Title: Eosinophilic granuloma

{{Short description|Medical condition}}
==Humans==
[[File:Facial_eosinophilic_granuloma.jpg|thumb|right|200px|Lesion on a nose]]
'''Human eosinophilic granuloma''' is characterized by abnormal proliferation of [[Langerhans cell]]s (LCs). LCs are [[antigen-presenting cell]]s derived from [[dendritic cell]]s. In humans, eosinophilic granulomas are considered to be [[Benign tumor|benign]] tumors that occur mainly in children and adolescents. EG is a quite rare condition, and its incidence is higher in white than in black population, also slightly more affecting males than females. EG develops in 4-5 children (aged under 15) per million/year and in 1 or 2 adults per million/year.&lt;ref name=&quot;:0&quot;&gt;{{Citation|last1=Jha|first1=Suman K.|title=Eosinophilic Granuloma|date=2022|url=https://www.ncbi.nlm.nih.gov/books/NBK559038/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=32644464|access-date=2022-01-31|last2=De Jesus|first2=Orlando}}&lt;/ref&gt;

The etiology of EG is not fully understood yet. However, the onset of abnormal LC proliferation may be triggered by viral stimuli ([[Epstein–Barr virus|EBV]], [[Human herpesvirus 6|Human Herpes virus 6]]), bacterial toxins or defective regulation of [[Interleukin-1 family|IL-1]] and [[Interleukin 10|IL-10]] production.&lt;ref&gt;{{Cite journal|last1=Chadha|first1=Manish|last2=Agarwal|first2=Anil|last3=Agarwal|first3=Nidhi|last4=Singh|first4=Manoj Kumar|date=June 2007|title=Solitary eosinophilic granuloma of the radius. An unusual differential diagnosis|journal=Acta Orthopaedica Belgica|volume=73|issue=3|pages=413–417|issn=0001-6462|pmid=17715738}}&lt;/ref&gt; Another possible explanation may be a defect in [[Ras/MapK pathway|Ras/MAPK]] signaling pathway due to mutation of signaling proteins. Particularly, it was published that about 50% of the EG cases had mutated [[BRAF (gene)|BRAF]] V600 E gene&lt;ref&gt;{{Cite journal|last1=Badalian-Very|first1=Gayane|last2=Vergilio|first2=Jo-Anne|last3=Degar|first3=Barbara A.|last4=MacConaill|first4=Laura E.|last5=Brandner|first5=Barbara|last6=Calicchio|first6=Monica L.|last7=Kuo|first7=Frank C.|last8=Ligon|first8=Azra H.|last9=Stevenson|first9=Kristen E.|last10=Kehoe|first10=Sarah M.|last11=Garraway|first11=Levi A.|date=2010-09-16|title=Recurrent BRAF mutations in Langerhans cell histiocytosis|journal=Blood|volume=116|issue=11|pages=1919–1923|doi=10.1182/blood-2010-04-279083|issn=1528-0020|pmc=3173987|pmid=20519626}}&lt;/ref&gt; and about 21% displayed a mutation in [[MAP2K1|MAP2K]]1.&lt;ref&gt;{{Cite journal|last1=Tran|first1=Gary|last2=Huynh|first2=Thy N.|last3=Paller|first3=Amy S.|date=March 2018|title=Langerhans cell histiocytosis: A neoplastic disorder driven by Ras-ERK pathway mutations|journal=Journal of the American Academy of Dermatology|volume=78|issue=3|pages=579–590.e4|doi=10.1016/j.jaad.2017.09.022|issn=1097-6787|pmid=29107340|s2cid=46767736}}&lt;/ref&gt;

===Signs and symptoms===
Clinically, single or multiple lesions are present mostly on the axial skeleton - on the skull, spine, ribs, pelvis and long bones. Specifically, thoracic spine and frontal bone within the skull are the most affected in children. On the other hand, cervical spine and jaw bone are the major spots of EG lesions in adults. Symptoms of EG include stiffness, local pain, edema of surrounding tissues, posture change, and many others, depending on the affected bone.&lt;ref name=&quot;:0&quot; /&gt;

Lung EG is even less common. Its prevalence has not been published, however, lung EG was already diagnosed in approximately 5% of all lung biotic samples. Such condition may be asymptomatic, but also a non-productive cough, dyspnea, chest pain, fatigue, and spontaneous pneumothorax can occur.&lt;ref name=&quot;:0&quot; /&gt; Higher risk of lung EG is being associated with smoking.&lt;ref&gt;{{Cite journal|last1=Ma|first1=Jennifer|last2=Laird|first2=James H.|last3=Chau|first3=Karen W.|last4=Chelius|first4=Monica R.|last5=Lok|first5=Benjamin H.|last6=Yahalom|first6=Joachim|date=January 2019|title=Langerhans cell histiocytosis in adults is associated with a high prevalence of hematologic and solid malignancies|journal=Cancer Medicine|volume=8|issue=1|pages=58–66|doi=10.1002/cam4.1844|issn=2045-7634|pmc=6346231|pmid=30597769}}&lt;/ref&gt;

===Diagnosis===
Diagnostic options of EG comprise [[X-ray]], [[CT scan|CT]] and [[Magnetic resonance imaging|MR]]. Histopathological examination of the bioptic sample is focused on the presence of mononuclear LCs with prominent nuclear grooves (coffee bean shaped nuclei) with addition of eosinophils. Such examination also utilizes CD1 and [[Langerin|CD207]] (Langerin) staining.&lt;ref&gt;{{Cite journal|last1=Kumar|first1=Neeta|last2=Sayed|first2=Shahin|last3=Vinayak|first3=Sudhir|date=2011-01-20|title=Diagnosis of Langerhans cell histiocytosis on fine needle aspiration cytology: a case report and review of the cytology literature|journal=Pathology Research International|volume=2011|article-number=439518|doi=10.4061/2011/439518|issn=2042-003X|pmc=3034992|pmid=21331166 |doi-access=free }}&lt;/ref&gt; Electron microscopy examination of the sample is based on detection of [[Birbeck granules]], specific &quot;tennis racquet&quot; shaped inclusion within cytoplasm of LCs.&lt;ref name=&quot;:0&quot; /&gt;

=== Treatment ===
Single lesions spontaneously regress often, especially in children, thus are followed up in regular intervals. Patients with spinal lesions are immobilized to minimize the pain. More complicated cases with multiple lesions should be treated with [[corticosteroid]]s, particularly with an intralesional injection of [[methylprednisolone]]. Corticosteroids also represent an option for pulmonary EG treatment.&lt;ref name=&quot;:0&quot; /&gt; Operative treatment includes bone grafting and surgical fixation. In advanced stages of the disease, lung transplantation may be required. High-risk patients with multiple lesions (CNS-risk bones, lungs) may undergo chemotherapy.&lt;ref&gt;{{Cite journal|last1=Kobayashi|first1=Masayuki|last2=Tojo|first2=Arinobu|date=December 2018|title=Langerhans cell histiocytosis in adults: Advances in pathophysiology and treatment|journal=Cancer Science|volume=109|issue=12|pages=3707–3713|doi=10.1111/cas.13817|issn=1349-7006|pmc=6272080|pmid=30281871}}&lt;/ref&gt;

==Cats and dogs==
[[File:Eosinophiles Granulom 2.jpg|thumb|right|250px|Lesion on the upper lip of a [[cat]]]]

===Feline EG===
Feline '''eosinophilic granuloma complex (EGC)''' is a relatively common condition, characterized by a number of patterns affecting oral cavity, skin and mucocutaneous junctions of cats. EGC can be triggered by various stimuli, however, the feline allergic disease is the most relevant one. Among the others, insect bites (fleas), fungi infections and viruses ([[Feline leukemia virus]], [[feline immunodeficiency virus]]) may be responsible.&lt;ref&gt;{{Citation|last1=Muse|first1=Russell|title=CHAPTER 91 - Erosive and Ulcerative Diseases of the Skin|date=2008-01-01|url=https://www.sciencedirect.com/science/article/pii/B9781416039495500959|work=Handbook of Small Animal Practice (Fifth Edition)|pages=885–900|editor-last=Morgan|editor-first=Rhea V.|place=Saint Louis|publisher=W.B. Saunders|language=en|isbn=978-1-4160-3949-5|access-date=2022-01-31|last2=Williamson|first2=Nicola}}&lt;/ref&gt;

Three primary clinical lesions of EGC include indolent (also referred to as eosinophilic or rodent) ulcer, eosinophilic plaque and eosinophilic granuloma.&lt;ref name=&quot;ReferenceA&quot;&gt;{{Cite journal|last1=Hopke|first1=Kaitlin P|last2=Sargent|first2=Sandra J|date=2019-12-16|title=Novel presentation of eosinophilic granuloma complex in a cat|journal=JFMS Open Reports|volume=5|issue=2|article-number=2055116919891548|doi=10.1177/2055116919891548|issn=2055-1169|pmc=6918502|pmid=31897305}}&lt;/ref&gt;

====Signs and symptoms====
The lesions mostly appear on the upper lip as ulcers, but they also develop on the gums and palate. Other locations like foot pads are not exceptional and are typical for developing plaques instead of ulcers.&lt;ref name=&quot;ReferenceA&quot;/&gt; Such plaques may be itchy and swelling. In the case of oral ulceration, bleeding, pain and loss of appetite may be present.&lt;ref name=&quot;:3&quot;&gt;{{Cite web|title=Feline Eosinophilic Granuloma Complex In Cats {{!}} VCA Animal Hospitals|url=https://vcahospitals.com/know-your-pet/feline-eosinophilic-granuloma-complex-in-cats|access-date=2022-01-31|website=vcahospitals.com}}&lt;/ref&gt;

====Treatment====
The treatment of the EGC generally consists of hypoallergenic diet combined with insect bite prevention. Corticosteroids are administered either orally or by long-acting intralesional injections. Alternatively, cyclosporine provides similar effect.&lt;ref name=&quot;:3&quot;&gt;{{Cite web|title=Feline Eosinophilic Granuloma Complex In Cats {{!}} VCA Animal Hospitals|url=https://vcahospitals.com/know-your-pet/feline-eosinophilic-granuloma-complex-in-cats|access-date=2022-01-31|website=vcahospitals.com}}&lt;/ref&gt; Commonly used drugs include: [[trimethoprim/sulfadiazine]], [[cephalexin]], [[amoxicillin]], [[trihydrate]]-[[clavulanate]], [[clindamycin]], [[methylprednisolone]], [[dexamethasone]], [[triamcinolone]], and [[fluocinolone]]. [[Megestrol acetate]] may be used but due to side effects it's only recommended for severe and reoccurring cases.&lt;ref&gt;{{cite book | last1=Rhodes | first1=Karen Helton | last2=Werner | first2=Alexander H. | title=Blackwell's Five-Minute Veterinary Consult Clinical Companion | publisher=Wiley-Blackwell | publication-place=Ames, Iowa | date=2011-01-25 | isbn=978-0-8138-1596-1 | page=123}}&lt;/ref&gt;

===Canine EG===
'''Canine eosinophilic granuloma (CEG)''' is an extremely rare autoinflammatory state affecting primarily oral cavity and surrounding areas of transition between mucosa and hairy skin. However, there have also been described forms affecting lungs or digits.&lt;ref&gt;{{Cite journal|last1=Abbott|first1=Dawn E. E.|last2=Allen|first2=Andrew L.|date=March 2020|title=Canine eosinophilic pulmonary granulomatosis: case report and literature review|journal=Journal of Veterinary Diagnostic Investigation|volume=32|issue=2|pages=329–335|doi=10.1177/1040638720907659|issn=1040-6387|pmc=7081515|pmid=32180541}}&lt;/ref&gt; It may appear independently on the breed or age, although, particular breeds are more prone to the disease, such [[German Shepherd|German shepherds]], [[Labrador Retriever|Labrador retrievers]], [[Siberian Husky|Huskies]] and [[Cavalier King Charles Spaniel|Cavalier King Charles spaniels]]. The disease also tends to appear mainly in dogs aged under 3 years.&lt;ref name=&quot;:1&quot;&gt;{{Cite journal|last1=Mendelsohn|first1=Danielle|last2=Lewis|first2=John R.|last3=Scott|first3=Kristin Iglesias|last4=Brown|first4=Dorothy C.|last5=Reiter|first5=Alexander M.|date=March 2019|title=Clinicopathological Features, Risk Factors and Predispositions, and Response to Treatment of Eosinophilic Oral Disease in 24 Dogs (2000-2016)|journal=Journal of Veterinary Dentistry|volume=36|issue=1|pages=25–31|doi=10.1177/0898756419834785|pmid=31138045|s2cid=169032822|issn=0898-7564|doi-access=free}}&lt;/ref&gt;

Eosinophilic granuloma lesions in dogs primarily consists of eosinophils with addition of various cell subtypes such [[macrophage]]s, [[neutrophil]]s, [[Plasma cell|plasmocytes]], [[lymphocyte]]s, [[mast cell]]s and many others.&lt;ref name=&quot;:1&quot;&gt;{{Cite journal|last1=Mendelsohn|first1=Danielle|last2=Lewis|first2=John R.|last3=Scott|first3=Kristin Iglesias|last4=Brown|first4=Dorothy C.|last5=Reiter|first5=Alexander M.|date=March 2019|title=Clinicopathological Features, Risk Factors and Predispositions, and Response to Treatment of Eosinophilic Oral Disease in 24 Dogs (2000-2016)|journal=Journal of Veterinary Dentistry|volume=36|issue=1|pages=25–31|doi=10.1177/0898756419834785|pmid=31138045|s2cid=169032822|issn=0898-7564|doi-access=free}}&lt;/ref&gt;

====Signs and symptoms====
CEG usually manifests as a plaque on the palate, gums, lips or tongue. These are proliferative white or reddish lesions that may be painful and can be the cause of halitosis and hemorrhage that are often present. Loss of appetite is the most obvious symptom indicating the illness. The lesions may spontaneously appear and wane.&lt;ref name=&quot;:2&quot;&gt;{{Cite journal|last1=Tellado|first1=Matías Nicolás|last2=Michinski|first2=Sebastián Diego|last3=Olaiz|first3=Nahuel|last4=Maglietti|first4=Felipe|last5=Marshall|first5=Guillermo|date=2014-10-16|title=Canine Oral Eosinophilic Granuloma Treated with Electrochemotherapy|journal=Case Reports in Veterinary Medicine|language=en|volume=2014|article-number=e519197|doi=10.1155/2014/519197|issn=2090-7001|doi-access=free|hdl=11336/19287|hdl-access=free}}&lt;/ref&gt; Biopsy is usually required for confirmation of the diagnosis.

====Treatment====
Although the etiology of the disease is not understood completely, it is believed that the most relevant triggers of the autoimmune reaction are various environmental stimuli, especially food allergens and insect bites. Thus, the treatment usually includes transition to hypoallergenic diet and protection from ectoparasites. Medication includes [[Immunosuppressive drug|immunosuppressives]] ([[prednisone]], [[azathioprine]]) either alone, or in combination with [[antibiotic]]s or other drugs ([[cytostatics]] - [[chlorambucil]]). Remission of the lesions may occur in some cases, but in the others low doses of life-long immunosuppression may be necessary.&lt;ref name=&quot;:1&quot; /&gt; Recent publications mention [[electrochemotherapy]] as a novel therapeutical method of CEG providing selective disappearance of the granuloma mass.&lt;ref name=&quot;:2&quot; /&gt;

==References==
&lt;references /&gt;
{{Medical resources
|  DiseasesDB     = 5906 
|  ICD10          = {{ICD10|D|76|0|d|70}} ([[ILDS]] D76.030) 
|  ICD9           = {{ICD9|277.89}} 
|  ICDO           =  
|  OMIM           =  
|  MedlinePlus    =  
|  eMedicineSubj  =  
|  eMedicineTopic =  
|  MeshID         = D004803
}}
{{Histiocytosis}}

[[Category:Cat diseases]]
[[Category:Eosinophilic cutaneous conditions]]