URTICARIA AND ANGIOEDEMA IN MYASTHENIA GRAVIS PATIENT Hamidah Luthfidyaningrum / Evy Ervianti Case Presentation 6th

2 Background

BACKGROUND URTIKARIA ANGIOEDEMA A skin disorder characterized by local transient skin or mucosal edema (wheal) and an area of redness (erythema) that typically accompany itchy sensations and diminish within a day Local and transient skin or mucosal edema that develops in deep tissues mostly without itching but may accompany pain or burning sensation

BACKGROUND  MYSTHENIA GRAVIS MG is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatigability. The muscle weakness is caused by a disruption in normal neuromuscular transmission by binding of autoantibodies to proteins involved in signaling the Neuromuscular Junction Keesey, J. C. (2004). Clinical evaluation and management of myasthenia gravis. Muscle & Nerve, 29(4), 484–505

5 Patient Identity

Name : Ny. M Sex: Female Age: 42 years old Body Weight: 55 kg Address: Surabaya Registration No.: Registered : Came to policlinc on November 10 th 2020

7 Chief Complaint

8 Chief Complaint Sweeling and hives on the skin

Discussion The patient complained about hive and sweeling on the leg and face The initial complaint begins with the appearance of hives and then spreads and becomes sweels in the area around the eyes and lips She has been suffering with hives for the past 4 months. She is unable to tell what triggers her hives The patient said that complaints like this often occur, do not have a certain time and Usually it will disappear on its own within 2-3 days

Discussion Nausea, vomiting, diarrhea are denied The history of hypertension was denied, history of DM, drug and food allergies were denied, asthma was denied

History The history of teeth caries since 1 year should have been extracted but it has not been done Patients have a history of myasthenia gravis since 2006 and regularly control to internal departmen and routinely get the drug : mestinon Family history  The patient's younger sibling had a penicillin allergy, atopy was denied Psychosocial history The patient is married but has no children

12 Physical Examination

Physical Examintion  Height : 160 cm, Weight : 55 kg  Blood Pressure: 120/80 mmHg, Heart Rate : 84x/m,  Respiratory Rate : 18x/m, Temp :37.1  C  Head / neck : Enlargement of lymph nodes (-)  Thorax : simetris, scar on the midsternum in the thorax, vesicular +/+  Abdomen : Hepar / Lien : not palpable  Upper and lower extremities : warm, oedema (-/-)

Hb: 10.7 RBC: 5.39 HCT: 46.9 MCV: 87 MCHC: 33.5 WBC: 8.24 Eo: 0.5% Baso: 0.4% Neu: 63.0% (40-60%) Lymph: 27.2% Mono: 8.9% Plt: 328 GDA: 99 Albumin: 3.63 Na: 143 Kalium: 3.7 Cl: 105 CRP: 0.1 OT/ PT: 34/27 BUN: 7 SK: 0.6 LABORATORY RESULT

Dermatological Examination Periorbital Regio erythema +, angioedema +, eye secrete – Oris Regio Angioedema + involving the upper lip Extremitas Inferior Regio Multiple urticaria with variable size and shape, diameter +/- 1,5 – 3 cm and multiple red macules unsharply marginated with variable size

10 November 2020

17 Assessment

Assessment : Urticaria et Angioedema in Mysthenia Gravis Patient

1.Cetirizine 10 mg 2x1 2.Dexametason 0,5mg 3x1 Therapy Patient complaint Stop all suspected drugs Monitoring Explain about the disease Not to manipulate lesion or apply topical medicine other than prescription Education

Dermatology If there is no contraindication in Internal Department : 1.Stop all suspected drugs 2.Cetirizine 10 mg 2x1 3.Dexametason 0,5mg 3x1 Internal 1.Mestinon 4x60mg 2.Mecobalamin 2x250mg

13 November 2020

22 Disscussion

Definition Urticaria is a skin disorder characterized by local transient skin or mucosal edema (wheal) and an area of redness (erythema) that typically accompany itchy sensations and diminish within a day Angioedema is a local and transient skin or mucosal edema that develops in deep tissues mostly without itching but may accompany pain or burning sensations Fitzpatrick 9 th edition

PREVALENCE The lifetime prevalence for all types of urticaria is 8.8%, but chronic urticaria only develops in 30–45% of these individuals Chronic Spontaneus Urticaria is accompanied by angioedema in approximately 40% of cases Up to 40% of patients who have chronic urticaria longer than six months will still have urticaria 10 years later All age groups can be affected, however the peak incidence is seen between 20 and 40 years of age. Fitzpatrick 9 th edition, M. Siannoto, 2017

Clinical Features 1. Cutaneous Findings Wheals  circumscribed, raised, usually pruritic, and evanescent areas of edema that involve the superficial portion of the dermis, wheal may appear mostly reddish but could also be whitish, especially when edema is significant Angioedema  edema that extends into the deep dermis/subcutaneous and submucosal layers, >>face, especially the eyelids and lips/a portion of the extremities 2. Noncutaneous Findings Discomfort of the stomach and intestine  infection of the GIT may induce urticaria Headache, dizziness, syncope Pharyngeal edema Anaphylaxis Fitzpatrick 9 th edition

Clinical Appearance A wheal consists of three typical features: 1.A central swelling, surrounded by a reflect erythema 2.Associated with itching or sometimes a burning sensation 3. A fleeting duration of usually 1 – 24 h. Angioedema is characterized by: 1.A sudden, pronounced erythematous or skin colored swelling of the lower dermis and subcutis with frequent involvement below mucous membranes 2.Sometimes pain rather than icthing, and it resolution is slower than wheals, up to 72 h. Angio-oedema of the lip (a) during and (b) 3 days after an attack. (Courtesy of St John’s Institute of Dermatology, London, UK.) Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. The 2013 revision and update. Allergy 2014;69:868–87

Duration of Chronic Urticaria  In most cases, the duration of CSU is estimated to be 1–5 years 1  However, for some patients the disease can last longer, sometimes more than 25 years 1 Year 25 Years since diagnosis Year 1Year 2Year 3Year 4Year 5 Another 20% will resolve (with or without treatment) within 5 years of onset 2 50% will resolve (with or without treatment) within 6 months of onset 2 Another 20% will resolve (with or without treatment) within 3 years of onset 2 Another <2% will resolve (with or without treatment) within 25 years 2 1. Maurer M, et al. Allergy 2011;66:317–30; 2. Beltrani VS. Clin Rev Allergy Immunol 2002;23:147–69

Urticaria and Angioedema. Zuberbier T, Grattan C, Maurer M, editors. Berlin: Springer-Verlag, 2015 MC, mast cell Urticaria Pathogenesis Symptoms are brought about by the degranulation of skin mast cells MC Release of Mediators including Histamine Release of Mediators including Histamine PRURITUS ERYTHEMA WHEAL INFILTRATE Activation Vasodilation Extravasation Recruitment CAUSECAUSE CAUSECAUSE Mast cells are the key effector cells in the induction of urticaria symptoms IgE Fc  RI

Theory In My Case Name : Mr. E Sex: Female Age: 40 years old Fitzpatrick 9 th edition

Theory In My Case Periorbital Regio Angioedema + erythema + Secrete – Oris regio : Angioedema + in the upper lip Extremitas sinistra Regio Multiple urticaria with variable size and shape, diameter +/- 1,5 – 3 cm and multiple red macules unsharply marginated with variable size Fitzpatrick 9 th edition

Theory In My Case Angio-oedema of the lip (a) during and (b) 3 days after an attack. (Courtesy of St John’s Institute of Dermatology, London, UK.)

Theory In My Case Fitzpatrick 9 th edition

Theory In My Case Sex: Female Age: 40 years old History of >5 years Myesthenia Gravis (since 2006) and regularly take medication Fitzpatrick 9 th edition, Bansel, 2019

Theory In My Case History of >5 years Myesthenia Gravis (since 2006) Mysthenia Gravis is autoimmune disease is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest.  Bradykinin also plays a role in urticaria. Increased bradykinin itself has been found to be the underlying mechanism for angioedema Myasthenia Gravis: A Review. Autoimmune Diseases, 2014

Theory In My Case Fitzpatrick 9 th edition, PPK Sutomo Stop all suspected drugs 2.Dipenhidramine HCl 3 x 10 mg IM  cetirizine 2x10mg per oral 3.Dexametason 0,5mg 3x1

THANK YOU

Case Report: Resolution of chronic urticaria following treatment of odontogenic infection A number of studies have shown an increased prevalence of oropharyngeal infections including dental infections, sinusitis and tonsillitis in patients with chronic urticaria. An early study from 1964 showed radiological evidence of focal tooth infection in 29% of their cohort of patients with chronic urticaria. In one case a bacterial culture of a tooth lesion grew gram-negative bacteria Veillonella parvula It is thought that Lipopolysaccharide from gram-negative bacteria induces an inflammatory response characterized by the release of histamine from mast cells and causes urticaria.

Urticaria and Angioedema. Fitzpatrick’s Dermatology in General Medicine 9 th ed

The use of first-generation sedative antihistamines in infants and children is strongly discouraged by most consensus reviews. Cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine have been well studied in children, and their long-term safety has been well established in the paediatric population. Hence, these drugs with proven efficacy and established long-term safety in paediatric population are recommended. Furthermore, further selection is also dependent upon available formulations, which are suitable for children. Key concepts of urticaria management in children are: 1.Elimination of underlying causes and/or eliciting triggers wherever possible 2.Second-generation H1-antihistamines are the mainstay of treatment aimed at providing symptom relief. The safety of up-dosing has not been validated in children. First-generation H1-antihistamines should be avoided 3.Difficult cases may require other therapeutic interventions, the risk- benefit ratio being carefully analysed, as there is a paucity of supporting evidence 4.Corticosteroids should be avoided and if used, should strictly be limited for short periods only (3–7 days).

Classification of Urticarias 1 1. Adapted from: Zuberbier T, et al. Allergy 2014;69 (7):868–87. Chronic spontaneous urticaria Chronic Acute Spontaneous Inducible Urticaria Known causes (including autoimmunity, infection, food components, etc) Unknown causes Chronic spontaneous urticaria (CSU) can be defined as the spontaneous daily, or almost daily, occurrence of itchy hives, angioedema or both, due to known or unknown causes, and lasting for 6 weeks or more Symptoms daily or almost daily for ≥6 weeks No obvious external specific trigger Symptoms for <6 weeks Symptoms induced by a specific trigger, e.g. temperature, pressure, cholinergic New 2013

The Urticaria Activity Score (UAS) The UAS is a validated daily measure, encompassing hives and itch, to assess urticaria severity and monitor treatment outcomes (Zuberbier et al., 2018; Młynek et al., 2008 The daily UAS (range, 0-6) equals the sum of daily Itch Severity Score (ISS) and the hives score The UAS7 (range, 0-42) is a weekly composite of the daily UAS and is used to measure disease activity over 7 days

UAS7 is a measure of CSU severity over 7 days (Zuberbier et al., 2018; Maurer et al., 2011) A variation of the UAS7, the UAS7 TD was recently assessed to determine whether the UAS7 could be used to divide patients into subgroups to better assess impact on quality of life. It was found that categorical UAS7 subgroups could be used to predict differences among patients with different levels of disease severity – this may enable better clinical monitoring of treatment efficacy (Stull et al., 2017).

Urtikaria dingin adalah urtikaria fisik yang ditandai dengan munculnya bintil dan suar sebagai tanggapan menjadi dingin. Dalam kebanyakan kasus, kulit lokal bersentuhan dengan flu substansi menginduksi bintil dan suar di area dingin kontak (urtikaria kontak dingin). Penampilan kulit bintil dan suar biasanya datar dan lebar menyebar tetapi mungkin juga belang-belang. Gatal dan bintik kulit terjadi dalam beberapa menit dan bertahan hingga 1 jam. Dalam kasus yang parah, mulut dan faring mungkin membengkak setelah minum cairan dingin. Penderita fluurtikaria juga dapat mengembangkan gejala anafilaksis, termasuk palpitasi, sakit kepala, mengi, dan kehilangan Cold urticaria is a marked physical urticaria with nodules and flares appearing in response become cold. In most cases, local skin comes in contact with flu substance induces nodules and flares in cold areas contact (cold contact urticaria). Skin appearance nodules and flares are usually flat and wide spread but may also be punctate. Itching and freckles skin occurs within minutes and lasts up to1 hour. In severe cases, possible mouth and pharynx swells after drinking cold liquids. Flu sufferers urticaria can also develop symptoms of anaphylaxis, including palpitations, headaches, wheezing, and loss

In rare cases, erythematous edematous and deep swelling may appear 9 to 18 hours after cold challenge (delayed cold urticaria)

Heat urticaria is a rare subtype of physical urticaria characterized by wheals and flare that develop within minutes after local heat exposure to the skin and disappear within a few hours at the longest (see Fig. 41-1D). In contrast to cholinergic urticaria that involves small punctate eruptions in response to conditions that elicit sweating, patients with heat urticaria develop wheals and flare that spread in the area of skin exposed to heat, regardless of the core body temperature or sweating. Heat urticaria adalah subtipe fisik urtikaria yang langka ditandai dengan bintil dan suar yang berkembang di dalammenit setelah kulit terpapar panas lokal dan menghilang dalam beberapa jam paling lama (lihat Gambar 41-1D). Berbeda dengan urtikaria kolinergik yang melibatkan kecil letusan belang-belang sebagai respons terhadap kondisi yang ditimbulkan berkeringat, pasien dengan urtikaria panas mengembangkan bintil dan flare yang menyebar di area kulit yang terkena panas, terlepas dari suhu inti tubuh atau keringat.

Solar urticaria is a rare subtype of physical urticaria characterized by wheals and flare that develop within minutes after local exposure of the skin to certain wavelengths of light. The urticarial lesions usually resolve within hours but may accompany headache, syncope, dizziness, wheezing, and nausea. The shape of skin eruptions in solar urticaria is consistent with the area exposed to the light of an eliciting wavelength. There may be widespread wheals, flare, or punctate redness but not the small wheals observed in cholinergic urticaria. The face and hands may develop fewer lesions than skin areas that are usually covered by clothes because of hardening due to chronic exposure to sunlight Solar urticaria adalah subtipe fisik urtikaria yang langkaditandai dengan bintil dan suar yang berkembang di dalambeberapa menit setelah kulit terpapar pada panjang gelombang tertentu cahaya. Lesi urtikaria biasanya sembuhdalam beberapa jam tetapi mungkin menyertai sakit kepala, sinkop,pusing, mengi, dan mual. Bentuk erupsi kulit di urtikaria matahari konsisten dengan area yang terpaparke cahaya dari panjang gelombang yang muncul. Mungkin disana bintil-bintil yang menyebar luas, kambuh, atau kemerahan yang tajam tetapi tidak bintik kecil yang diamati pada urtikaria kolinergik. Itu wajah dan tangan mungkin mengembangkan lebih sedikit lesi daripada kulitdaerah yang biasanya tertutup pakaian karenapengerasan karena paparan sinar matahari kronis

Delayed pressure urticaria is characterized by deep dermal wheals that appear in a continuously compressed region with a latency of 30 minutes or several hours after the release of the compression. The wheals last for several hours or up to 3 days and may be accompanied by a burning sensation or pain rather than the itching often seen with CSU. DPU may develop by itself but may often be accompanied by CS Urtikaria tekanan tertunda ditandai dengan dermal dalam wheals yang muncul secara terus menerus dikompresi wilayah dengan latensi 30 menit atau beberapa jam setelah rilis kompresi. Bintik terakhir beberapa jam atau hingga 3 hari dan dapat disertai dengan sensasi terbakar atau nyeri daripada gatal sering terlihat dengan CSU.50 DPU dapat berkembang dengan sendirinya tetap mungkin sering disertai dengan CS

Contact urticaria is classified as an induced subtype urticaria is characterized by an immediate development wheal reactions and flares at the site of contact with certain substances. Can be immunological (IgE mediated) or nonimmunologically. Whales and flares usually shows up in 30 minutes and is done disappears within a few hours and may also develop to generalized urticaria and even anaphylaxis. Cold urticaria, heat urticaria, and aquagenic urticaria are also caused by contact with a suitable substance physical characteristics but usually aren’t fall into this category. The case where oral edema and discomfort is the main symptom, which is caused by contact of the oral mucosa with certain foods, moderate referred to as oral allergy syndrome (OAS). Urtikaria kontak diklasifikasikan sebagai subtipe yang diinduksi urtikaria ditandai dengan perkembangan segera reaksi wheal dan suar di lokasi kontak dengan zat tertentu. Bisa imunologis (IgE dimediasi) atau nonimunologis. Paus dan suar biasanya muncul dalam 30 menit dan selesai menghilang dalam beberapa jam dan mungkin juga berkembang untuk urtikaria umum dan bahkan anafilaksis. Dingin urtikaria, urtikaria panas, dan urtikaria aquagenik adalah juga disebabkan oleh kontak dengan bahan yang sesuaikarakteristik fisik tetapi biasanya tidaktermasuk dalam kategori ini. Kasus dimana edema oraldan ketidaknyamanan adalah gejala utama yang disebabkan olehkontak mukosa mulut dengan makanan tertentu, sedangdisebut sebagai sindrom alergi oral (OAS).