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{{Mast cell tumor}}
{{Mast cell tumor}}
{{CMG}}
{{CMG}};{{AE}} {{PSK}}
==Overview==
==Overview==
The mainstay of therapy for mast cell tumor is avoidance of triggering factors and symptomatic therapy. Chemotherapy is indicated for aggressive form of mast cell tumor.
==Medical Therapy==
==Medical Therapy==
There is currently no cure for mastocytosis. The treatment is palliative and there are a number of medicines to help treat the symptoms of mastocytosis:  
The treatment of mast cell tumor is mainly focused on avoidance of triggering factors (e.g. physical stimuli such as heat or cold, alcohol, stress, sternous exercise, drugs such as aspirin and other NSAIDS) and symptomatic therapy. Commonly used medications for symptomatic relief include:<ref name="KoenigMorel2008">{{cite journal|last1=Koenig|first1=Martial|last2=Morel|first2=Jérôme|last3=Reynaud|first3=Jacqueline|last4=Varvat|first4=Cécile|last5=Cathébras|first5=Pascal|title=An unusual cause of spontaneous bleeding in the intensive care unit – mastocytosis: a case report|journal=Cases Journal|volume=1|issue=1|year=2008|pages=100|issn=1757-1626|doi=10.1186/1757-1626-1-100}}</ref><ref name="pmid14960756">{{cite journal |vauthors=Tolar J, Tope WD, Neglia JP |title=Leukotriene-receptor inhibition for the treatment of systemic mastocytosis |journal=N. Engl. J. Med. |volume=350 |issue=7 |pages=735–6 |date=February 2004 |pmid=14960756 |doi=10.1056/NEJM200402123500723 |url=}}</ref><ref name="pmid10909045">{{cite journal |vauthors=Worobec AS |title=Treatment of systemic mast cell disorders |journal=Hematol. Oncol. Clin. North Am. |volume=14 |issue=3 |pages=659–87, vii |date=June 2000 |pmid=10909045 |doi= |url=}}</ref>
 
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
| valign="top" |
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Medication'''}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Indications'''}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
H1 antihistamine
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Pruritus]]
*[[Flushing]]
*[[Anaphylaxis]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
H2 antihistamine
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Pruritus]]
*[[Anaphylaxis]]
*[[Diarrhea]]
*[[Nausea]]
*[[Vomiting]]
*Abdominal discomfort
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
Antileukotriene drugs
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Flushing
* Pruritus
* Abdominal discomfort
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
Mast cell stabilizers
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Abdominal cramping]]
*[[Malabsorption]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
[[Proton pump inhibitors]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Peptic ulcers
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
[[Epinephrine]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Anaphylaxis
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
Steroids
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Anaphylaxis
*[[Malabsorption]]
|}


====Antihistamines====
====Antihistamines====
*[[Antihistamine]]s block receptors targeted by histamine released from mast cells. Both H1 and H2 blockers may be helpful.
*[[Antihistamines]] block receptors targeted by histamine released from mast cells. Both H1 and H2 blockers may be helpful.
*[[Leukotriene antagonists]] block receptors targeted by leukotrienes released from mast cells.
*[[Leukotriene antagonists]] block receptors targeted by leukotrienes released from mast cells.
*Antihistamines frequently treat itching and other skin complaints.
*Certain antihistamines work specifically against ulcers


====Mast cell stabilizers====
====Mast cell stabilizers====
*[[Mast cell stabilizer]]s help prevent mast cells from releasing their chemical contents. Cromolyn Sodium Oral Solution (Gastrocrom® / [[Cromoglicate]]) is the only medicine specifically approved by the U.S. FDA for the treatment of mastocytosis. [[Ketotifen]] is available in Canada and Europe, but is only available in the U.S. as ophthamic drops (Zaditor®).
*[[Mast cell stabilizer]]s help prevent mast cells from releasing their chemical contents.  
*Cromolyn sodium oral solution (Gastrocrom® / [[Cromoglicate]]) is the only medicine specifically approved by the U.S. FDA for the treatment of mastocytosis.  
*[[Ketotifen]] is available in Canada and Europe, but is only available in the U.S. as ophthalmic drops (Zaditor®).
*Cromolyn sodium may help reduce cramping in the abdomen.


====Proton pump inhibitors====
====Proton pump inhibitors====
*[[Proton pump inhibitor]]s help reduce production of gastric acid, which is often increased in patients with mastocytosis. Excess gastric acid can harm the stomach, esophagus, and small intestine.  
*[[Proton pump inhibitor]]s help reduce production of gastric acid, which is often increased in patients with mastocytosis.
*Excess gastric acid can harm the stomach, esophagus, and small intestine.


====Epinephrine====
====Epinephrine====
*[[Epinephrine]] constricts blood vessels and opens airways to maintain adequate circulation and ventilation when excessive mast cell degranulation has caused [[anaphylaxis]].
*[[Epinephrine]] constricts blood vessels and opens airways to maintain adequate circulation and ventilation when excessive mast cell degranulation has caused [[anaphylaxis]].
*Epinephrine treats symptom flares which occur with shock, referred to as "anaphylaxis".
*In case of repeated life-threatening anaphylactoid episodes, the self-administration of epinephrine on demand has been recommended as an appropriate approach.<ref name="MolderingsBrettner2011">{{cite journal|last1=Molderings|first1=Gerhard J|last2=Brettner|first2=Stefan|last3=Homann|first3=Jürgen|last4=Afrin|first4=Lawrence B|title=Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options|journal=Journal of Hematology & Oncology|volume=4|issue=1|year=2011|pages=10|issn=1756-8722|doi=10.1186/1756-8722-4-10}}</ref>


====Albuterol====
====Albuterol====
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====Steroid====
====Steroid====
*[[Corticosteroids]] can be used topically, inhaled, or systemically to reduce inflammation associated with mastocytosis.
*[[Corticosteroids]] can be used topically, inhaled, or systemically to reduce inflammation associated with mastocytosis.
*Steroids treat malabsorption or impaired ability to take in nutrients.


====Antidepressants====
====Antidepressants====
*[[Antidepressant]]s are an important and often overlooked tool in the treatment of mastocytosis. The stress and physical discomfort of any chronic disease may increase the likelihood of a patient developing [[clinical depression|depression]]. Depression and other neurological symptoms have been noted in mastocytosis.<ref>Rogers MP, Bloomingdale K, Murawski BJ, Soter NA, Reich P, Austen KF. ''Mixed organic brain syndrome as a manifestation of systemic mastocytosis.'' Psychosom Med 1986;48:437-47. PMID 3749421</ref> Some antidepressants such as [[doxepin]] are themselves potent antihistamines and can help relieve physical as well as cognitive symptoms.  
*[[Antidepressant]]s are an important and often overlooked tool in the treatment of mastocytosis.
*The stress and physical discomfort of any chronic disease may increase the likelihood of a patient developing [[clinical depression|depression]].
*Depression and other neurological symptoms have been noted in mastocytosis.<ref>Rogers MP, Bloomingdale K, Murawski BJ, Soter NA, Reich P, Austen KF. ''Mixed organic brain syndrome as a manifestation of systemic mastocytosis.'' Psychosom Med 1986;48:437-47. PMID 3749421</ref> Some antidepressants such as [[doxepin]] are themselves potent antihistamines and can help relieve physical as well as cognitive symptoms.


====Calcium channel blocker====
====Calcium channel blocker====
*[[Dihydropyridines]] are [[calcium channel blocker]]s that are sometimes used to treat [[hypertension|high blood pressure]]. At least one clinical study suggested that [[Nifedipine]], one of the dihydropyridines, may reduce mast cell degranulation in patients that exhibit [[urticaria pigmentosa]]. A 1984 study by Fairly et al. included a patient with symptomatic urticaria pigmentosa who responded to nifedipine at dose of 10 mg po tid.<ref>Fairley JA, et al: Urticaria pigmentosa responsive to nifedipine. J Am Acad Dermatol 11:740-743, 1984.</ref> However, Nifetipine has never been approved by the FDA for treatment of mastocytosis.
*[[Dihydropyridines]] are [[calcium channel blocker]]s that are sometimes used to treat [[hypertension|high blood pressure]].
 
*At least one clinical study suggested that [[nifedipine]], one of the dihydropyridines, may reduce mast cell degranulation in patients that exhibit [[urticaria pigmentosa]].<ref>Fairley JA, et al: Urticaria pigmentosa responsive to nifedipine. J Am Acad Dermatol 11:740-743, 1984.</ref>
*However, Nifedipine has never been approved by the FDA for treatment of mastocytosis.


The treatment of systemic mastocytosis is mainly focused on avoidance of triggering factors (e.g. physical stimuli such as heat or cold, alcohol, drugs such as aspirin and other NSAIDS) and symptomatic therapy (H1 and H2 antihistamines, proton pump inhibitors, antileukotrienes, anticholinergics, glucocorticoïds, and epinephrine in case of systemic hypotension). In aggressive forms of systemic mastocytosis, treatments such as interferon alpha, cladribin, and imatinib mesylate should to be considered. Imatinib seems to be more effective in patients without the D816V C-kit mutation.<ref name="KoenigMorel2008">{{cite journal|last1=Koenig|first1=Martial|last2=Morel|first2=Jérôme|last3=Reynaud|first3=Jacqueline|last4=Varvat|first4=Cécile|last5=Cathébras|first5=Pascal|title=An unusual cause of spontaneous bleeding in the intensive care unit – mastocytosis: a case report|journal=Cases Journal|volume=1|issue=1|year=2008|pages=100|issn=1757-1626|doi=10.1186/1757-1626-1-100}}</ref>
===Chemotherapy===
*In rare cases in which mastocytosis is cancerous or associated with a blood disorder, the patient may have to use [[steroid]]s and/or [[chemotherapy]].
*The novel agent [[imatinib]] (Glivec® or Gleevec®) has been found to be effective in certain types of mastocytosis.<ref>Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial.  Cancer. 2006 Jul 15;107(2):345-51. PMID 16779792</ref>
*Recent literature shows that C-Kit (D816V) lends some resistance to imatinib and [[sorafenib]] but these cells are still sensitive to [[nilotinib]], [[dasatinib]] and [[rapamycin]]. [[Cladribine]] and [[interferon]] have also  been found to be effective.
===Immunotherapy===
*A difficult situation is the occurrence of life-threatening anaphylaxis in patients with mast cell tumor.<ref name="MolderingsBrettner2011">{{cite journal|last1=Molderings|first1=Gerhard J|last2=Brettner|first2=Stefan|last3=Homann|first3=Jürgen|last4=Afrin|first4=Lawrence B|title=Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options|journal=Journal of Hematology & Oncology|volume=4|issue=1|year=2011|pages=10|issn=1756-8722|doi=10.1186/1756-8722-4-10}}</ref>
*If anaphylaxis is provoked by a known allergen, especially hymenoptera venom, immunotherapy should be considered with recognition of potential risks.


Healthcare providers use several medicines to treat mastocytosis symptoms, including antihistamines (to prevent the effect of mast cell histamine—a chemical) and anticholinergics (to relieve intestinal cramping). A number of medicines treat specific symptoms of mastocytosis.
==Cutaneous Mastocytosis==
*Usually, Isolated cutaneous mastocytosis needs no treatment or action to be taken.<ref name="FerranteScavone2015">{{cite journal|last1=Ferrante|first1=Giuliana|last2=Scavone|first2=Valeria|last3=Muscia|first3=Maria|last4=Adrignola|first4=Emilia|last5=Corsello|first5=Giovanni|last6=Passalacqua|first6=Giovanni|last7=La Grutta|first7=Stefania|title=The care pathway for children with urticaria, angioedema, mastocytosis|journal=World Allergy Organization Journal|volume=8|issue=1|year=2015|pages=5|issn=1939-4551|doi=10.1186/s40413-014-0052-x}}</ref>
*Cutaneous mastocytosis with cosmetic complaints should be treated by a topical therapy only in children older than 2 years.
*When cutaneous mastocytosis is confined to about 10% of body surface, occlusive dressing is used.
*When the extension is larger, (more than 10%) the occlusive dressing is optional, and usually the corticosteroid cream is diluted.
*In cutaneous mastocytosis with complaints of itch, redness, and swelling, avoiding foods with a possible triggering role has to be suggested.


*Antihistamines frequently treat itching and other skin complaints.  
==Diffuse cutaneous mastocytosis==
*Certain antihistamines work specifically against ulcers; proton pump inhibitors also relieve ulcer-like symptoms.  
*Diffuse cutaneous mastocytosis is self-limiting, and the need for a treatment is questionable.<ref name="FerranteScavone2015">{{cite journal|last1=Ferrante|first1=Giuliana|last2=Scavone|first2=Valeria|last3=Muscia|first3=Maria|last4=Adrignola|first4=Emilia|last5=Corsello|first5=Giovanni|last6=Passalacqua|first6=Giovanni|last7=La Grutta|first7=Stefania|title=The care pathway for children with urticaria, angioedema, mastocytosis|journal=World Allergy Organization Journal|volume=8|issue=1|year=2015|pages=5|issn=1939-4551|doi=10.1186/s40413-014-0052-x}}</ref>
*Epinephrine treats symptom flares which occur with shock, referred to as "anaphylaxis."
*If diffuse cutaneous mastocytosis causes significant distress, leads to frequent hospitalizations, or is life-threatening, treatment with [[imatinib]] is a good option.
*Two types of antihistamines treat severe flushing and low blood pressure before symptoms appear.  
*Imatinib mesylate, a type II kinase inhibitor, inhibits cell proliferation and induces [[apoptosis]] by binding the [[adenosine triphosphate]] pocket and the adjacent site of the kinase.
*Steroids treat malabsorption, or impaired ability to take in nutrients.  
*The nonselectivity of [[imatinib]] also explains side effects such as [[cardiomyopathy]] and reduced growth velocity, the latter being a relevant side effect in children.
*Cromolyn sodium may help reduce cramping in the abdomen.
*A dose of 200 mg/m2/day have been used in children, and reducing the dosage as soon as sustained healing of the skin lesions is noted is sufficient to obtain remission.
In cases in which mastocytosis is malignant, cancerous, or associated with a blood disorder, steroids and/or chemotherapy may be necessary.


==References==
==References==
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Latest revision as of 01:55, 25 March 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Suveenkrishna Pothuru, M.B,B.S. [2]

Overview

The mainstay of therapy for mast cell tumor is avoidance of triggering factors and symptomatic therapy. Chemotherapy is indicated for aggressive form of mast cell tumor.

Medical Therapy

The treatment of mast cell tumor is mainly focused on avoidance of triggering factors (e.g. physical stimuli such as heat or cold, alcohol, stress, sternous exercise, drugs such as aspirin and other NSAIDS) and symptomatic therapy. Commonly used medications for symptomatic relief include:[1][2][3]

Medication Indications

H1 antihistamine

H2 antihistamine

Antileukotriene drugs

  • Flushing
  • Pruritus
  • Abdominal discomfort

Mast cell stabilizers

Proton pump inhibitors

  • Peptic ulcers

Epinephrine

  • Anaphylaxis

Steroids

Antihistamines

  • Antihistamines block receptors targeted by histamine released from mast cells. Both H1 and H2 blockers may be helpful.
  • Leukotriene antagonists block receptors targeted by leukotrienes released from mast cells.
  • Antihistamines frequently treat itching and other skin complaints.
  • Certain antihistamines work specifically against ulcers

Mast cell stabilizers

  • Mast cell stabilizers help prevent mast cells from releasing their chemical contents.
  • Cromolyn sodium oral solution (Gastrocrom® / Cromoglicate) is the only medicine specifically approved by the U.S. FDA for the treatment of mastocytosis.
  • Ketotifen is available in Canada and Europe, but is only available in the U.S. as ophthalmic drops (Zaditor®).
  • Cromolyn sodium may help reduce cramping in the abdomen.

Proton pump inhibitors

  • Proton pump inhibitors help reduce production of gastric acid, which is often increased in patients with mastocytosis.
  • Excess gastric acid can harm the stomach, esophagus, and small intestine.

Epinephrine

  • Epinephrine constricts blood vessels and opens airways to maintain adequate circulation and ventilation when excessive mast cell degranulation has caused anaphylaxis.
  • Epinephrine treats symptom flares which occur with shock, referred to as "anaphylaxis".
  • In case of repeated life-threatening anaphylactoid episodes, the self-administration of epinephrine on demand has been recommended as an appropriate approach.[4]

Albuterol

  • Albuterol and other beta-2 agonists open airways that can constrict in the presence of histamine.

Steroid

  • Corticosteroids can be used topically, inhaled, or systemically to reduce inflammation associated with mastocytosis.
  • Steroids treat malabsorption or impaired ability to take in nutrients.

Antidepressants

  • Antidepressants are an important and often overlooked tool in the treatment of mastocytosis.
  • The stress and physical discomfort of any chronic disease may increase the likelihood of a patient developing depression.
  • Depression and other neurological symptoms have been noted in mastocytosis.[5] Some antidepressants such as doxepin are themselves potent antihistamines and can help relieve physical as well as cognitive symptoms.

Calcium channel blocker

Chemotherapy

  • In rare cases in which mastocytosis is cancerous or associated with a blood disorder, the patient may have to use steroids and/or chemotherapy.
  • The novel agent imatinib (Glivec® or Gleevec®) has been found to be effective in certain types of mastocytosis.[7]
  • Recent literature shows that C-Kit (D816V) lends some resistance to imatinib and sorafenib but these cells are still sensitive to nilotinib, dasatinib and rapamycin. Cladribine and interferon have also been found to be effective.

Immunotherapy

  • A difficult situation is the occurrence of life-threatening anaphylaxis in patients with mast cell tumor.[4]
  • If anaphylaxis is provoked by a known allergen, especially hymenoptera venom, immunotherapy should be considered with recognition of potential risks.

Cutaneous Mastocytosis

  • Usually, Isolated cutaneous mastocytosis needs no treatment or action to be taken.[8]
  • Cutaneous mastocytosis with cosmetic complaints should be treated by a topical therapy only in children older than 2 years.
  • When cutaneous mastocytosis is confined to about 10% of body surface, occlusive dressing is used.
  • When the extension is larger, (more than 10%) the occlusive dressing is optional, and usually the corticosteroid cream is diluted.
  • In cutaneous mastocytosis with complaints of itch, redness, and swelling, avoiding foods with a possible triggering role has to be suggested.

Diffuse cutaneous mastocytosis

  • Diffuse cutaneous mastocytosis is self-limiting, and the need for a treatment is questionable.[8]
  • If diffuse cutaneous mastocytosis causes significant distress, leads to frequent hospitalizations, or is life-threatening, treatment with imatinib is a good option.
  • Imatinib mesylate, a type II kinase inhibitor, inhibits cell proliferation and induces apoptosis by binding the adenosine triphosphate pocket and the adjacent site of the kinase.
  • The nonselectivity of imatinib also explains side effects such as cardiomyopathy and reduced growth velocity, the latter being a relevant side effect in children.
  • A dose of 200 mg/m2/day have been used in children, and reducing the dosage as soon as sustained healing of the skin lesions is noted is sufficient to obtain remission.

References

  1. ↑ Koenig, Martial; Morel, Jérôme; Reynaud, Jacqueline; Varvat, Cécile; Cathébras, Pascal (2008). "An unusual cause of spontaneous bleeding in the intensive care unit – mastocytosis: a case report". Cases Journal. 1 (1): 100. doi:10.1186/1757-1626-1-100. ISSN 1757-1626.
  2. ↑ Tolar J, Tope WD, Neglia JP (February 2004). "Leukotriene-receptor inhibition for the treatment of systemic mastocytosis". N. Engl. J. Med. 350 (7): 735–6. doi:10.1056/NEJM200402123500723. PMID 14960756.
  3. ↑ Worobec AS (June 2000). "Treatment of systemic mast cell disorders". Hematol. Oncol. Clin. North Am. 14 (3): 659–87, vii. PMID 10909045.
  4. ↑ 4.0 4.1 Molderings, Gerhard J; Brettner, Stefan; Homann, Jürgen; Afrin, Lawrence B (2011). "Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options". Journal of Hematology & Oncology. 4 (1): 10. doi:10.1186/1756-8722-4-10. ISSN 1756-8722.
  5. ↑ Rogers MP, Bloomingdale K, Murawski BJ, Soter NA, Reich P, Austen KF. Mixed organic brain syndrome as a manifestation of systemic mastocytosis. Psychosom Med 1986;48:437-47. PMID 3749421
  6. ↑ Fairley JA, et al: Urticaria pigmentosa responsive to nifedipine. J Am Acad Dermatol 11:740-743, 1984.
  7. ↑ Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006 Jul 15;107(2):345-51. PMID 16779792
  8. ↑ 8.0 8.1 Ferrante, Giuliana; Scavone, Valeria; Muscia, Maria; Adrignola, Emilia; Corsello, Giovanni; Passalacqua, Giovanni; La Grutta, Stefania (2015). "The care pathway for children with urticaria, angioedema, mastocytosis". World Allergy Organization Journal. 8 (1): 5. doi:10.1186/s40413-014-0052-x. ISSN 1939-4551.

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