Delayed eczematous skin reaction as an adverse drug reaction to immunoglobulin infusions: A case series

Annales de Dermatologie et de Vénéréologie

Available online 24 June 2022

In Press, Corrected ProofWhat are Corrected Proof articles?

Original article

Delayed eczematous skin reaction as an adverse drug reaction to immunoglobulin infusions: A case series

Author links open overlay panelC.BarthelaC.Berniera

https://doi.org/10.1016/j.annder.2022.05.002Get rights and content

Abstract

Background

Pompholyx and eczematous reactions are known adverse reactions to intravenous immunoglobulins (IVIg) infusion, but little is known about their clinical characteristics, associated outcomes and management.

Objective

To describe IVIg-induced eczematous skin reactions.

Methods

We conducted a retrospective study on cases of delayed skin reactions post-IVIg infusion notified to the French Regional Pharmacovigilance Centre from 1985 to 2020.

Results

A total of 27 patients were identified, of whom 85% were male. IVIg infusions were given in a neurological indication in 82% of cases. Eczematous skin reactionsoccurred in two-thirds of cases after the first infusion, with a median time to onset of 11 days. Palmoplantar pompholyx was the most common presentation, being seen in 63% of patients. Other eruptions were erythemato-squamous or maculopapular. Eight patients were classified as severely affected and developed extensive lesions (> 50% BSA). One third of the 27 patients required hospitalization. All of the severe eczematous reactions involved males receiving high doses of IVIg for neurological diseases. Biopsies of severe cases revealed a common non-specific eczematous pattern. Relapses were frequent and more severe than the initial reaction. Reintroduction of the same IVIg product consistently resulted in relapse, whereas switching IVIg type produced relapse in only 53% of patients.

Conclusion

We present the largest retrospective study of delayed skin reactions after IVIg infusions. This side-effect may be severe and have a polymorphic presentation. Relapse occurs frequently but less consistently after IVIg switch.

Introduction

Intravenous immunoglobulins (IVIg) are widely used in replacement therapy in primary and secondary immune deficiencies and for curative purposes in autoimmune and alloimmune diseases [1]. IVIg effects are based on various mechanisms, among which the modulation of complement activity, destruction of pathogenic autoantibodies, and diminution of pro-inflammatory cytokine production [2]. IVIg are well tolerated, and the reactions that occur during infusion are mostly benign. These reactions, which include fever, chills, nausea, headache and myalgia, are defined as flu-like symptoms. Serious adverse effects are rare and occur in fewer than 1% of patients; anaphylactic shock, thrombosis, aseptic meningitis, haemolytic anaemia, and kidney failure have been described [3]. Apart from urticaria, which has an estimated incidence of around 6%, other adverse dermatological effect have seldom been reported [4]. In the literature we found sporadic case reports of baboon syndrome, alopecia, lichenoid drug eruption and erythema multiforme [5], [6], [7], [8], [9]. Among delayed cutaneous side-effects, pompholyx is the most common. To date, two literature reviews are available based on case reports and one retrospective study of 9 patients regarding pompholyx and delayed eczematous reactions [10], [11], [12]. These three studies report the occurrence of eczematous reactions and pompholyx in 78%, 86%, and 95% of cases in patients treated for neurological disease [10], [11], [12]. More than 79% of patients presenting this adverse effect were men. A literature review by Gerstenblith et al. identified 64 patients with pompholyx and eczematous reactions following IVIg infusion [11]. The authors noted the occurrence of eczematous reactions in 75% of cases up to 8 days after the first IVIg infusion. Moreover, it was reported that recurrence of eczematous reaction with subsequent IVIg infusions was almost universal, with 80% to 100% of patients being affected [10], [11], [12]. However, the lack of follow-up and the small number of patients presenting reactions prevented us from evaluating the risk of recurrence. Little is known about these severe eczematous reactions, and only three patients having a widespread generalized form are described in the largest review of the phenomenon [11]. In our clinical experience, where chronic or widespread, such eczematous reactions generally impact quality of life and may lead to early treatment discontinuation. We therefore conducted a retrospective case series in order to better describe delayed eczematous skin reactions to IVIg, their initial clinical presentation, and the outcome in the classical and severe forms.

Section snippets

Patients

We conducted a retrospective observational and descriptive study of adverse cutaneous effects related to IVIg infusion, based on the regional pharmacovigilance database. Data extraction was performed by the National pharmacovigilance databank service at the Agence Nationale de Sécurité du Médicament (ANSM), using the ATC (Anatomic, Therapeutic and Chemical) classification code JO6B and the SOC (System Organ Class) code, respectively, for the classification of IVIg and cutaneous side effects.

Clinical characteristics

A flow chart of the study is given in Fig. S1 (supplementary material available online). Table 1 describes the characteristics of our population and the initial eczematous reaction. Most patients were male (85%), with a median age of 67.5 years at the time of the eruption. Patients were treated for neurological disease in 82% of cases. The eruption followed the first course of IVIg in 18 patients (69%). The median time to onset of eruption was 11 days (7–17) post infusion. The eruption was

Discussion

IVIg prescriptions for the purpose of immunomodulation have increased in recent decades as validated indications become more numerous [1]. As the number of prescriptions increases, more adverse effects are observed. We conducted the largest retrospective study on delayed eczematous reactions related to IVIg infusion. This adverse effect, whilst rare, can lead to impaired quality of life and early treatment discontinuation.

Our findings are consistent with previous studies, with eczematous

Funding sources

None.

Disclosure of interests

The authors declare that they have no competing interest.

References (20)

• F. Cohen-Aubart et al.

  Intravenous immunoglobulins-induced eczematous eruption: a long-term follow-up study

  Eur J Intern Med

  (2009)
• M.R. Gerstenblith et al.

  Pompholyx and eczematous reactions associated with intravenous immunoglobulin therapy

  J Am Acad Dermatol

  (2012)
• S.M. Dietrich Yockey et al.

  Intravenous immunoglobulin-induced lichenoid dermatitis: a unique adverse reaction

  Mayo Clin Proc

  (1997)
• D. Chan-Lam et al.

  Alopecia after immunoglobulin infusion

  Lancet

  (1987)
• P. Cherin et al.

  Management of adverse events in the treatment of patients with immunoglobulin therapy: A review of evidence

  Autoimmun Rev

  (2016)
• D. Adams et al.

  Hiérarchisation des indications des immunoglobulines humaines polyvalentes en situation de forte tension d'approvisionnement

  (2019)
• P. Guilpain et al.

  Immunomodulatory effects of intravenous immunoglobulins

  Presse Med

  (1983 2004)
• T.H. Brannagan et al.

  Complications of intravenous immune globulin treatment in neurologic disease

  Neurology

  (1996)
• A. Barbaud et al.

  A Baboon syndrome induced by intravenous human immunoglobulins: Report of a case and immunological analysis

  Dermatology

  (1999)
• K.J. Smith et al.

  Lichenoid/interface cutaneous eruptions to ivigs with the primary infusion may be related to the re-regulation of anti-idiotype network

  J Cutan Med Surg

  (1998)

There are more references available in the full text version of this article.

Sent from my iPhone

Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

Please excuse the shortness of this message, as it has been sent from
a mobile device.