Q:

5/10/2013
I saw a patient with a 10-year history of cutaneous mastocytosis. Although I am checking a tryptase level, she was diagnosed at Dartmouth medical school, so I assume they were correct. Her symptoms are mild. She takes no daily prophylactic H1 or H2 blockers, and only gets erythematous when she goes in a hot tub or takes a shower. However she did say that she was told that surgery would be dangerous. That's what she wanted my opinion for, as she needs a hip replacement. My feeling was that if her tryptase level was normal, surgery should be fine, although H1 and H2 blockade may still be helpful. I was wondering what your feeling was about this. Thank you very much for your time.

A:

Thank you for your inquiry.

I think that your analysis of the risk of a systemic reaction occurring during surgery in your patient is in general correct. That is, most of our data (which has been obtained mainly from children with urticaria pigmentosa) indicate that surgery is usually safe in patients who have mastocytosis limited to the skin (see abstract copied below - Klein and Misseldine). However, serious reactions in such individuals have been reported (see Hosking and Warner abstract copied below).

In addition, although I agree with you that it is unlikely your patient has an increase in systemic mast cell burden, you do not know this for sure, and a normal baseline serum tryptase would not completely rule out this possibility. Thus, I would advise approaching surgery in this patient as I would in a patient with documented systemic mastocytosis, utilizing a protocol that has been dicussed in a number of publications (see below - Greenblatt and Chen, Castells, et al., and finally Klein and Misseldine). In addition, the article by Castells, et al., has an excellent discussion of the issue of anaphylaxis occurring in patients with urticaria pigmentosa (Section 10 of the article).

So, in summary, even though reactions in patients with a mast cell burden limited to their skin are rare, and surgery is usually performed without difficulty, there are exceptions to this rule. Because of this, I would discuss the issue with her anesthesiologist and approach surgery with a protocol as described in any one of the articles mentioned above.

Thank you again for your inquiry and we hope this response is helpful to you.

Hosking MP, Warner MA. Sudden intraoperative hypotension in a patient with asymptomatic urticaria pigmentosa. Anesth Analg. 1987 Apr;66(4):344-6.
Abstract
Urticaria pigmentosa is a usually benign and asymptomatic cutaneous variant of mastocytosis, a disorder distinguished by abnormal proliferation of tissue mast cells (1,2). Infrequently, the systemic variant of mastocytosis, characterized by abnormal, secretory mast cell aggregations in visceral organs and bone, may be concomitantly found in patients with urticaria pigmentosa (3). These abnormal aggregations, if present, can abruptly release vasoactive mediators such as histamine and prostaglandin D2 and produce acute, profound hypotension. Precipitating factors of release are unclear in most instances.

Although cardiovascular instability during the anesthetic management of patients with symptomatic systemic mastocytosis has been documented (4), there have been no reports of hemodynamic instability during the anesthetic management of patients with previously asymptomatic urticaria pigmentosa. We report a case of profound intraoperative hypotension in an adult patient with asymptomatic urticaria pigmentosa to emphasize to anesthesiologists the association of urticaria pigmentosa and systemic mastocytosis.

Eric P. Greenblatt, MD, Linda Chen, MD. Urticaria pigmentosa: An anesthetic challenge
Journal of Clinical Anesthesia, Volume 2, Issue 2, March–April 1990, Pages 108–115.
Abstract
Urticaria pigmentosa is the most common form of mastocytosis, a disease in which abnormal proliferations of mast cells occur in various organs of the body. Multiple stimuli, including many drugs commonly used in anesthetic practice, can provoke mast cell degranulation and result in intraoperative hemodynamic instability. An anesthetic plan minimizing histamine release and utilizing vecuronium as the muscle relaxant is discussed, and the literature pertaining to urticaria pigmentosa is reviewed.

Klein NJ, Misseldine S. Anesthetic considerations in pediatric mastocytosis: a review. J Anesth. 2013 Feb 14. [Epub ahead of print]
Source
University of California, Davis, 4150 'V' St., PSSB 1200, Sacramento, CA, 95817, USA,
Abstract
Mastocytosis is an orphan disease rarely encountered by practicing anesthesiologists. Children with mastocytosis often present for procedures or surgery requiring anesthesia. Because many of the medications commonly used in pediatric anesthesia have been reported to initiate mast cell activation, parents are often very anxious about their child's perioperative experience. Laboratory investigations of serum histamine assays associated with different anesthetic drugs have not been shown to predict mast cell degranulation in these patients. However, the pediatric literature suggests that children with disease limited to the skin rarely suffer serious side effects from anesthesia, and there are no reported fatalities. Preoperative prophylaxis is usually based on expert opinion and case reports. Detailed tables summarizing reports of anesthetic medications used for children with mastocytosis undergoing anesthesia, reported side effects, and suggested prophylaxis regimens are included in this review.

Castells M, Metcalfe DD, Escribano L. Diagnosis and treatment of cutaneous mastocytosis in children: practical recommendations. Am J Clin Dermatol. 2011 Aug 1;12(4):259-70. doi: 10.2165/11588890-000000000-00000.
Source
Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham Womens Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
Cutaneous mastocytosis in children is a generally benign disease that can present at birth and is often associated with mast cell mediator-related symptoms including pruritus, flushing, and abdominal pain with diarrhea. The most common form of presentation is urticaria pigmentosa, also referred to as maculopapular mastocytosis. Flares of lesions are induced by triggers such as physical stimuli, changes in temperature, anxiety, medications, and exercise. The skin lesions are typically present on the extremities. Symptoms respond to topical and systemic anti-mediator therapy including antihistamines and cromolyn sodium. Remission at puberty is seen in a majority of cases. Progression to systemic mastocytosis with involvement of extracutaneous organs is not common. The cause of cutaneous mastocytosis is unknown and familial cases are rare. Mutations of c-kit have been observed in the skin of those affected. The diagnosis is established on clinical grounds and the findings on skin biopsy. Bone marrow studies are recommended if there is suspicion of progression of disease to an adult form, if cytoreductive therapy is contemplated, or if skin lesions remain present and/or tryptase levels remain elevated after puberty. The use of chemotherapy, including kinase inhibitors, is strongly discouraged unless severe hematologic disease is present, since malignant evolution is extremely rare.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology