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Histopathological features. Vacuolar degeneration of the dermoepidermal junction and a superficial perivascular inflammation with lymphocytes and sparse eosinophils (hematoxylin–eosin, original magnification ×200).
Source publication
Pegylated or non-pegylated α-interferon are frequently used medications for the treatment of both chronic hepatitis B and chronic hepatitis C. Skin disorders, which are mainly comprised of eczematous dermatitis, are frequently seen during treatment with this drug. However, drug eruption or morbilliform eruptions due to interferons have been rarely...
Context in source publication
Context 1
... after the seventh dose of PEG-IFN-a-2a, the same rash reappeared on her back. We performed skin biopsy to confirm the early diagnosis of morbilliform drug eruption. Histology of the skin specimen revealed vacuolar degeneration of the dermoepidermal junction and a superficial peri- vascular inflammation with lymphocytes and sparse eosinophils (Fig. 2). These clinicopathological fea- tures were consistent with morbilliform drug eruption. We stopped the PEG-IFN treatment and switched to conventional IFN-a-2a three times weekly. Skin lesions showed complete regression within 1 week, and the topical steroid was stopped. Lesions did not reappear under treatment with non-pegylated ...
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Since the discovery of HBsAg in the early 1960s, presence of HBsAg in serum has only served to diagnose hepatitis B. Recent development in the quantitative measurement of serum HBsAg has enabled us to improve our understanding on the management of chronic hepatitis B. The surface antigen (sAg) level is at its highest in immune tolerance phase and d...
Citations
... Cutaneous hypersensitivity reactions have been frequently reported for interferons, and for peginterferon alpha-2b especially, and they have been extensively described in the literature [24][25][26][27][28][29]. A large body of evidence suggests that cutaneous hypersensitivity reactions are more frequent for peginterferon alpha as compared with its non-PEGylated form [28][29][30] and that switching from peginterferon alpha to conventional interferon alpha decreases the risk of severe allergic cutaneous reactions [30][31][32], suggesting that the likely culprit for the skin reaction may be the PEG component of peginterferon [30][31][32]. Additionally, pegaspargase was significantly associated with an increased reporting of hypersensitivity reactions. ...
... Cutaneous hypersensitivity reactions have been frequently reported for interferons, and for peginterferon alpha-2b especially, and they have been extensively described in the literature [24][25][26][27][28][29]. A large body of evidence suggests that cutaneous hypersensitivity reactions are more frequent for peginterferon alpha as compared with its non-PEGylated form [28][29][30] and that switching from peginterferon alpha to conventional interferon alpha decreases the risk of severe allergic cutaneous reactions [30][31][32], suggesting that the likely culprit for the skin reaction may be the PEG component of peginterferon [30][31][32]. Additionally, pegaspargase was significantly associated with an increased reporting of hypersensitivity reactions. ...
Background and objective:
Evidence highlights the allergenic potential of PEGylated drugs because of the production of anti-polyethylene glycol immunoglobulins. We investigated the risk of hypersensitivity reactions of PEGylated drugs using the Italian spontaneous adverse drug reaction reporting system database.
Methods:
We selected adverse drug reaction reports attributed to medicinal products containing PEGylated active substances and/or PEGylated liposomes from the Italian Spontaneous Reporting System in the period between its inception and March 2021. As comparators, we extracted adverse drug reaction reports of medicinal products containing the same non-PEGylated active substances and/or non-PEGylated liposomes (or compounds belonging to the same mechanistic class). A descriptive analysis of reports of hypersensitivity reactions was performed. Reporting rates and time to onset of hypersensitivity reactions were also calculated in the period between January 2009 and March 2021. As a measure of disproportionality, we calculated the reporting odds ratio.
Results:
Overall, 3865 adverse drug reaction reports were related to PEGylated medicinal products and 11,961 to their non-PEGylated comparators. Around two-thirds of patients were female and reports mostly concerned patients aged between 46 and 64 years. The frequency of hypersensitivity reactions reporting was higher among PEGylated versus non-PEGylated medicinal products (11.7% vs 9.4%, p < 0.0001). The hypersensitivity reaction reporting rates were higher for PEGylated medicinal products versus non-PEGylated medicinal products, with reporting rate ratios that ranged from 1.4 (95% confidence interval 0.8-2.5) for pegfilgrastim versus filgrastim to 20.0 (95% confidence interval 2.8-143.5) for peginterferon alpha-2a versus interferon alpha-2a. The median time to onset of hypersensitivity reactions was 10 days (interquartile range: 0-61) for PEGylated medicinal products, and 36 days (interquartile range: 3-216) for non-PEGylated comparators. Statistically significant reporting odds ratios were observed when comparing the reporting of hypersensitivity reactions for PEGylated versus non-PEGylated medicinal products (reporting odds ratio: 1.3; 95% confidence interval 1.1-1.4). However, when using all other drugs as comparators, the disproportionality analysis showed no association with hypersensitivity reactions for PEGylated nor non-PEGylated medicinal products, thus suggesting that many other triggers of drug-induced hypersensitivity reactions play a major role.
Conclusions:
The findings of this analysis of the Italian spontaneous adverse drug reaction database suggest a potential involvement for PEGylation in triggering drug-related hypersensitivity reactions, especially clinically relevant reactions. However, when comparing both PEGylated and non-PEGylated drugs under study to all other drugs no disproportionate reporting of hypersensitivity reactions was observed, probably due to a masking effect owing to the presence in the same database of other medicinal products increasing the threshold required to highlight a safety signal when the entire database is used as a reference.
... However, the relationship between eczematous symptoms and the pegylated form suggests sensitization to polyethylene glycol [80]. These data are consistent with similar findings from other published reports [81,82]. None of these studies makes reference to an allergy workup. ...
Strictly speaking, biological drugs are defined as drugs obtained using biotechnology that act on the immune system. They encompass monoclonal antibodies, fusion proteins, and cytokines. Although they are restricted to specific diseases, they have been increasingly used in recent years, with the consequent reporting of adverse reactions, many of which occur during the postmarketing phase. Because of the characteristics of adverse reactions, a new classification has been proposed. Hypersensitivity reactions are beta-type reactions and include infusion reactions and injection site reactions. In some cases, an immune mechanism mediated by IgE, IgG, or T cells is involved. Clinical symptoms vary widely, from skin reactions to anaphylaxis. Diagnostic studies are based on skin tests and in vitro tests (specific IgE, basophil activation test). Most are not standardized and are conducted in small groups of patients, thus making it impossible to obtain sensitivity and specificity values. With some biological drugs, desensitization protocols have proven successful. In this review, we discuss hypersensitivity reactions to biological drugs and the diagnostic tests used to assess these reactions.
... A side effect of the immunomodulatory action of interferon is the possible triggering or exacerbation of psoriasis [12,13] . Several reports in the literature have suggested a possible association between PEG-IFN-α therapy, sarcoidosis and morbilliform eruptions [14][15][16][17] . However, cutaneous drug reactions are more common with PEG-IFN-α 2a plus ribavirin combination therapy [6][7][8][9] . ...
Pityriasis rosea (PR) is an acute, self-limiting exanthematous disease caused by the endogenous reactivation of human herpesvirus (HHV)-6 and/or HHV-7 infection in conditions of altered immunity. In addition, many drugs have been incriminated as possible triggers of PR-like eruptions, characterized by clinical, morphological and histopathological features that differ from typical PR. Here, we report a case of PR in a patient with chronic hepatitis B, receiving pegylated interferon α2a (PEG-IFN-α2a). PR, arising after the second administration of the PEG-IFN-α2a, might be considered a clinical expression of the patient's altered immune condition as reported in the immune reconstitution inflammatory syndrome affecting patients with human immunodeficiency virus infection after high-dose antiretroviral therapy. © 2013 S. Karger AG, Basel.
... Apart from the almost invariable occurrence of an erythematous roundish plaque at the injection site (Figure 17), administration of INF in HBV patients has been implicated in the following undesired effects (Table 5): skin necrosis at the injection site [110], angioedemaurticaria syndrome [111], diffuse patchy erythematous rash [112], morbilliform exanthema [113], psoriasis [114,115], vitiligo [115], lichen planus [116], ocular trichomegaly [117]. ...
It is undisputable that a multifaceted biological interplay exists between the skin and the liver. The integument can firstly be viewed as a ‘gate’ through which hepatotropic viruses may access the blood stream. In this respect, one may think of the huge number of B and C virus hepatites that must have been acquired in a more or less distant past due to either intravenous drug consumption, use of contaminated equipment in beauty and health care-related procedures, or even dermal tattooing. Moreover, one may consider that some cases of herpes simplex virus hepatitis have been reported in the literature which are not unlikely ascribable to systemic dissemination from primary muco-cutaneous lesional foci.
Yet, the skin may also be viewed as a ‘mirror’ capable of projecting on the body surface more or less specific echoes of disease conditions involving the liver. A recent review of the issue by Hazin and coworkers is introduced by the following simple but just as brilliant statement: “Dysfunction in the body’s second largest organ, the liver, often yields changes in the body’s largest organ, the skin”. The most trivial paradigm sustaining such an obvious assumption is jaundice when it is sustained by primary failure of hepatocytes to perform one of their main functions, that is to conjugate bilirubin into a secretable form. However, further and less obvious paradigms, such as cutaneous manifestations of mixed cryoglobulinemia in HCV infected patients, will also be discussed.
Since the issue that will be specifically reviewed in this chapter is all the many possible links between skin and virus-induced liver disease, this introductory framework is to be completed by mentioning the not unusual circumstances in which neither the skin nor the liver disease in itself, but treatments undertaken to cure a disease of one of the two organs may have undesired consequences on the other one. This seems obviously true thinking of some doubleedged risky circumstances in which either worsening of psoriasis in patients undergoing interferon plus ribavirin therapy, or reactivation of latent viral infections under immunosuppressive treatment of the skin disease, is observed.
The Side Effects of Drugs Annuals from a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the 2011 publications on cytokines and monoclonal antibodies covers bone morphogenetic proteins, colony-stimulating factors, interferons alfa and beta, aldesleukin (interleukin-2) and anakinra (interleukin-1 receptor antagonist), tumor necrosis factor alfa antagonists (adalimumab, certolizumab, etanercept, golimumab, and infliximab), and a range of monoclonal antibodies (alemtuzumab, cetuximab, dacetuzumab, daclizumab, efalizumab, gemtuzumab ozogamicin, muromonab, natalizumab, omalizumab, palivizumab, panitumumab, rituximab, teplizumab, and trastuzumab). Tumor necrosis factor-alfa antagonists are being used increasingly for inflammatory conditions, such as rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel disease. Post marketing surveillance is revealing serious and potential life-threatening adverse events. The risk of infections related to TNF-alfa antagonists is discussed in detail in a special review.
