Version May 2024
INTRODUCTION — Cutaneous mastocytosis describes a group of disorders characterized by the presence of excessive numbers of mast cells in the skin. Patients with cutaneous mastocytosis do not fulfill diagnostic criteria for systemic mastocytosis and show no evidence of organ involvement other than the skin.
Forms of cutaneous mastocytosis include three variants recognized by the World Health Organization (WHO) [1]:
●Maculopapular cutaneous mastocytosis (MPCM) or urticaria pigmentosa (UP) with two variants – Monomorphic and polymorphic [2]
●Diffuse cutaneous mastocytosis
●Solitary cutaneous mastocytoma
There are two additional disorders about which there is some controversy surrounding classification:
●Telangiectasia macularis eruptive perstans (TMEP) – This variant is rarely seen without MPCM, and the 2016 classification discontinued use of the term TMEP [2]
●Nodular mastocytosis
There are no therapies that change the natural course of cutaneous mastocytosis, although the prognosis in children is generally good.
The treatment and prognosis of the different forms of cutaneous mastocytosis will be presented here. The clinical manifestations, classification, and diagnosis of cutaneous mastocytosis are reviewed separately. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)
The specific mediators released from mast cells and the symptoms caused by these mediators are reviewed separately. (See "Mast cells: Surface receptors and signal transduction" and "Pathophysiology of anaphylaxis".)
GENERAL MEASURES — The management of cutaneous mastocytosis begins with practical measures, such as the use of lukewarm water for bathing, air conditioning during hot weather, and avoidance of triggers for mast cell degranulation. All patients/caretakers should be periodically trained in how to recognize and treat anaphylaxis and should carry an epinephrine autoinjector at all times.
Preparation for treating possible anaphylaxis — Children with extensive skin involvement or elevated serum baseline tryptase may be at increased risk for anaphylaxis from a variety of triggers [3,4], although the risk of anaphylaxis in children with cutaneous mastocytosis is much smaller than that of adult patients with systemic disease (9 versus 49 percent cumulative incidence according to one series) [5]. One series found that children with tryptase levels >6 ng/mL are more likely to require daily antimediator treatment to manage symptoms and prevent severe episodes, and those with levels >15.5 ng/mL were at risk for hospitalization due to severe symptoms [3].
Epinephrine is the primary treatment for anaphylaxis. Mastocytosis patients or their caretakers should have at least two doses of epinephrine in a self-injectable form available at all times for treatment of possible anaphylaxis, since a single dose may be inadequate to counteract a massive release of mediators. Clinicians should also make patients and caregivers aware of the importance of lying down with the legs elevated during anaphylaxis involving hypotension. Hypotension during anaphylaxis is more common than asthma or laryngeal edema in patients with mastocytosis, and ensuring that patients are placed in this position as soon as possible is an important therapeutic intervention. The treatment of anaphylaxis in adults and children is discussed elsewhere. (See "Anaphylaxis: Emergency treatment".)
Mastocytosis patients should consider wearing a medical identification bracelet and should carry an anaphylaxis emergency action plan or wallet card that identifies the condition and describes the proper treatment of anaphylaxis (Anaphylaxis Emergency Action Plan – English) (Anaphylaxis Emergency Action Plan – Spanish) (Anaphylaxis Emergency Action Plan – Wallet card).
Trigger avoidance — Patients should avoid exposures that trigger or aggravate their symptoms, to the extent possible. These exposures may include heat, humidity, cold, emotional stress, exercise, alcohol, and lack of sleep. In infants and young children, irritability (fussing, whining, anger), overexcitement, fever, teething, and skin rubbing can induce symptoms [3]. Spicy foods, such as those containing capsaicin, may cause flushing, nasal congestion, and gastrointestinal symptoms in some patients. Patients should avoid only those triggers that bother them. Empiric avoidance of these factors by all patients is not necessary.
Problematic medications — There are various medications that may cause mast cell activation in patients with either cutaneous or systemic mastocytosis. As a precaution, these medications should be avoided when possible, unless the patient's tolerance for a specific agent is already known.
Potentially problematic medications include the following:
●Opioid analgesics, such as morphine and codeine [6].
●Vancomycin [7,8].
●Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac.
●Radiocontrast agents.
●Certain muscle relaxants – Succinylcholine is more likely to cause immunoglobulin E (IgE)-mediated anaphylaxis than nondepolarizing agents, such as pancuronium or vecuronium. In addition, atracurium can cause direct mast cell activation, and rocuronium has been implicated as an etiology of anaphylactic reactions [9].
Despite the potential for problems with the medications listed above, the majority of patients do tolerate these drugs. A study reviewed anesthetic management of 22 children with mastocytosis (14 with cutaneous and 8 with systemic disease) [10]. Most of these patients were receiving medications to counteract mast cell mediators, which were continued before and after the procedures, although other medications were administered at the discretion of the anesthesiologist. The study found that the perioperative courses were uncomplicated and without serious adverse events. Another retrospective series found that among 45 children with mastocytosis, most of whom had cutaneous disease, general anesthesia was usually well-tolerated [11].
Medications that are usually tolerated — Most patients tolerate acetaminophen, local anesthetics, and benzodiazepines. Fentanyl appears to be a less potent mast cell degranulator than morphine in equimolar concentrations in vitro, although fentanyl has not been specifically studied in patients with mastocytosis.
If anesthesia is required in a patient with no previous history of exposure to anesthetics, certain agents, such as propofol, etomidate, ketamine, fentanyl, cisatracurium, and pancuronium, are recommended over others [12]. A volatile anesthetic, such as sevoflurane, can be used to maintain anesthesia. However, allergic reactions to any medication can develop without precedent, and the clinician must be prepared to handle any such reaction.
Premedication before anticipated trigger exposure — Patients can be premedicated in advance of an anticipated exposure to a possible or known trigger. The approach for patients with cutaneous mastocytosis is similar to that for those with systemic mastocytosis and is presented elsewhere.
Children with diffuse cutaneous mastocytosis can be especially sensitive to all provoking factors and vaccinations, and exposure can trigger exacerbations and bullous eruptions. Premedication is recommended for procedures involving general anesthesia or radiocontrast injection and before the administration of vaccines. We suggest the combination of prednisone (up to 0.5 to 1 mg/kg), as well as both H1 and H2 antihistamines.
Treatment of coexistent allergic disease — Patients with mastocytosis may have concomitant allergic diseases, including allergic rhinitis, asthma, food allergies, and drug allergies [13-16]. However, the incidence of allergic disease in patients with mastocytosis does not appear to be increased, compared with the general population. In most cases, these conditions should be managed as they would be in patients without mastocytosis. (See "Pharmacotherapy of allergic rhinitis" and "An overview of asthma management".)
The administration of subcutaneous immunotherapy for respiratory allergies warrants careful consideration in patients with mastocytosis, because they are at greater risk for systemic reactions and anaphylaxis as a consequence of the therapy itself.
Hymenoptera venom hypersensitivity — Patients with systemic mastocytosis are at increased risk for anaphylaxis in response to Hymenoptera stings, compared with patients who are sensitive to these venoms but do not have mastocytosis. Patients with elevated tryptase levels are at greater risk for anaphylaxis [3,17]. Less is known about the risk of sting-induced anaphylaxis in children with cutaneous mastocytosis. Patients with IgE-mediated systemic reactions to Hymenoptera stings should be offered venom immunotherapy to reduce the risk of anaphylaxis upon subsequent stings. (See 'Treatment of coexistent allergic disease' above.)
Despite the risk of systemic allergic reactions to immunotherapy, venom immunotherapy has been shown to be beneficial for patients with cutaneous (or systemic) mastocytosis who have evidence of venom-specific IgE (ie, positive skin or IgE tests to Hymenoptera venoms) [16]. Therefore, venom immunotherapy is recommended for patients with cutaneous or systemic mastocytosis, who also have a history of systemic symptoms following a known or suspected sting, and evidence of venom-specific IgE. The evaluation and management of Hymenoptera venom reactions in patients with mastocytosis are discussed separately. The use of omalizumab, anti-IgE, has helped during immunotherapy to provide maintenance to patients with severe initial reactions and reactions with build-up of immunotherapy [18].
The optimal approach in children with cutaneous mastocytosis and Hymenoptera reactions is not known, and management should be guided by recommendations for children with Hymenoptera allergy but without mastocytosis. (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action", section on 'Indications and patient selection'.)
PHARMACOLOGIC THERAPIES — The pharmacologic treatment of cutaneous mastocytosis is comprised of medications to prevent mast cell-mediator release and when mediator release does occur, to reduce the resulting symptoms. There are no large randomized, controlled trials evaluating different therapies in cutaneous mastocytosis, and recommendations are based upon extrapolation from allergic diseases, small series, and expert opinion.
Diffuse cutaneous disease and urticaria pigmentosa — For both children with cutaneous disease and adults with urticaria pigmentosa (UP), oral antihistamines are administered to control itching and flushing [19]. Oral sodium cromolyn is helpful for patients with gastrointestinal symptoms (which are reported by over one-third of patients with cutaneous mastocytosis).
Antihistamines — Both H1 and H2 antihistamines are useful in the treatment of cutaneous mastocytosis. H1 antihistamines are administered to prevent flushing and itching. H2 antihistamines are helpful in controlling abdominal pain, heartburn, cramping, and/or diarrhea and may enhance the antipruritic effects of H1 antihistamines.
●Commonly used H1 antihistamines (adult dosing) include oral cetirizine (10 mg daily), fexofenadine (180 mg daily), loratadine (10 mg daily), levocetirizine (5 mg daily), desloratadine (5 mg daily), or hydroxyzine (25 mg every six hours) [20]. Each of these agents may be used in children at age/weight-appropriate doses. In some patients, a combination of two or more H1 antihistamines may provide better symptom control than the use of a single agent. Some patients may benefit from twice daily dosing of nonsedating antihistamines.
●H2 antihistamines (adult dosing) include oral famotidine (20 mg twice daily) and cimetidine (400 mg twice daily) [20]. Famotidine may be used in children at age/weight-appropriate doses.
●Ketotifen, which has been reported to have both mast cell-stabilizing and H1 antihistamine properties, is used to control mast cell activation and pruritus and can be used as a first-line agent where available, although it can be quite sedating for some patients. This drug is not available in oral form in the United States. The adult dose is 2 to 4 mg orally every 12 hours [21]. Ketotifen may be used in children at age/weight-appropriate doses. A double-blind, placebo-controlled trial showed no advantage of ketotifen over hydroxyzine in pediatric mastocytosis [22].
Cromoglycates — Anecdotal evidence suggests that topical cromoglycate ointments may be symptomatically effective for the diffuse skin disease seen in some children with mastocytosis, as well as in adults with UP, although formal studies have not been performed [3,23]. Cromoglycates have been shown to have mast cell-stabilizing properties in vitro, and topical preparations have been studied in the treatment of atopic dermatitis [24,25].
Cromoglycate ointments at strengths ranging from 0.21 to 4 percent have been used in children with mastocytosis [22]. One of the authors (MC) has cromolyn sodium (powder) compounded into hydrated petrolatum to generate a 4 percent ointment. This is applied twice daily to the affected areas to alleviate pruritus and reduce flares. Similar products are available commercially in Europe. Cromoglycates have an excellent safety record in the treatment of pediatric asthma and other diseases, as they are not believed to be systemically absorbed to a significant degree. However, these agents do not cause permanent regression of the skin lesions or alter the natural history of the disease.
In infants with diffuse skin involvement, resolution of pruritus and bullae formation with topical cromoglycates can be seen within three months, although this may vary depending upon severity. Use of the ointment is then tapered to once daily for another month and then continued at the lowest dose that controls symptoms. Adverse effects have not been reported with this therapy.
Cromolyn can also be administered orally (Gastrocrom, 200 mg up to four times daily in patients 13 years or older or 100 mg up to four times daily in patients ages 2 to 12 years) to treat gastrointestinal symptoms caused by mast cell-mediator release, which are present in 20 to 30 percent of patients with cutaneous disease. This medication is generally mixed into a glass of water and taken one hour before meals and then before bed. We typically begin with one or two doses daily and increase gradually to three to four times daily. Some patients do not tolerate this medication because of bloating, cramping, and diarrhea.
Leukotriene-modifying agents — Antileukotriene drugs (eg, montelukast, zafirlukast, or zileuton) may be added in patients with symptoms, such as flushing, itching, abdominal cramping, and recurrent anaphylaxis that are suboptimally controlled by H1 and H2 antihistamines and cromoglycates. These medications rarely cause mood-related side effects, which should be discussed before initiating the therapy. Monitoring of liver function tests is needed with zafirlukast.
Treatment of refractory symptoms — In selected patients with symptoms refractory to cromoglycates, antihistamines, and leukotriene-modifying agents, aspirin and limited use of topical corticosteroids may be helpful.
●Aspirin (in adults only) (up to 325 mg four times daily) may be administered to control flushing, provided the patient is known to tolerate nonsteroidal anti-inflammatory drugs (NSAIDs). This should be administered with caution, because NSAIDs can trigger mediator release in some patients and may precipitate peptic ulcer disease. Techniques for safely administering aspirin to patients with mastocytosis are reviewed separately. Aspirin should not be used concomitantly with other NSAIDs. (See "Advanced systemic mastocytosis: Management and prognosis".)
●Short-term use of topical corticosteroids may be useful for temporarily decreasing the number of skin mast cells and reducing refractory symptoms of mediator release. However, the benefit is short-lived, and this should not be considered a form of long-term management because of the side effects associated with chronic glucocorticoid use, including adrenal suppression if they are applied to large areas. Glucocorticoid creams or ointments may be applied to the skin of children older than two years. For areas <10 percent of body surface area (BSA) or for solitary mastocytomas, the preparation can be applied under an occlusive dressing. For >10 percent BSA, some experts recommend that the topical corticosteroid be diluted one part to three parts and applied for three to six weeks [26].
●Psoralen-ultraviolet A therapy (PUVA) or narrow band UVB decreases the number of mast cells and controls pruritus that cannot be managed with antihistamines alone [27-30]. However, long-term use is associated with an increased risk of skin cancer, and the skin lesions usually recur after therapy is stopped. Phototherapy may be considered for temporary symptomatic relief in patients with diffuse cutaneous mastocytosis with extensive skin involvement refractory to medical management.
●The oral multikinase inhibitor midostaurin (PKC412) appears to reduce skin lesions in patients with indolent systemic mastocytosis and may be similarly useful in cutaneous mastocytosis, although trials have been focused on advanced forms of systemic disease with associated hematopathology. (See "Advanced systemic mastocytosis: Management and prognosis", section on 'Midostaurin'.)
Therapies that are not recommended — With adult forms of UP, several forms of therapy have been used to decrease the number of mast cells in the skin. These therapies provide only temporary relief, do not affect the development of systemic disease, and are associated with side effects. Thus, they are not recommended, although they are included here because their use is a common source of inquiries:
●Systemic glucocorticoids are not recommended for routine management of skin lesions in patients with cutaneous mastocytosis, although brief courses may be considered to control severe symptoms during acute flares, especially in bullous outbreaks of diffuse cutaneous mastocytosis.
●Mast cell cytoreductive therapies, including imatinib, are not indicated in patients with disease limited to skin.
Cutaneous mastocytomas — Physical irritation of the mastocytoma lesion should be avoided, as it may lead to generalized symptoms of mediator release, such as flushing, urticaria, and wheezing.
Surgical removal of mastocytomas is potentially curative if the lesion is resectable, although this is usually not necessary unless patients suffer from uncontrollable symptoms due to mediator release. Mastocytomas rarely recur.
Pharmacotherapy — Oral antihistamines are helpful for symptoms caused by mediator release, as with other forms of cutaneous mastocytosis. (See 'Antihistamines' above.)
Localized application of topical corticosteroids may be beneficial in patients with cutaneous mastocytomas who experience local or generalized symptoms. We suggest a medium-to-high potency preparation initially, applied under an occlusive dressing for 7 to 10 days. (See "Topical corticosteroids: Use and adverse effects".)
MONITORING — Yearly monitoring is appropriate for children with cutaneous mastocytosis and stable symptoms. A complete blood count (CBC) with differential, chemistry panel including alkaline phosphatase, and serum tryptase level are generally sufficient. If the serum tryptase level is found to be consistently >20 ng/mL or if there is an unexplained persistent abnormality in the CBC with differential, hepatomegaly or splenomegaly, or unexplained lymphadenopathy, an evaluation for systemic mastocytosis should be considered.
In all patients who experience onset of skin lesions in adulthood, an evaluation for systemic work-up with a bone marrow biopsy and aspiration should be considered. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)
PROGNOSIS — The prognosis of cutaneous forms of mastocytosis is related to the age at presentation. The presence of kit mutations in lesional skin samples obtained from children with cutaneous mastocytosis has not been found to provide useful prognostic information and is essentially a research tool, but the presence of the KIT D816V mutation in the skin biopsies has been associated with an increased risk for progression to systemic forms [31]. The monomorphic variant of the maculopapular lesions has a prognostic value in children, since children with this presentation have a tendency to progress to systemic mastocytosis [2].
Infants and young children — The prognosis is excellent for children with cutaneous forms of mastocytosis who have onset of skin lesions within the first two years of life, because spontaneous resolution is common after several years (usually before the onset of puberty) [32].
●Mastocytomas in children usually involute spontaneously after several years.
●The lesions of urticaria pigmentosa (UP) in children resolve during adolescence in over 50 percent of patients, with fading or improvement of the lesions in most of the remaining patients.
Overall, more than 80 percent of children with cutaneous mastocytosis experience spontaneous resolution [33,34]. The remaining children may have persistent cutaneous disease or may progress to systemic forms of the disease.
●In a series of 15 patients with onset of mastocytosis in childhood, complete regression of cutaneous findings and symptoms occurred in 10 (67 percent) [33]. Of the remaining 5 patients, 3 had major and 2 had partial regression. Three of those with persistent disease underwent bone marrow examinations and 1 (7 percent of the group) was found to have systemic mastocytosis.
●In a large retrospective series of 1747 pediatric patients (published between 1950 and 2014), the disease regressed or stabilized 94 percent after variable periods of follow-up (1.5 to 55 years) [34]. Aggressive forms of systemic disease (mast cell leukemia or mast cell sarcoma) developed in 3 percent and ultimately proved fatal. Three of these patients also developed germ cell tumors. These findings underline the need for continued monitoring in patients whose symptoms do not completely resolve.
Risk factors for the development of systemic disease include [2]:
●Late onset of skin lesions (beyond two years of age)
●Monomorphic variant
●Persistence of skin lesions beyond adolescence
●Presence of unexplained hepatomegaly, splenomegaly, or lymphadenopathy
●Abnormal blood counts (to detect anemia, leukocytosis, leukopenia, presence of blast forms, or abnormal numbers of platelets)
Evaluation of patients for possible systemic disease is reviewed in detail elsewhere. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)
Older children and adults — Cutaneous mastocytosis that develops after the age of two years or in adulthood tends to persist. Approximately 90 percent of adult patients with skin lesions have evidence of systemic disease at the time of diagnosis, with the majority belonging to the category of indolent systemic mastocytosis. Rare cases of progression of pediatric-onset cutaneous disease to aggressive forms of mast cell disease such as mast cell sarcoma and mast cell leukemia have been reported [35,36].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Mast cell disorders".)
SUMMARY AND RECOMMENDATIONS
●There are no therapies that alter the natural course of cutaneous mastocytosis or urticaria pigmentosa (UP), and management consists of avoiding triggers of mast cell degranulation and pharmacotherapy for symptomatic relief. (See 'Introduction' above.)
●For patients with itching or flushing due to diffuse cutaneous involvement or UP, we suggest H1 antihistamines as initial therapies (Grade 2C). Antihistamines may be administered on a scheduled or as-needed basis, depending upon symptom frequency. We typically begin treatment with nonsedating antihistamines and reserve sedating agents for refractory symptoms or as-needed use. Cromoglycate ointments may also help control cutaneous disease. (See 'Antihistamines' above and 'Cromoglycates' above.)
●For patients with gastrointestinal symptoms, such as abdominal pain, heartburn, cramping, and/or diarrhea, we suggest H2 antihistamines and/or oral cromolyn as initial therapies (Grade 2C). (See 'Antihistamines' above and 'Cromoglycates' above.)
●For patients with flushing, itching, or abdominal symptoms despite the above measures, we suggest the addition of an antileukotriene agent (Grade 2C). (See 'Leukotriene-modifying agents' above.)
●The management of isolated cutaneous mastocytomas involves avoiding physical contact or rubbing of the lesion(s), as this causes mediator release and systemic symptoms. Systemic symptoms are managed primarily with antihistamines. Surgical removal is rarely necessary, unless the patient experiences uncontrollable systemic symptoms. (See 'Cutaneous mastocytomas' above.)
●The prognosis for young children with cutaneous mastocytosis is excellent, because the majority will experience spontaneous resolution before puberty. However, such children should be followed to assure that symptoms have stabilized or resolved. In contrast, cutaneous disease that first develops after two years of age tends to be persistent, and many patients will develop systemic forms of mastocytosis. (See 'Prognosis' above.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
