that isoeugenol, a common component of fragrances, can cause increased proliferation of cells in respiratory tract lymph nodes when inhaled (Ezendam J, 2007). However, more research is needed in this area.

A significant portion of the population also reports adverse reactions to scented products in general, even when worn by others. Products like scent lotions, perfumes, soaps and air fresheners are all cited as problematic. A 2009 paper reported on the results of two surveys of over 1000 people. 30.5% of the general population found scented products on other people to be irritating. 19% reported health effects from air fresheners, and 10.9% reported the venting of scented laundry products as causing symptoms. Percentages were higher among asthma patients and those with chemical sensitivity (Caress SM, 2009).

Symptoms reported from exposure to fragrances on others includes: headaches, chest tightness, wheezing, diarrhea, vomiting, mucosal irritation, reduced pulmonary function, asthma, asthmatic exacerbation, rhinitis, irritation of the airway, nose and mouth, and dermatitis (Caress SM, 2009).

Many of you are aware of the recent dispute over whether or not essential oils can be dangerous. They can. Even in the absence of known chemical triggers, the oils themselves can be triggering to many. As an example, clove oil, which has a large eugenol component, has been tied to severe allergic reactions (A.O. Nwaopara, 2008). Oils of citrus fruits are known to liberate histamine and make it more available to cause mast cell symptoms (Novak, 2007). Furthermore, while the reaction profile of each mast cell patient is unique, the hallmark of mast cell disease is anaphylactic reactions to seemingly harmless substances. Mast cell patients are increasingly being viewed as “canaries in the coal mine” for their ability to detect minute quantities of offensive components. While mastocytosis is rare, affecting about 0.3-13/100000 patients, some level of mast cell activation syndrome (MCAS) is thought to affect a much larger percentage of the population, in the neighborhood of 5% (Molderings, 2014).

Fragrances, from essential oil or otherwise, can cause contact allergies, headaches and respiratory symptoms. In mast cell patients, scents can cause severe full body reactions that are potentially life threatening or fatal.

MCAS: Pain

Pain is an unfortunate fact of life with MCAS. Muscle fatigue and weakness are common complaints, but myositis and rhabdomyolysis are rare. Some patients have elevated creatine kinase and/or aldolase, but have no related symptoms.

Bone pain is frequently reported with MCAS. Osteopenia and osteoporosis are common findings. Focal osteosclerosis is also sometimes found, but less frequently. Joints are often painful, which can lead to diagnoses of osteoarthritis, seronegative rheumatoid arthritis, fibromyalgia and polymyalgia rheumatica. Pain can migrate and is often poorly localized. Patients often feel pain in joints, bones and soft tissues, sometimes inconsistently.

Mast cells have been implicated in several pain disorders. Chronic lower back pain has been hypothesized to be related to mast cell activation for over a decade. Complex regional pain syndrome Type I, formerly known as reflex sympathetic dystrophy (RSD) and reflex neurovascular dystrophy (RND), is the most painful long term condition described. It is marked by neurogenic inflammation (nervous system swelling), sensitization of pain receptors and circulatory problems that cause swelling and color changes. It can affect any part of the body. Mast cells have been linked to the inflammatory response seen in CRPS patients.

Neurons with noradrenaline, serotonin and opioidergic receptors inhibit transmission of pain signals. (This is why taking opiates works for pain – it binds to these opioidergic receptors and suppresses the pain signals.) In the spinal cord, pain signals from the peripheral pathways meet up with the spinal pain signals to send to the brain. Here is where molecules like GABA, opioids made in the body and serotonin control pain transmission.

In chronic pain, serotonin acts to amplify the peripheral pain signals instead of suppress them. Increased serotonin levels and mast cell counts are found in many patients with chronic abdominal pain. About 95% of serotonin in the body is found in the peritoneal cavity, which explains the chronic pain many people feel in this region. Mediators released from colon biopsies in IBS patients were proven to excite the local nerves and activate pain receptors. Serotonin is one of these mediators.

Some antidepressants are known to affect serotonin secretion from mast cells. In particular, tricyclic antidepressants inhibit serotonin release in a dose dependent manner at higher concentrations. Clomipramine was seen to be the most effective, with amitriptyline and doxepin inhibiting release of serotonin and histamine at higher doses. All three were found to affect both uptake and reuptake of serotonin by mast cells and therefore lowering the relative concentration of serotonin in the local environment.

MCAS pain is often difficult to treat with typical pain medications. Antihistamines and cromolyn should be used to manage pain where possible. For bone related pain, bisphosphonates are usually effective. There is some data to suggest hydroxyurea can help manage pain in MCAS patients.

 

References:

Xinning Li, MD; Keith Kenter, MD; Ashley Newman, BS; Stephen O’Brien, MD, MBA. Allergy/ Hypersensitivity Reactions as a Predisposing Factor to Complex Regional Pain Syndrome I in Orthopedic Patients. Orthopedics 2014: Volume 37 · Issue 3: e286-e291

Giovanni Barbara, et al. Mast Cell-Dependent Excitation of Visceral-Nociceptive Sensory Neurons in Irritable Bowel Syndrome. Gastroenterology Volume 132, Issue 1, January 2007, Pages 26–37.

Ferjan, F. Erjavec . Changes in histamine and serotonin secretion from rat peritoneal mast cells caused by antidepressants. Inflammation Research 1996, Volume 45, Issue 3, pp 141-144.

Barbara, V. Stanghellini, R. De Giorgio et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology, vol. 126, no. 3, pp. 693–702, 2004.

Barbara, B. Wang, V. Stanghellini et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology, vol. 132, no. 1, pp. 26–37, 2007.

Afrin, Lawrence B. Diagnosis, presentation and management of mast cell activation syndrome. 2013. Mast cells.

Language matters: Mast cell terminology

This is by no means a comprehensive list – just a review on definitions of some commonly confused terms.

Acute: This word gets used a lot when people mean “severe.” Acute does not mean severe. It means sudden onset or having a short, limited course. For example, stage III anaphylaxis is an acute complication of mast cell disease. Its symptoms come on suddenly, require immediate treatment, and once treated, resolves. (I am not referring to the after effects of anaphylaxis – just the emergency and treatment.) In a medical sense, acute is the opposite of chronic.

Chronic: Long term, occurs all the time, is expected to occur forever. I have mast cell disease and am chronically ill. I have acute anaphylactic emergencies.

Progressive: Getting worse or will get worse. This term gets used loosely by patients to mean that their symptoms get worse. Medically speaking, this generally refers to progression of disease from one stage to the next, like SM to ASM. SM and MCAS are not inherently progressive diseases. People who have progressed from SM to SSM or ASM have progressive disease.

 

Systemic symptoms: Any symptoms that do not involve the skin. Can be present in cutaneous mastocytosis or MCAS. So diarrhea is a systemic symptom. Tachycardia is a systemic symptom. Systemic symptoms do not mean you have SM.

Systemic mastocytosis: the diagnosis you receive if you meet either the major criterion listed subsequently and at least 1 of the 4 minor criteria, or at least 3 minor criteria if the major criterion is not met:

Major criterion

Multifocal, dense infiltrates of mast cells (≥15 mast cells in aggregates) detected in sections of bone marrow and/or other extracutaneous organ(s)

Minor criteria

In biopsy sections of bone marrow or other extracutaneous organs, >25% of the mast cells in the infiltrate are spindle-shaped or have atypical morphology, or, of all mast cells in bone marrow aspirate smears, >25% are immature or atypical

Detection of an activating point mutation at codon 816 of KIT in bone marrow, blood, or other extracutaneous organ

Mast cells in bone marrow, blood, or other extracutaneous organ express CD2 and/or CD25 in addition to normal mast cell markers

Serum total tryptase persistently exceeds 20 ng/mL (unless there is an associated clonal myeloid disorder, in which case this parameter is not valid)

The diagnosis of SM is unrelated to the symptoms the patient experiences. Some SM patients have no symptoms. Some have severe symptoms.

Systemic symptoms ≠ systemic disease (SM)

 

Aggressive symptoms: Frequent or severe symptoms, which may be life threatening.

Aggressive disease: Doctors sometimes use this term to mean a quick progression of symptoms or rapid change in quality of life.

Aggressive systemic mastocytosis: A diagnosis that indicates multiple organ infiltration and damage by mast cells. Lifespan is significantly shortened in many patients. It is diagnosed by already meeting the criteria for SM and then also having at least one C finding, listed here:

Bone marrow dysfunction manifested by one or more cytopenia (ANC < 1.0 × 109/l, Hb < 10 g/dl, or platelets < 100 × 109/l), but no frank non-mast cell haematopoietic malignancy

Palpable hepatomegaly with impairment of liver function, ascites and/or portal hypertension

Skeletal involvement with large-sized osteolysis and/or pathological fract

Palpable splenomegaly with hypersplenism

Malabsorption with weight loss due to GI mast cell infiltrates

Aggressive symptoms and aggressive disease ≠ aggressive systemic mastocytosis (ASM)

 

Smoldering systemic mastocytosis (SSM): A progression from SM with markers that indicate likelihood of developing ASM. Diagnosed if two or more of the following B findings are present with previous diagnosis of SM:

Bone marrow biopsy showing > 30% infiltration by mast cells (focal, dense aggregates) and/or

serum total tryptase level > 200 ng/ml

 

Signs of dysplasia or myeloproliferaion in non-mast cell lineage, but insufficient criteria

for definitive diagnosis of a haematopoietic neoplasm by WHO, with normal or only slightly

abnormal blood counts

 

Hepatomegaly without impairment of liver function, and/or palpable splenomegaly without

hypersplenism, and/or palpable or visceral lymphadenopathy

 

MCAS: Differing criteria among experts

What criteria you have to meet to be diagnosed with MCAS depends on which doctor you see – even the experts don’t agree.

Molderings, Afrin 2011 Akin, Valent, Metcalfe 2010 Valent, Akin, Castells, Escribano, Metcalfe et al 2012
MCAD (umbrella term including both MCAS and SM) diagnosed if both major criteria, or one major criterion and one minor criterion, are present; following bone marrow biopsy, diagnosis is narrowed down to either SM or MCAS MCAS diagnosed if all criteria are met MCAS diagnosed if all criteria are met

Major Criteria

Multifocal of disseminated dense infiltrates of mast cells in bone marrow biopsies and/or in sections of other extracutaneous organ(s) (GI tract biopsies; CD117-, tryptase- and CD25- stained)
Episodic symptoms consistent with mast cell mediator release affecting ≥2 organ systems evidenced as follows:
  1. Skin: urticaria, angioedema, flushing
  2. Gastrointestinal: nausea, vomiting, diarrhea, abdominal cramping
  3. Cardiovascular: hypotensive syncope or near syncope, tachycardia
  4. Respiratory: wheezing
  5. Naso-ocular: conjunctival injection, pruritus, nasal stuffiness
Typical clinical symptoms
Unique constellation of clinical complaints as a result of a pathologically increased mast cell activity (mast cell mediator release symptom) A decrease in the frequency or severity or resolution of symptoms with antimediator therapy: H1– and H2-histamine receptor inverse agonists, antileukotriene medications (cysteinyl leukotriene receptor blockers or 5-lipoxygenase inhibitor), or mast cell stabilizers (cromolyn sodium) Increase in serum total tryptase by at least 20% above baseline plus 2 ng/ml during or within 4 h after a symptomatic period
  Evidence of an increase in a validated urinary or serum marker of mast cell activation: documentation of an increase of the marker to greater than the patient’s baseline value during a symptomatic period on ≥2 occasions or, if baseline tryptase levels are persistently >15 ng, documentation of an increase of the tryptase level above baseline value on 1 occasion. Total serum tryptase level is recommended as the marker of choice; less specific (also from basophils) are 24-hour urine histamine metabolites or PGD2 or its metabolite 11-β-prostaglandin F2. Response of clinical symptoms to histamine receptor blockers or MC-targeting agents e.g. cromolyn
  Rule out primary and secondary causes of mast cell activation and well-defined clinical idiopathic entities

Minor Criteria

Mast cells in bone marrow or other extracutaneous organ(s) show an abnormal morphology (>25%) in bone marrow smears or in histologies
Mast cells in bone marrow express CD2 and/or CD25
Detection of genetic changes in mast cells from blood, bone marrow or extracutaneous organs for which an impact on the state of activity of affected mast cells in terms of an increased activity has been proved
Evidence of a pathologically increased release of mast cell mediators by determination of the content of:

  1. Tryptase in blood
  2. N-methylhistamine in urine
  3. Heparin in blood
  4. Chromogranin A in blood
  5. Other mast cell specific mediators (leukotrienes, PGD2)

MCAS: GI Symptoms and Liver Abnormalities

MCAS patients suffer a variety of GI ailments, which are largely in common with SM.

Aerophagia, excessive swallowing of air, is very common. It is not entirely obvious why this occurs. In other patient populations, aerophagia is usually due to poor coordination between swallowing and respiration. Severe cases can lead to abdominal distention, aspiration of stomach contents into the lungs and esophageal rupture.

Chest discomfort is common in MCAS. Cardiac issues should be ruled out, but in most people, it is due to esophagitis. Some patients have a previous diagnosis of reflux but it is refractory to all relevant treatments.

Diarrhea and constipation, sometimes alternative, are very common. In one study, 89% of MCAS patients studied had frequent nausea, 100% had abdominal pain of some nature, and 69% had noncardiac chest pain. Partial bowel obstructions are uncommon, but do occur in MCAS. They are thought to be due to focal dysmotility or focal edema.

IBS is a frequent previous diagnosis in MCAS. The GI tract often looks normal by eye and typical H&E staining shows mild inflammation. Staining for mast cells often shows they are increased. Of note, there is not a universal consensus on what is considered “increased mast cells” in GI samples. Generally, above 20 cells per hpf is marked as high by pathologists. Presence of the D816V CKIT mutation is rare in GI biopsies of MCAS patients.

Selective malabsorption of certain nutrients is often seen in MCAS. Iron malabsorption is by far the most common. Copper and B vitamins are often poorly absorbed as well. Protein calorie malabsorption is rare, but leads to weight loss and wasting.

Pancreatic enzyme supplementation can be helpful in treatment of diarrhea, weight loss and malabsorption. The fact that this often works suggests that MCAS driven inflammation or fibrosis causes pancreatic exocrine deficiency, a condition in which the pancreas does not make enough digestive enzymes. Mast cells have a known link to painful chronic pancreatitis. In patients with painful vs painless chronic pancreatitis, mast cell density is 3.5X higher in pancreas biopsy.

About half of MCAS patients have some kind of liver abnormality. Fibrosis (obliterative portal venopathy) is the most common. However, fatty metamorphosis, sinusoidal dilatation, venoocclusive dilatation, nodular regenerative hyperplasia and cirrhosis have also been seen. Sterile (non-infectious) inflammation of the liver and portal trial infiltration by lymphocytes and eosinophils has also been identified in a number of patients. In particular, these patients often have a 2-3X elevation in transaminases and/or alkaline phosphatase, determinants of liver function. Impeded flow of bile from the liver is usually absent. Portal hypertension is unusual but has occurred, causing swelling of the spleen and varices in the esophagus. Rarely, free fluid in the abdomen (ascites) has occurred in MCAS patients.

One study found that 75% of MCAS patients tested had high cholesterol levels. Importantly, 79% of patients had “normal” BMI or were underweight, so the high cholesterol was not correlated to weight. 44% had a twofold or greater elevation of liver enzymes. 36% had increased bilirubin in the blood. 15% had fatty liver; 13% had swelling of the liver; 4% had cysts; 4% had adenomas; 2% had hemangiomas. 14% of patients had pancreatic involvement with elevated lipase or amylase.

 

References:

Kirsten Alfter, Ivar von Ku gelgen, Britta Haenisch, Thomas Frieling, Alexandra Hu lsdonk, Ulrike Haars, Arndt Rolfs, Gerhard Noe, Ulrich W. Kolck, Jurgen Homann and Gerhard J. Molderings. New aspects of liver abnormalities as part of the systemic mast cell activation syndrome. 2009 Liver International 29(2): 181-186.

Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome. 2011. Mast Cells.