Diabetes, mast cells and allergic disease

Patients with either type I or II diabetes mellitus demonstrate unusual physiology pertaining to hypersensitivity and mast cell activation. This was first described in 1962, when a paper reported that diabetic animals do not experience anaphylactic shock.   Despite the amount of time that has passed, the reasons for this are still being unraveled.

The role of mast cells in type II diabetes mellitus is more straightforward. When mice are made obese through dietary manipulation, they normally develop glucose intolerance or insulin resistance. If the mice are mast cell deficient, they do not develop these conditions. Transfer of mast cells to mast cel deficient mice was shown to reverse this protection against these complications.

In mice without established type Ii diabetes that were given manipulated diets to induce obesity, treatment with mast cell stabilizers actually prevented the development of type II diabetes. In mice with pre-established type II diabetes, treatment with mast cell stabilizers cromolyn or ketotifen protected against glucose intolerance and insulin resistance. These findings have been replicated in at least one patient, a type II diabetic who had normalized plasma glucose and A1C after six months on cromolyn.

The relationship between mast cells and type I diabetes is far more intricate.   This is mostly understood through a diabetic rat model. It is possible to induce type I diabetes in rats by administering a chemical called alloxan. Triggering diabetes in this way causes a variety of mast cell changes in these animals. The same changes can be seen when causing diabetes via administration of another chemical, streptozotocin.

Diabetic rats have less vascular response to the action of histamine and reduced mast cell degranulation. These animals are resistant to both local and systemic allergic responses, including anaphylaxis.   Mast cell populations become depleted and less likely to activate. When exposed to antigen, diabetic rats have 50% less degranulated mast cells and histamine release compared to non-diabetic controls.

IgE production is also suppressed in diabetic rats, both antigen specific IgE and total IgE. If you transfer mast cells from the spleen and lymph nodes of non-diabetic rats to diabetic rats, IgE production is diminished. Likewise, if mast cells from diabetic rats are transferred into non-diabetic animals, IgE production is restored.

This protection from allergic processes is well established in animals, but also translates to humans. Children with type I diabetes, and their siblings, are less likely to develop asthma. The incidence of bronchial asthma, rhinitis, and atopic dermatitis is lower than predicted in patients with diabetes mellitus.   Risk of death due to anaphylactic shock is significantly reduced in diabetes. This has been attributed to both the depletion of mast cell populations in diabetics, but also to the overproduction of corticosteroids in the body.

 

References:

Carvalho V.F., Barreto E.O., Diaz B.L. et al. (2003) Systemic anaphylaxis is prevented in alloxan-diabetic rats by a mechanism dependent on glucocorticoids. Eur. J. Pharmacol. 472, 221–227.

Carvalho V.F., Barreto E.O., Cordeiro R.S. et al. (2005) Mast cell changes in experimental diabetes: focus on attenuation of allergic events. Mem. Inst. Oswaldo Cruz 100(Suppl. 1), 121–125.

Foreman JC, Jordan CC, Piotrowski W. Interaction of neurotensin with the substance P receptor mediating histamine release from rat mast cells and the flare in human skin. Br J Pharmacol. 1982 Nov;77(3):531-9.

Meng, Fanyin, et al. Regulation of the Histamine/VEGF Axis by miR-125b during Cholestatic Liver Injury in Mice. The American Journal of Pathology, Volume 184, Issue 3, March 2014, Pages 662–673

Theoharides, T., et al. A probable case report of stress-induced anaphylaxis. Ann Allergy Asthma Immunol xxx (2013) 1e2

Kjaer A, et al. Insulin/hypoglycemia-induced adrenocorticotropin and beta-endorphin release: involvement of hypothalamic histaminergic neurons. Endocrinology. 1993 May;132(5):2213-20.

Carvalho V.F, et al. Reduced expression of IL-3 mediates intestinal mast cell depletion in diabetic rats: role of insulin and glucocorticoid hormones. Int. J. Exp. Path. (2009), 90, 148–155.

Carvalho V.F, et al. Suppression of Allergic Inflammatory Response in the Skin of Alloxan-Diabetic Rats: Relationship with Reduced Local Mast Cell Numbers. Int Arch Allergy Immunol 2008;147:246–254.

Carvalho VF, Barreto EO, Diaz BL, Serra MF, Azevedo V, Cordeiro RS, et al: Systemic anaphylaxis is prevented in alloxan-diabetic rats by a mechanism dependent on glucocorticoids. Eur J Pharmacol 2003; 472: 221–227.

S.C. Cavalher-Machado, et al. Down-regulation of mast cell activation and airway reactivity in diabetic rats: role of insulin. Eur Respir J 2004; 24: 552–558.

 

Questions on bone involvement

I wrote these posts in direct response to an email I received from a person in the MastAttack Facebook group (feel free to join) who follows the blog. This person had the following questions:

1) Are osteosclerotic lesions the same as/affiliated with the terms sclerotic, blastic and osteoblast?

Lisa’s response: Sclerotic is associated with the term osteosclerotic. Osteosclerotic means “bone hardening”. Sclerotic can also be used to describe other pathologies, like dermatosclerotic.

Blastic is associated with the term osteoblast, but it can also mean several other cell types. One example of the word “blast” is to mean an immature blood cell. In this context, high levels of blasts can mean severe infection or blood cancers. Osteoblast is the cell type that makes new bone. So osteosclerosis is thought to occur because osteoblasts work faster at laying down new bone than osteoclasts work at eating up old bone.

2) Are osteolytic lesions the same as/affiliated with the terms lytic and osteoclast?

Lisa’s response: Lytic is associated with the term osteolytic. Lytic is the adjective form of lysis, which means to rupture. Osteolysis is caused by two distinct processes occurring together: the first is that rapid growth of abnormal cells (like neoplastic mast cells) inhibits the action of osteoblasts, which normally lay down new bone; and the second is that osteoclast activity is increased, so bone is being absorbed very quickly.

3) If above correlations are correct, A&C below seem contradictory to me, as do B&D.??? Perhaps I’m confused when I isolate it out of context (it was conversation where you were clarifying for someone that osteoporosis wasn’t criteria for SM). (Lisa’s note: Statements A, B, C and D are below these questions for reference.)

Lisa’s response: In multiple studies, patients with ISM, SSM, ASM and SM-AHNMD have been identified as having osteosclerosis. In the largest study (Barete 2010), they found osteosclerosis was more closely associated with aggressive forms of SM (SM-AHNMD and ASM). However, they are still only talking about four people in the aggressive group as opposed to two people in the other (ISM/SSM) group. So in that study, more people with aggressive disease had osteosclerosis than those who had less aggressive disease. In another study, there was no correlation found between osteosclerosis and disease severity.

In particular, what we do not know is whether or not osteosclerosis makes progression more likely by itself. The most robust study found that osteosclerosis in conjunction with swelling of the liver and spleen, presence of multilineage KIT mutation and high increase of baseline serum tryptase warranted careful monitoring for progression. So I’m not convinced that osteosclerosis as a standalone marker is immediately concerning regarding progression, but taken along with these other factors, it may be an indication for cytoreductive therapy.

4) Ultimately, I’m trying to get straight in my mind which is the “worse” lesion (or maybe it’s apples/oranges?) as it pertains to potential progression to an advanced SM category.

Lisa’s response: As pertains to mast cell pathology, large osteolytic lesions are considered the “worst” in that they immediately put you in the ASM category. Again, the only other way this happens is if you have multiple bone breaks as a result of severe osteoporosis (in which osteoporosis is not the qualifier, but the breaks).

So I would consider osteosclerosis as being less severe than osteolytic lesions for the specific purpose of staging SM. However, osteosclerosis is associated with some additional clinical considerations, like blood count abnormalities and higher tryptase, so that should be monitored carefully. Ultimately, this is an issue of research focusing – we need enough time to identify ISM, SSM, ASM and SM-AHNMD patients with osteosclerosis, osteoporosis and osteolysis and determine whether or not osteosclerosis by itself is a determinant of disease progression.

 

Statements:

Note: Both A and B are comments I made as part of a larger FB thread regarding what constitutes “bone involvement” as a diagnostic criterion in staging of SM.

A) Lisa Klimas Osteosclerotic lesions are not immediately a red flag in SM, and about half of SM patients have bone involvement. I wrote a couple of in depth posts about bone manifestations of SM that you may find helpful. I can’t cut and paste in comments on FB for some reason, but google “mastattack bone manifestations of sm” and it comes right up. It’s a two part series.

Lisa’s Response: This was part of a conversation about what constitutes “bone involvement” as a diagnostic marker in staging of SM. It is possible to have ISM or SSM and have osteosclerotic lesions. It does not immediately move you into ASM territory. My phrasing here was poor in that I used bone involvement very broadly (meaning anything involving your bones rather than just the types that affect staging), so that is my fault in that it was confusing.

B) Lisa Klimas Skeletal involvement as applies to mast cell disease means osteolytic lesions, which is a marker for ASM ONLY when you meet the criteria for SM already.

Lisa’s Response: This was part of that same conversation, in which we were discussing bone lesions. One of the markers that qualifies a person as having ASM as opposed to ISM is “bone involvement,” which is defined as large osteolytic lesions or successive fractures due to severe osteoporosis. Here, I was discussing lesions, which is why I omitted the successive fractures. As explained in the earlier part of this post, the osteoporosis does not qualify as “bone involvement” as criteria for ASM – it is the successive fractures.

C) Osteosclerosis is more closely associated with aggressive forms of SM.

Lisa’s Response: This was in reference to the Barete 2010 paper.

D) (I know these are older articles): “The severity of bone lesions on x-ray correlate with urinary histamine levels. Lytic lesions, which are the predominant finding, have been associated with moderate increases in bone marrow mast cells. Significantly more mast cell infiltration has been correlated with sclerotic ”

Reference: Jianguo Tao, Keith Flaherty and Adam Bagg. Unusual Hematologic Malignancies. Case 1. Hematologic Malignancy Presenting With Diarrhea and Bony Lesions: Systemic Mastocytosis. Journal of Clinical Oncology, Vol 20, No 17 (September 1), 2002: pp 3737-3744

Lisa’s Response: The paper quoted is from 2002 and the reference for this above statement is from 1992. It involved a patient group of nine people. Criteria for SM/ASM/etc were different then. I am waiting on a hard copy of the 1992 paper referenced and will do a follow up post when I have been able to review the primary source. This is the reference for the 1992 paper:

Reference: de Gennes C, Kuntz D, de Vernejoul MC. Bone mastocytosis. A report of nine cases with a bone histomorphometric study. Clin Orthop Relat Res. 1992 Jun; (279):281-91.

Bone involvement in ISM, SSM, SM-AHNMD and ASM: More literature review (part 3)

A 2009 paper looked at prognosis of 157 ISM patients (Escribano 2009). 27% had bone involvement, with 18% patients having osteoporosis, 6% having diffuse bone sclerosis, 4% having patchy bone sclerosis 2% having small osteolysis and 3% having pathological fracture.

A 2012 paper (van der Veer 2012) assessed the frequency of osteoporosis and osteoporotic fractures in a group of 157 ISM patients. They found 28% had osteoporosis, with 27% having osteoporosis of the lumbar spine and 1% having osteoporosis of the hip. 4% had evidence of osteosclerosis.

43% of patients under 50 years old had had at least one fracture (osteoporotic or not) and 61% of patients over 50 years old had had at least one fracture. 27% of patients had one or more vertebral fractures and 21% had non-vertebral, osteoporotic fractures. 23% of male patients under 50 had osteoporosis as well as 38% over 50. 12% of women under 50 had osteoporosis as well as 33% over 50. In total, 37% had osteoporotic fractures. In the group with comorbidities that might cause osteoporosis or fractures, 49% had osteoporotic fractures and 37% had osteoporosis. 59% ISM patients without UP had osteoporotic fractures compared to 28% with UP.

A 2013 paper (Matito 2013) looked at the association of baseline serum tryptase with disease features, including progression to SSM or ASM. 74 patients with ISM were included in the study and were followed for at least 48 months. None of them received cytoreductive therapy. Patients with an increased serum baseline tryptase slope and those without significant tryptase increase had similar prevalence of osteoporosis, patchy bone sclerosis and diffuse bone sclerosis at both presentation and end of study. However, the group with increased serum baseline tryptase was more likely to develop diffuse bone sclerosis in the time span between the beginning of the study and the end of the study (13% vs 2% without significant tryptase increase).

Among the group with low serum baseline tryptase increase, 9% had osteoporosis at the start, and 14% at the end; 5% had patchy osteosclerosis at the end; 2% had diffuse bone sclerosis at the end. None in this group progressed to SSM or ASM.

Among the group with high serum baseline tryptase increase, 10% had osteoporosis at the start, and 16% at the end; 6% had patchy osteosclerosis at the end; 13% had diffuse bone sclerosis at the end. 13% progressed to SSM and 6% to ASM.

Four patients in this study progressed to SSM after the start of the study, in a time ranging from 8-85 months. All had serum baseline tryptase of at least 200 ng/ml and had increased serum baseline tryptase slope. They also had D816V CKIT mutation in cells other than mast cells. Two of these patients progressed to ASM. Both of these patients had diffuse bone sclerosis and swelling of both the liver and spleen. The authors of this paper recommend special attention to the development of hepatomegaly and splenomegaly and diffuse bone sclerosis.

 

References:

Maurizio Rossini, et al. Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49 (2011) 880–885.

Theoharides TC, Boucher W, Spear K. Serum interleukin-6 reflects disease severity and osteoporosis in mastocytosis patients. Int Arch Allergy Immunol 2002;128: 344–50.

Dobigny C, Saffar JL. H1 and H2 histamine receptors modulate osteoclastic resorption by different pathways: evidence obtained by using receptor antagonists in a rat synchronized resorption model. J Cell Physiol. 1997 Oct;173(1):10-8.

Barete S, Assous N, de Gennes C, Granpeix C, Feger F, Palmerini F, et al. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 2010;69:1838–41.

Nicolas Guillaume, et al. Bone Complications of Mastocytosis: A Link between Clinical and Biological Characteristics. The American Journal of Medicine (2013) 126, 75.e1-75.e7

van der Veer, W. van der Goot, J. G. R. de Monchy, H. C. Kluin-Nelemans & J. J. van Doormaal. High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 67 (2012) 431–438.

Kushnir-Sukhov NM, Brittain E, Reynolds JC, Akin C, Metcalfe DD. Elevated tryptase levels are associated with greater bone density in a cohort of patients with mastocytosis. Int Arch Allergy Immunol. 2006;139(3):265-70. Epub 2006 Jan 30.

Matito A, Morgado JM, Álvarez-Twose I, Laura Sánchez-Muñoz, Pedreira CE, et al. (2013) Serum Tryptase Monitoring in Indolent Systemic Mastocytosis: Association with Disease Features and Patient Outcome. PLoS ONE 8(10): e76116. doi:10.1371/journal.pone.0076116

Escribano L, A lvarez-Twose I, Sanchez-Munoz L, Garcia-Montero A, Nunez R, Almeida J et al. Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish network on mastocytosis in a series of 145 patients. J Allergy Clin Immunol 2009;124:514–521.

Bone involvement in SM (ISM, SSM, SM-AHNMD, ASM): Literature review (part 2)

There have been several publications on bone involvement in SM. Importantly, not all of these papers define SM the same way. Some define it as ISM, while others define it as ISM, SSM, SM-AHNMD and ASM. (I personally am sloppy about not specifying when I mean ISM versus when I mean any all the systemic proliferative groups. So if it’s not clear, please ask.) Another thing to be aware of is that the terminology for osteosclerosis is not consistent. It is sometimes referred to as osteocondensation (this is primarily a term used by French researchers). I have done some digging recently on this and cannot find any indication that these two terms do not represent the same phenomenon (increased deposition of bone), so if anyone knows of any papers or sources that say they are different, please let me know.

A 2010 paper (Barete 2010) defines SM as ISM, SSM, SM-AHNMD and ASM. They divided the study into two groups: Variant 1 (non-aggressive), ISM and SSM; and Variant 2 (aggressive), SM-AHNMD and ASM.

Overall (ISM, SSM, SM-AHNMD and ASM), 49% of patients had some form of bone involvement. Osteoporosis was most common, occurring in 31% of patients. 17% had a vertebral fracture. 8% had osteosclerosis. 4% had a mixed pattern, so more than one type of bone involvement. 5% had osteopenia with a previous fracture (this could be unrelated to mast cell disease, like an arm broken in a fall). Only one patient had a focal area of osteolysis with spontaneous fracture.

56% of variant 2 (aggressive) group had osteoporosis, compared to 23% of variant 1. However, when they excluded people who were classified as variant 2 based upon bone involvement, the association dropped to 17% variant 2 with osteoporosis and 23% of variant 1. Osteoporosis associated with vertebral fracture affected 48% variant 1 and 8% variant 2. Osteoporosis was also found to be associated with fewer GI symptoms, with 39% variant 1 having GI issues while 65% variant 2 did.

A total of six patients (out of a total group of 75) had osteosclerosis. One ISM, one SSM, three ASM and one SM-AHNMD patient had osteosclerosis. This translates to two in the variant 1 group and four in the variant 2 group, so twice as many in the aggressive group (ASM, SM-AHNMD) as in the non-aggressive group. 66% of patients in variant 2 with osteosclerosis had a blood count abnormality (anemia, thrombocytopenia, eosinophilia) vs 12% in variant 1. 83% of patients in variant 2 with osteosclerosis had received cytoreductive therapy vs 33% in variant 1, and higher tryptase level was associated with osteosclerosis. Overall, this means that osteosclerosis was associated with a more severe disease presentation (a patient with ISM and osteosclerosis may have a blood count abnormality), but this study does not provide any insight as to whether osteosclerosis is a marker associated with progression toward ASM or SM-AHNMD.

A 2011 paper (Guillaume 2011) assessed bone involvement in a group of CM and SM patients. In this study, SM included ISM, ASM and SM-AHNMD. 45 patients were included.  They found one patient with osteolysis, eight with osteocondensation (a form of osteosclerosis), four with a mixed pattern and three with fractures. They found no association between the presence of radiologic lesions (lesions detected by imaging techniques) and severity (here classified as non-aggressive: ISM and CM, and advanced: ASM and SM-AHNMD).

This study also looked at chemical markers used for bone remodeling. They found that markers associated with both bone resorption and bone formation were higher in mastocytosis patients than in the general population. The higher levels were thought to represent increased number of osteoblasts and osteoclasts due to the increase in mast cells. Osteoprotegerin was also higher in mastocytosis patients. This is a protein released by osteoblasts that regulates the activity of osteoclasts. Levels of C-telopeptide were significantly higher in patients with SM-AHNMD or ASM than in patients with ISM or CM.

A 2011 paper (Rossini 2011) investigated the relationship between tryptase and bone turnover markers (bone specific alkaline phosphatase, C-telopeptide, osteocalcin) in ISM patients. A total of 82 patients were enrolled in the study. 36% had bone involvement. 20% had osteoporosis, with 18.7% found in the spine and 2.5% at the hip. Five patients had a history of bone breaks outside of the spine. 27 patients had vertebral fractures. Two patients had osteosclerotic features and also had particularly high tryptase levels. Another study previously reported that high tryptase can be associated with increased bone density (Kushnir-Sukhov 2006).

This study had a large amount of ISM patients without skin lesions (55%). A very important finding of this particular study was that ISM patients without skin lesions are at the same risk for osteoporosis. As lesions are often one of the more identifiable markers of mastocytosis, the author raises the very valid point that osteoporosis may in some people be the only sign of latent ISM.

This paper reported that “diffuse osteosclerosis associated with SM is not a[n] “osteopetrosis-like osteopathy”, as previously reported, but a skeletal disease characterized by increased bone turnover.” This is important, as they have previously been equated for lack of distinction. The author further notes that the “pathophysiology of SM-related osteosclerosis remains obscure, although it is known that MCs can exert a direct stimulatory effect on osteoblast proliferation, recruitment, and activity.”

This study found that bone mineral density and serum tryptase did not correlate with the serum markers of bone turnover. However, it did find that ISM patients with osteosclerosis had higher tryptase and bone turnover markers (bone specific alkaline phosphatase and C-telopeptides of type I collagen) than ISM patients with other types of bone involvement.

(Literature review continued tomorrow)

References:

Maurizio Rossini, et al. Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49 (2011) 880–885.

Theoharides TC, Boucher W, Spear K. Serum interleukin-6 reflects disease severity and osteoporosis in mastocytosis patients. Int Arch Allergy Immunol 2002;128:344–50.

Dobigny C, Saffar JL. H1 and H2 histamine receptors modulate osteoclastic resorption by different pathways: evidence obtained by using receptor antagonists in a rat synchronized resorption model. J Cell Physiol. 1997 Oct;173(1):10-8.

Kushnir-Sukhov NM, Brittain E, Reynolds JC, Akin C, Metcalfe DD. Elevated tryptase levels are associated with greater bone density in a cohort of patients with mastocytosis. Int Arch Allergy Immunol. 2006;139(3):265-70. Epub 2006 Jan 30.

Barete S, Assous N, de Gennes C, Granpeix C, Feger F, Palmerini F, et al. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 2010;69:1838–41.

Nicolas Guillaume, et al. Bone Complications of Mastocytosis: A Link between Clinical and Biological Characteristics. The American Journal of Medicine (2013) 126, 75.e1-75.e7

van der Veer, W. van der Goot, J. G. R. de Monchy, H. C. Kluin-Nelemans & J. J. van Doormaal. High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 67 (2012) 431–438.

Bone involvement in SM (ISM, SSM, SM-AHNMD, ASM): Clarifications (part 1)

One of the more nuanced aspects of mastocytosis is how it affects bone structure. Previously, it was thought that only patients with systemic mastocytosis experienced bone pain, and that bone pain was always a function of increased proliferation in the marrow. This no longer appears to be the case. Some patients with non-proliferative mast cell disease have been found to experience bone pain, likely as a result of mediator activity on the outside of the bone. In particular, histamine can be very irritating to the cells on the outside of the bone.

Generally speaking, bone cells work like this:

Osteoblasts make new bone. Osteoclasts eat away (resorb) at bone so that new bone can be put in that place. When these processes aren’t balanced, you develop bone conditions.

In osteosclerosis, your body is making new bone faster than it can resorbed. In osteoporosis, your body is resorbing bone faster than new bone is made.   In osteolysis, your body is also resorbing bone faster than new bone is made, but to a much larger extent than usually seen in osteoporosis. Both osteoporosis and osteolysis can cause pathologic fractures, meaning that because your bone is weak from osteoporosis or osteolysis, the bone breaks.

Bone involvement in systemic mastocytosis is important because the type of bone involvement present can be used to stage the disease. Specifically, certain types of bone involvement can cause a person with indolent or smouldering systemic mastocytosis to be reclassified as aggressive systemic mastocytosis (ASM). Osteolysis (in which bone is eaten away) is a marker for ASM. If you have ISM or SSM and are found to have a large osteolytic lesion, you now have ASM.

More confusing is the relationship of osteoporosis to ASM. If you have ISM or SSM AND you have osteoporosis AND you have multiple fractures due to the severity of the osteoporosis (known as pathologic fractures), you are classified as having ASM. There is some debate in the community as to whether or not osteoporosis with successive pathologic fractures is a true indication of ASM. However, it is currently included in the diagnostic guidelines, and so if you meet this criteria while also having ISM or SSM, then you are classified as having ASM.

But I want to be very clear about something: the osteoporosis is NOT the factor that classifies someone as having ASM. It is the MULTIPLE FRACTURES as a result of bone disease that classifies someone as having ASM. So if you have SSM and are diagnosed with osteoporosis and have a single vertebral fracture as a result of osteoporosis, you are NOT classified as having ASM. It is easier I think to consider this “bone involvement” criterion of ASM as osteolysis or multiple fractures due to bone deterioration.

SM is well known as a possible risk factor for osteoporosis. This has been attributed by different groups to either infiltration of bone by mast cells or release of mediators, including histamine, heparin and tryptase. IL-6 levels were also shown to be proportional to disease severity and osteoporosis in mastocytosis patients (Theoharides 2002). Histamine regulates bone resorption by osteoclasts via H1 and H2 receptors (Dobigny 1997). In bone biopsies of osteoporotic patients, the number of osteoclasts is sometimes elevated and sometimes normal.

Up next: literature review of studies on bone involvement in ISM, SSM, SM-AHNMD, and ASM.

 

References:

Maurizio Rossini, et al. Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49 (2011) 880–885.

Theoharides TC, Boucher W, Spear K. Serum interleukin-6 reflects disease severity and osteoporosis in mastocytosis patients. Int Arch Allergy Immunol 2002;128: 344–50.

Dobigny C, Saffar JL. H1 and H2 histamine receptors modulate osteoclastic resorption by different pathways: evidence obtained by using receptor antagonists in a rat synchronized resorption model. J Cell Physiol. 1997 Oct;173(1):10-8.

Barete S, Assous N, de Gennes C, Granpeix C, Feger F, Palmerini F, et al. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 2010;69:1838–41.

Nicolas Guillaume, et al. Bone Complications of Mastocytosis: A Link between Clinical and Biological Characteristics. The American Journal of Medicine (2013) 126, 75.e1-75.e7

van der Veer, W. van der Goot, J. G. R. de Monchy, H. C. Kluin-Nelemans & J. J. van Doormaal. High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 67 (2012) 431–438.

Wayward

It is getting to be time to organize my life in anticipation of several weeks of recovery after surgery. I spend a lot of time writing out instructions on how to live my life. When to pay bills. What pills to take. What medical supplies to order. I revise and update crucial documents, slide them into a folder in my filing cabinet. Every important thing about me reduced to some typed words on so many pages.

I can’t be alone for weeks after surgery. The risk of anaphylaxis is too high. One of my best friends took charge of arranging who will stay with me, when and for how long. I have known most of my close friends for the majority of my life. We grew up together, and will grow old together. We have shared so much, all the ebbs and flows of time. And now I’m sick, and we share that.

It is so much to take care of someone like me, with all of my complications. It is something that can only be done out of the most selfless kind of love. When I told my friends that I would need surgery again, they immediately volunteered their time and energy to help me. It is painful to see how readily they offer to be with me during the hardest times of my life.   It makes me feel so much love that I don’t think my heart can take it.

I found some old pictures yesterday, a whole bunch of us in face paint and costumes half a life time ago. It is hard to believe that we were ever so young. It is hard to believe these are the same people who show up over and over to remind me that I am loved. They put me back together, every time.

I have been so fortunate to have people who love me to the point of bending their entire lives to work around the ill fit of my disease. There is no one in the world luckier than me.

When I first got sick, I could never have imagined it would go on so long. I could never have imagined that I would live this way forever. I could never have imagined all the ways I would be made strong by these people.

I didn’t choose this wayward path. But since I am on it, I couldn’t have found a better group of people to travel it with.

Less

The end of February was one of those spectacularly awful periods where it seems like the entire world is conspiring against me. I woke up with sudden, severe back pain so bad that I literally got stranded in the middle of my bed for twenty minutes until the spasms stopped. My dog got into some not safe for dog food and got sick. It was bitterly cold. I felt like I was generally fucking up the lives of those around me just by existing. Not my best work.

In the middle of this, I told everyone about my decision on surgery. A few days later, I realized I could not say colectomy out loud with feeling this profound emptiness. I got the letter confirming my surgery date and pre-op/post-op appointments. I couldn’t even open it. I threw it into my filing cabinet and slid the drawer closed.

I am very strong willed. It’s not always a good thing. I can talk myself into doing anything if I feel strongly enough that it’s the right thing. I can talk myself into ignoring my fear, but sometimes fear serves a purpose. It protects us. It shows us where the line is, and what side we’re supposed to be on.

So I decided to take a little time and explore my fear and figure out its purpose. I didn’t talk about my health in depth or do any research or write about being sick. I focused on all the other parts of my life. I cleaned my apartment and cooked and worked and took care of Astoria. And I thought. I thought a lot about my life and my disease and this surgery and my fear.

When you are chronically ill, you are in a constant struggle to not have less. Less time. Less money. Less health. Less hope. You work so hard to make your life workable and any setback chisels away this richness of your life, takes pieces that you may never get back. That is what I am afraid of. I am afraid of less. I’m afraid that this will all backfire. I’m afraid that I should live with this pain and poor function. Because I know the space I have with this life, and if I make the wrong choice, I could end up with less. And sometimes this life feels so small, and how could I live with any less?

I am brewing an obstruction right now. I felt it on the train ride home, the pain spiderwebbing out from about an inch behind my stoma. Tonight, I ran a very hot bath to try and move things along in my bowel. I deaccessed my port and took off the ostomy bag and appliance and stepped into the water. I felt myself turning red as I lowered myself down.  I leaned back, resting my hands on my hard, distended abdomen.

I looked at my body, really looked at it for the first time in a long time. I saw the way my skin flushed and mottled. I saw the hives around my stoma where I react to the adhesive from the ostomy appliance. I saw my body struggling to digest. Is this more? Is this the best it will ever be?

I think it’s a blessing that you’re not forced to ever know the exact magnitude of the wrongness of any one decision. I’ll never really know if I made the right choice. I could choose to change nothing and in six months, something completely unforeseen could happen. There’s no way of knowing. I’m grateful for that.

My decision is already made. This sense of loss is normal. This fear of less is normal. And at the end of the day, I am not built for caution. I’m just not. I can’t live with less because I’m scared when there is a chance for more.

I walked around for several minutes after I got out of the tub, just me and no devices. No dangling port access. No occlusive dressing.  No ostomy bag.

It felt alien. And maybe a little bit like hope.