Mastocytosis

Accumulation and degranulation of mast cells (mastocytosis) in the skin or other organs. A group of disorders characterized by accumulation of mast cells in the skin with or without other organ system involvement. Systemic mastocytosis occurs in approximately 10% of all cases, with proliferation of mast cells in other tissues such as bone, liver, and spleen.

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Mast Cell Disease; Systemic Mast Cell Disease (SMCD).

A classification of mastocytosis has been proposed based on clinical presentation and prognosis (see the WHO Classification of Mastocytosis in Table M-1).

The cutaneous manifestation, urticaria pigmentosa, is the most common form and was first described in 1869.

Rare; approximately 1-4:10,000 live births.

Usually not considered an inherited disease, although there is some evidence of an autosomal dominant pattern in the diffuse cutaneous form. Males and females are affected equally.

There is an excess of mast cells in body tissues, and the clinical expression of the disorder depends upon the pattern of localization of the mast cells to specific organs. Dysregulation of production and function of mast cells is caused by distinct mutations in c-Kit, a type III transmembrane tyrosine kinase. Mediator release by mast cells may occur spontaneously or be triggered by a variety of stimuli. These biochemical substances include histamine and heparin, thought to be the most important, and other enzymes such as chymases, tryptases, and hydrolases. Prostaglandin D2, cytokines (tumor necrosis factor [TNF]-α and TNF-β, interleukin [IL]-3, IL-5, and IL-16), serotonin, leukotrienes, and platelet-activating factor are also released. Among the precipitating factors are trauma, surgery, extremes of temperature, toxins, alcohol, and a variety of drugs (including acetylsalicylic acid, morphine, codeine, thiopentone, lignocaine, gallamine, and d-tubocurarine).

History of recurrent flushes, urticarial wheals, pruritus, dizziness, and headaches. Darier sign is pathognomonic and is defined as development of an urticarial wheal on a lesion after it is stroked. Skin or gastric mucosa biopsies show an increased number of mast cells (>5 per high-power field). Increased blood and urinary levels of histamine. Bone marrow biopsy is not recommended unless there is evidence of systemic disease.

Approximately 65% of patients with mastocytosis present with the disease in childhood (more than half before age 2 years). The remaining 35% develop the disease after puberty and are classified as adult-onset cases. Mastocytosis limited to the skin is primarily a benign disease of children. Systemic internal mastocytosis is more common in adults with infiltration of mast cells in the gastrointestinal tract, skeletal system, lung, kidney, myocardium, and other tissues.

Urticaria pigmentosa is the most frequent form: lesions are red-brown macules, papules, or plaques showing Darier sign. Darier's sign is defined by skin lesions caused by mast cell urtication on rubbing. Described by Ferdinand-Jean Darier, a French dermatologist. Symptoms are pruritus, flushing associated with bathing in cold or hot water, or exercise. Bullae and blistering may appear. It has a favorable outcome.

Mastocytomas are brownish solitary or multiple nodules that can cause flushing and hypotension when traumatized. The course of an isolated mastocytoma is usually spontaneous regression in several years.

Diffuse cutaneous mastocytosis is seen almost only in infants: skin has a thickened appearance and/or a reddish-brown discoloration. Increased risk of flushing, hypotension, and shock; diarrhea and other gastrointestinal manifestations are common.

Bronchospasm may occur. Anemia, leukocytosis, and thrombocytopenia are common problems. Hematologic abnormalities are rare in children with mastocytosis; however, cases of acute lymphocytic leukemia have been observed in children with rapidly progressive and late-onset mastocytosis. Children and adults who have serious systemic involvement have a guarded prognosis, as do neonates with diffuse cutaneous involvement.

Because the main preoperative aim is to reduce the risk of mast cell degranulation, H1 and H2 antagonists can be given. Some patients are on steroid therapy; check for perioperative coverage. High-dose acetylsalicylic acid inhibits prostaglandin synthetase and is effective in controlling episodes of severe vasodilatation normally associated with prostaglandin D2 release. In approximately 5% of patients, however, severe hypotension may be precipitated by acetylsalicylic acid itself. In addition, aspirin has a detrimental effect on bleeding time and must be carefully assessed. Preoperative intradermal skin testing with drugs likely to be used during anesthesia has been recommended but is not useful if known histamine-releasing drugs are avoided. Blood investigations: hemoglobin, platelet count, coagulation studies, and serum electrolytes. Stress can precipitate a reaction, so an appropriate sedative/ hypnotic premedicant should be prescribed.

Both regional anesthesia and general anesthesia have been reported. Care should be taken when handling and positioning the patient to prevent skin irritation and trauma. Core temperature should be measured and actions to maintain normothermia should be continued into the postoperative period. Large-bore intravenous cannula to allow rapid volume replacement.

Avoid use of medications known to trigger histamine release (e.g., morphine, codeine, ketorolac tromethamine, d-tubocurarine, atracurium, thiopentone). Use of propofol as an intravenous anesthetic induction agent has been found to be safe. Inhalational anesthetics tend to inhibit mast cell degranulation, so general anesthesia may be preferred. Adrenaline, antihistamines, bronchodilators, and intravenous fluids should be available for immediate use to treat severe hypotension and bronchospasm or cardiovascular shock.

Carcinoid Syndrome (Thorson-Biörck Syndrome; Flush Syndrome; Cassidy-Scholte Syndrome): Characterized by hot, red flushing of the face, severe and debilitating diarrhea, and asthma attacks. Malignant carcinoid syndrome occurs in fewer than 10% of patients with a carcinoid tumor. Typically, 90% of cases originate from the distal ileum or appendix (the embryologic midgut) and represent 90% of appendiceal tumors.

Zollinger Ellison Syndrome: Caused by a non-beta islet cell, gastrin-secreting tumor of the pancreas; occurs sporadically or as part of an autosomal dominant familial syndrome called multiple endocrine neoplasia type I (MEN I: hyperparathyroidism, pancreatic endocrine tumors, and pituitary tumors). The primary tumor usually is located in the duodenum, pancreas, and abdominal lymph nodes, but ectopic locations have also been described (e.g., heart, ovary, gallbladder, liver, kidney). Abdominal pain is the most common symptom, present in 75% of patients. Diarrhea, abdominal pain, nausea, vomiting, gastrointestinal bleeding, and weight loss.