scholarly journals Successful Desensitization of a Patient with Aplastic Anemia to Antithymocyte Globulin

2015 ◽  
Vol 6 (1) ◽  
pp. ar.2015.6.0110 ◽  
Author(s):  
Stephanie A. Wolanin ◽  
Jeffrey G. Demain ◽  
Eric A. Meier
Keyword(s):  
Aplastic Anemia ◽  
Skin Test ◽  
Antithymocyte Globulin ◽  
Skin Testing ◽  
Serum Sickness ◽  
Literature Discussion ◽  
Type I ◽  
Life Threatening ◽  
Delayed Reactions ◽  
Type I Hypersensitivity

Antithymocyte globulin (ATG) is a polyclonal gamma immunoglobulin derived from either rabbit or equine serum that serves as therapy for aplastic anemia; however, ATG causes serum sickness in up to 70% and anaphylaxis in up to 5% of recipients. Intradermal (ID) skin testing has been the primary technique used to evaluate for a preexisting Gell and Coombs type I hypersensitivity reaction to ATG. There are no data reporting the predictive value of delayed reactions to ID testing on the risk of serum sickness. This study was designed to establish the importance of epicutaneous and ID skin testing before the administration of ATG through a case report and literature discussion. We report a patient with severe aplastic anemia that was successfully desensitized to ATG after a negative epicutaneous skin test and positive ID skin test. The patient had neither systemic nor localized reactions during the desensitization. Desensitization to ATG in patients with positive epicutaneous skin testing has been shown to be associated with serious and potentially life-threatening complications and should only be considered when the benefits outweigh the risks. Epicutaneous skin testing should be considered in conjunction with ID skin testing when screening for potential sensitivity to ATG. Because of the serious risk of anaphylaxis, desensitization should be performed in an intensive care unit setting in conjunction with a physician familiar with drug desensitization and the management of anaphylaxis.

Skin Tests in the Diagnosis of Allergic Conditions

1981 ◽  
Vol 2 (10) ◽  
pp. 327-332
Author(s):  
Lillian P. Kravis
Keyword(s):  
Skin Test ◽  
Skin Testing ◽  
Clinical History ◽  
Skin Tests ◽  
Food Allergies ◽  
Type I ◽  
Test Results ◽  
Type Iv ◽  
Transfer Testing ◽  
Allergic Disorders

Allergic disorders may be classified into four main categories of immunologic hypersensitivity reactions: type I, immediate or anaphylactic; type II, cytotoxic; type III, involving immune complexes; and type IV, delayed or cell mediated. Type I reactions are those most commonly encountered in clinical allergy. They may be well defined by skin testing, provided the patients to be tested are carefully selected and the tests are applied properly and interpreted critically. Major indications for direct skin testing are: (1) to separate atopic from nonatopic patients; (2) to help in identifying specific allergens in atopic persons; and (3) to reassess the allergic profile in patients receiving immunotherapy. Other indications for skin-testing, of more limited applicability, include: (1) screening for hypersensitivity to vaccines; (2) testing for reactivity to drugs (and particularly penicillin); (3) testing for immediate and delayed reactions in such conditions as bronchopulmonary aspergillosis; and (4) in evaluation of patients with reactions to insect stings. Skin-testing has limited usefulness in early infancy, in chronic urticaria, in the investigation of food allergies, in atopic dermatitis not accompanied by other manifestations of atopy, or in allergic reactions to drugs other than penicillin. A checklist to be consulted prior to performing or interpreting skin tests should include: (1) assurance of the potency of the extract used in testing; (2) knowledge of the nonspecific irritant properties of any extracts used for testing; (3) history of administration of antihistamine drugs or epinephrine prior to testing; and (4) the correlation of skin test results with clinical history. The help of a qualified allergist should be sought if: (1) skin test results are at variance with the historical data; or (2) systemic reactions are induced by skin testing; or (3) the patient fails to respond to the therapy dictated by the skin test results. Alternatives or supplements to skin-testing include RAST testing and measurement of histamine release from sensitized leukocytes. These have rendered passive transfer testing (PK or Prausnitz-Küstner) substantially obsolete. Direct allergy skin testing remains the most sensitive, most specific, and most reliable method presently available to the physician for investigation of IgE-mediated allergic disorders.

Serum Sickness and Plasma Cytokine Profiles After Treatment with Antithymocyte Globulin In Severe Aplastic Anemia Patients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1162-1162
Author(s):  
Xingmin Feng ◽  
Phillip Scheinberg ◽  
Olga Nunez ◽  
Angelique Biancotto ◽  
Tomoiku Takaku ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Conflicts Of Interest ◽  
Late Phase ◽  
Phase Response ◽  
Serum Sickness ◽  
Severe Aplastic Anemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cytokine Profiles ◽  
Antibody Titers

Abstract Abstract 1162 Antithymocyte globulin (ATG) is the standard therapy for severe aplastic anemia (SAA). Currently, two different preparations are commercially available, produced in horse and rabbit. As foreign proteins, ATGs elicit immune response in humans. Foreign antigen and responding antibody form circulating immune complexes that may deposit in tissues and cause serum sickness (SS), usually around day 10 after initiation of ATG therapy. The relationship of human anti-ATG antibodies with SS and the cytokine profiles of ATG-treated patients are not defined. We studied human anti-ATG antibody titers and 27 cytokines in the plasma of 27 patients who received horse ATG (hATG) and 25 patients who received rabbit ATG (rATG) for SAA. Cyclosporine was administered with both ATGs to achieve trough levels of 200–400 ng/mL. Plasma samples were obtained at: baseline pre-treatment, weekly in the first month, and at 3 and 6 months after ATG treatment. Nine of 25 (36%) rATG recipients and 5 of 27 (19%) hATG recipients developed SS at about week two. When measured by enzyme-linked immunosorbent assay, human anti-hATG or rATG antibody titers peaked during weeks 2–3, and then declined at month 2, reducing to baseline levels at month 6. All 9 rATG-treated patients who developed SS had significantly higher antibody titers at week 2 than did 16 rATG-treated patients without SS (O.D. 1.704 ± 0.173 vs 0.664 ± 0.076, p < 0.0001), a difference also presented at month 3 (p = 0.002). In hATG-treated patients, human anti-hATG antibody titers did not appear to correlate with the occurrence of SS. We measured cytokines using a 27-plex cytokine magnetic bead-based Luminex assay. Both hATG and rATG-treated patients without SS showed similar cytokine profiles: a peak in MIP-1β, IL-8, IL-10, IL-13, G-CSF and IP-10 at day 2, which rapidly declined to baseline; this early-phase response may be the direct effect of ATG infusion. In rATG-treated patients, SS patients had significantly higher plasma levels of IFNγ, IL-1ra, IL-12 (p < 0.0001), IL-4, IL-1β (p = 0.0001), IL-6 (p = 0.0002), IL-10 (p = 0.0003), IL-17, GM-CSF, FGFb (p = 0.0015), IL-15, MIP-1α (p = 0.0046), PDGF (p = 0.0052), IL-13 (p = 0.0066), and IL-2 (p = 0.0077) than did non-SS patients at weeks 2 and 3; this late-phase response may be secondary to heterologous antibodies to rATG. In conclusion, human anti-ATG antibodies were frequently detected after ATG administration; antibody titers associated with SS in rATG-treated patients; and SS patients and non-SS patients showed broadly distinct cytokine profiles. Disclosures: No relevant conflicts of interest to declare.

Management of the refractory aplastic anemia patient: what are the options?

Blood ◽  
2013 ◽  
Vol 122 (22) ◽  
pp. 3561-3567 ◽  
Author(s):  
Judith C. W. Marsh ◽  
Austin G. Kulasekararaj
Keyword(s):  
Supportive Care ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Unrelated Donor ◽  
Refractory Disease ◽  
Centers Of Excellence ◽  
Hematopoietic Stem ◽  
Haploidentical Transplantation ◽  
Life Threatening ◽  
Matched Donor

Abstract Refractory aplastic anemia (AA) is defined as a lack of response to first-line immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and is manifested as persistence of severe cytopenias at 6 months after IST. Although supportive care is critical for AA patients, it is of paramount importance for refractory disease in view of the longer duration of pancytopenia and susceptibility to life-threatening infections due to IST. Improvements in supportive care have largely contributed to better outcome over the past 2 decades, with 5-year overall survival reaching 57% during 2002 to 2008 for patients with AA unresponsive to initial IST. Exclusion of hypocellular myelodysplastic syndrome and constitutional BM failure masquerading as apparent idiopathic AA should be done in conjunction with centers of excellence. Hematopoietic stem cell transplantation is indicated if refractory AA patients are fit and have a suitably matched donor, either a sibling (>40-50 years) or unrelated donor. Patients lacking a fully matched donor should be considered for a second course of antithymocyte globulin plus cyclosporin, although response in the refractory setting is only ∼30% to 35%. Response may also occur with alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA. The emerging data for alternate donor (cord or haploidentical) transplantation in AA has provided additional therapeutic choices to consider in refractory disease.

Management of the refractory aplastic anemia patient: what are the options?

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Judith C. W. Marsh ◽  
Austin G. Kulasekararaj
Keyword(s):  
Supportive Care ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Unrelated Donor ◽  
Refractory Disease ◽  
Centers Of Excellence ◽  
Hematopoietic Stem ◽  
Haploidentical Transplantation ◽  
Life Threatening ◽  
Matched Donor

Abstract Refractory aplastic anemia (AA) is defined as a lack of response to first-line immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and is manifested as persistence of severe cytopenias at 6 months after IST. Although supportive care is critical for AA patients, it is of paramount importance for refractory disease in view of the longer duration of pancytopenia and susceptibility to life-threatening infections due to IST. Improvements in supportive care have largely contributed to better outcome over the past 2 decades, with 5-year overall survival reaching 57% during 2002 to 2008 for patients with AA unresponsive to initial IST. Exclusion of hypocellular myelodysplastic syndrome and constitutional BM failure masquerading as apparent idiopathic AA should be done in conjunction with centers of excellence. Hematopoietic stem cell transplantation is indicated if refractory AA patients are fit and have a suitably matched donor, either a sibling (> 40-50 years) or unrelated donor. Patients lacking a fully matched donor should be considered for a second course of antithymocyte globulin plus cyclosporin, although response in the refractory setting is only ∼ 30% to 35%. Response may also occur with alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA. The emerging data for alternate donor (cord or haploidentical) transplantation in AA has provided additional therapeutic choices to consider in refractory disease.

scholarly journals Immediate allergic reaction to methylprednisolone with tolerance of other corticosteroids

2012 ◽  
Vol 140 (3-4) ◽  
pp. 233-235 ◽  
Author(s):  
Marina Atanaskovic-Markovic ◽  
Marija Gavrovic-Jankulovic ◽  
Srdja Jankovic ◽  
Gordan Blagojevic ◽  
Tanja Cirkovic-Velickovic ◽  
...  
Keyword(s):  
Allergic Reaction ◽  
Anaphylactic Reaction ◽  
Skin Testing ◽  
Cross Reactivity ◽  
Clinical Findings ◽  
Skin Tests ◽  
Type I ◽  
Positive Skin ◽  
Uncommon Case ◽  
Type I Hypersensitivity

Introduction. In spite of the wide usage of corticosteroids for the treatment of a plethora of diseases, sometimes they can induce immediate hypersensitivity reactions, which are however uncommon. Case Outline. We report a case of immediate allergic reaction induced by intravenous methylprednisolone given before operation for surgical repair of an arm contracture as a sequel of burns, which the child had tolerated a month before. Six weeks later the patient repeated the anaphylactic reaction during skin testing to methylprednisolone. In addition, basophile activation test with methylprednisolone (BAT) was positive. Conclusion. This case report describes a patient who experienced intraoperative anaphylaxis and anaphylactic reaction induced by skin testing. This is the first report on induction of both anaphylactic reactions by methylprednisolone in the same child. Clinical findings, positive BAT and positive skin tests with methylprednisolone imply that the child developed type-I hypersensitivity. The lack of cross-reactivity with other corticosteroids emphasizes that the reactions were caused by the steroid molecule.

Response to Immunosuppressive Therapy with Antithymocyte Globulin (ATG) In Older Patients with Aplastic Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4374-4374
Author(s):  
Biju George ◽  
Vikram Mathews ◽  
Kavitha M Lakshmi ◽  
Rayaz Ahmed ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Older Patients ◽  
Antithymocyte Globulin ◽  
Conflicts Of Interest ◽  
Age Groups ◽  
Older Age ◽  
Serum Sickness ◽  
Age Group ◽  
Number Of Patients

Abstract Abstract 4374 Immunosuppressive therapy (IST) with antithymocyte globulin in combination with prednisolone and cyclosporine is the treatment of choice for patients with aplastic anemia who are ineligible for transplant either because of age or because of absence of a HLA identical donor. Limited data that exists on the role of immunosuppressive therapy in older patients with aplastic anemia suggest that responses were poorer. This retrospective analysis was aimed at determining whether older patients with aplastic anemia had an inferior response to IST compared with younger patients. Between October 1985 to December 2010, 322 adult patients (>12 years) were treated at our centre with antithymocyte globulin (ATG) in combination with prednisolone and with/without cyclosporine. Either ATGAM (Pharmacia Upjohn, USA) at 40 mg/kg/day × 4 days or Lymphoglobulin (Pasteur Merieux, France) at 15 mg/kg/day × 5 days was used. Prednisolone at 1 mg/kg in 3 divided doses were started one day after completion of ATG and tapered from Day +14 if there was no evidence of serum sickness. Cyclosporine at the dose of 6 mg/kg/day in 2 divided doses was started once steroids were tapered and then continued for 12 months and then tapered depending upon response. Patients were divided into 3 age groups - Ages 12 – 29 [n=116], ages 30 – 49 [n = 116] and > 50 years [n = 90]. The baseline characteristics are detailed in the table below – Thirty one patients were above the age of 60 years. The older age group had significantly higher % of males, more use of ATGAM compared with Lymphogloblin and a higher number was given Cyclosporine (CSA) post ATG. The severity of aplastic anemia (severe vs non-severe) and the median time from diagnosis to administration of ATG was not significantly different between the 3 groups. The number of patients who developed serum sickness was significantly lower in the older age group (21.1%) compared to the age group of 30 – 49 (35.3%) and 12 – 29 years (48.3%) [p = 0.000]. The overall response to ATG was similar in all 3 groups (63.8% in age 12 –29, 64.7% in ages 30 – 49 and 54.4% in age > 50 yrs) [p = 0.233]. The response in patients above the age of 60 years was 51.6%. Six patients received a second course of ATG while 3 patients underwent HLA identical sibling donor transplantation. At a median follow up of 32 months (range: 1 –145), 221 patients (68.6%) are alive. The overall survival is similar for the older age group compared with the younger age groups (66.7% with age>50 years, 68.1% with age 30–49 and 70.7% with age 12 –29) [p= 0.817]. In conclusion, immunosuppressive therapy with ATG has a reasonable outcome in older patients (> 50 years) with aplastic anemia.Table 1:Demographic characteristics and outcome of IST among the 3 age groupsVariables12 – 29 yrs (n = 116)30 – 49 yrs (n = 116)>50 yrs (n = 90)p valueMale84 (72.4%)87 (75%)52 (57.8%)Female32 (27.6%)29 (25%)38 (42.2%)0.019Severity of AA86 (74.1%)77 (66.4%)63 (70%)0.581VSAA + SAA30 (25.9%)39 (33.6%)27 (30%)NSAAType of ATG45 (38.8%)33 (28.4%)53 (58.9%)0.000ATGAM71 (61.2%)83 (71.6%)37 (41.1%)LymphoglobulinCSA used92 (79.3%)103 (88.8%)85 (94.4%)0.005Yes24 (20.7%)13 (11.2%)5 (5.6%)NoResponse74 (63.8%)75 (64.6%)49 (54.4%)0.233Overall response34 (29.3%)28 (24.1%)15 (16.7%)Complete response (CR)40 (34.5%)47 (40.5%)34 (37.8%)Partial response (PR)42 (36.2%)41 (35.3%)41 (45.6%)No response (NR)Overall survival82 (70.7%)79 (68.1%)60 (66.7%)0.817Alive34 (29.3%)37 (31.9%)30 (33.3%)Dead Disclosures: No relevant conflicts of interest to declare.

Serum Sickness and Severe Acute Renal Failure After Rabbit Antithymocyte Globulin Treatment in Aplastic Anemia

2011 ◽  
Vol 33 (1) ◽  
pp. 43-46 ◽  
Author(s):  
Paulo Sérgio Lucas da Silva ◽  
Roselene Mesquita Augusto Passos ◽  
Daniel Reis Waisberg ◽  
Miriam Verônica Flor Park
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Serum Sickness ◽  
Rabbit Antithymocyte Globulin

Hypersensitivity reactions to paclitaxel: The Mexican experience of rapid desensitization

2021 ◽  
pp. 107815522110085
Author(s):  
Rosalaura V Villarreal González ◽  
Sandra N González Díaz ◽  
Rodrigo A de la Cruz Cruz ◽  
Oscar Vidal Gutiérrez ◽  
Cindy E de Lira Quezada
Keyword(s):  
Adverse Drug Reactions ◽  
Skin Testing ◽  
Mexican Population ◽  
High Rate ◽  
Severe Reaction ◽  
Type I ◽  
Hypersensitivity Reactions ◽  
Drug Reactions ◽  
12 Steps ◽  
Type I Hypersensitivity

Background Taxanes adjuvant therapy is recommended in certain high risk or metastatic tumors, particularly in lung and breast cancer, but also in other types of cancer like ovarian. The incidence of severe adverse drug reactions to paclitaxel is of approximately 10%. Objectives Analyze type I hypersensitivity reactions to paclitaxel and their management in the Mexican population. Method It is a retrospective, observational and descriptive study that included type I hypersensitivity reactions to paclitaxel reported from our database. Symptoms of hypersensitivity reactions to paclitaxel were classified and skin testing was performed with a 6 mg/mL paclitaxel concentration. The desensitization procedure consisted of a 12-steps, 3-bags of 250 mL protocol with a 6–7-hour duration. Results A total of 60 desensitization procedures were performed and were all completed successfully. All participants in our group were female, their median age was 44.5 years. All of our patients had hypersensitivity adverse drug reaction to paclitaxel during their first exposure and within the first 10 minutes of infusion. 63.6% of the patients had a moderate hypersensitivity reaction to paclitaxel and 36.4% had a severe reaction. Conclusions Paclitaxel continues to be a common use drug and has a high rate of adverse drug reactions. This is the first study of hypersensitivity to paclitaxel in a Mexican population.

scholarly journals Immunological Basis for the Development of Allergic Diseases-Prevalence, Diagnosis and Treatment Strategies

2021 ◽  
Author(s):  
Siddanakoppalu N. Pramod
Keyword(s):  
Mast Cells ◽  
White Blood Cells ◽  
Treatment Strategies ◽  
Allergic Diseases ◽  
Specific Ige ◽  
Type I ◽  
Severe Condition ◽  
Life Threatening ◽  
Cross Links ◽  
Type I Hypersensitivity

Allergy is an immune disorder due to over responsiveness of immune system to a relatively normal and harmless antigen; derived from environmental and dietary substances commonly referred as allergens. Allergy is an IgE mediated type I hypersensitivity which is characterized by the degranulation of specialized white blood cells known as mast cells and basophils. Majority of characterized allergens are proteinaceous in nature and induce Th2 response. Specific Th2 cytokines elicit the induction of allergen specific IgE antibodies in sensitive individuals. The IgE binds to Fc epsilon receptor on basophil/mast cells and on exposure, allergens cross links the IgE and induce release of hypersensitivity mediators that result in allergic symptoms. The symptoms varies from mild allergies like hay fever, itchiness, rashes, rhinatisis, conjunctivitis to a severe condition such as Asthma and some time life threatening anaphylaxis. At present a various blood based test exist to diagnose allergies which include skin prick, patch test and Specific IgE tests. The best treatment available is to avoid exposure to allergens alternatively use of anti-histamines, steroids or other symptom reducing medications are in practice. Immunotherapy to desensitize the response to allergen and targeted therapy are promising for allergy in future.

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