Pompholyx as a side effect of intravenous immunoglobulin (IVIg)

Abstract

Intravenous immunoglobulin (IVIg) is increasingly used across multiple specialties for the treatment of inflammatory and autoimmune diseases. Cutaneous reactions to IVIg are generally minor. Pompholyx is a common eruption of small vesicles on the palms, soles, and/or lateral aspects of the fingers. It has a multifactorial aetiology but is rarely attributed to being a drug-related side effect. We describe a 43-year-old woman presenting with peripheral sensory neuropathy who developed pompholyx eczema on both palms following treatment with IVIg.

Background

We wrote up this case to increase awareness of pompholyx eczema as a side effect of intravenous immunoglobulin (IVIg) therapy. The use of IVIg is increasing across specialties. It is important for dermatologists and physicians who use IVIg to be aware of pompholyx as a potential side effect of treatment. We also wanted to highlight that our patient had an excellent clinical response to super potent topical steroids.

Case presentation

A 43-year-old woman presented with a 2-week history of progressive peripheral sensory neuropathy. Despite extensive investigations, no cause had been identified. Full blood count, renal profile, liver profile, thyroid function tests, haematinics and immunoglobulins were all within normal limits. She had a negative viral screen, connective tissue disease screen, Antineutrophil cytoplasmic antibodies (ANCA), syphilis, anti-ganglioside antibodies, anti-myelin-associated antibodies and paraneoplastic antibodies. Her cerebrospinal fluid analysis was unremarkable. Imaging tests including a CT of the brain, an MRI of the whole spine, and CT of the thorax, abdomen and pelvis were unremarkable. She had a background history of hepatitis C. Her hepatitis C was treated successfully in 2018 with an 8-week course of Harvoni (ledipasvir/sofosbuvir). She had no complications during her hepatitis C treatment. She is under review with hepatology in our institution and is felt to have had a sustained virological response. There has never been evidence of cirrhosis at presentation or follow-up. She was also an ex-intravenous drug user. She did not take any regular prescribed or over-the-counter medication. She had not taken any medication prior to her presentation to hospital.

She was commenced on IVIg at a dose of 400 mg/kg daily for 5 days as a trial of treatment for her sensory peripheral neuropathy. After receiving her third dose of IVIg, she developed a discrete intensely pruritic vesicular rash on her palms and fingers bilaterally consistent with pompholyx (figures 1 and 2). No other areas were affected. She has no personal or family history of eczema or atopy. Apart from IVIg, she had not been commenced on any other new medications. There was no change to her diet while in hospital compared with her diet before her hospital stay.

Figure 1.

Discrete vesicular eruption on palmar surface of right hand.

Figure 2.

Discrete vesicular eruptions on palmar surface of both hands.

Differential diagnosis

This patient was reviewed and diagnosed with pompholyx given the clinical presentation specifically the time of onset, the associated itch and the fact she was systemically well. She did not undergo diagnostic biopsy as it was felt that that diagnostic biopsy would not add to her treatment. Our initial approach was to commence treatment for pompholyx and assess response. If there had been zero or little response to treatment, we would have considered biopsy at that time.

Treatment

She was started on clobetasol proprionate 0.05% ointment once daily for 2 weeks, followed by alternative days for 2 weeks. She was also advised to wash with soap substitutes and use non-fragrant emollients daily. After using this regime for 1 month, she was reviewed and her pompholyx had resolved.

Outcome and follow-up

She had an excellent clinical response to treatment. She has been seen back in dermatology clinic after 1 month and her pompholyx eczema has not returned. The patient has not undergone further treatment with IVIg as it was not felt to be necessary by her neurology team. The discontinuation of the IVIg is due to the fact that the patient had resolution of her neurological symptoms from treatment.

Discussion

IVIg contains pooled plasma from multiple donors. It is used in the treatment of multiple inflammatory and autoimmune conditions across a wide range of specialties. In addition to IgG, other immunologically active molecules such as major histocompatibility complex molecules and soluble CD4 and CD8 can be found in IVIg.¹ The differences in composition can be explained by a variety in purification methods used by manufacturers.² Rates of cutaneous adverse reactions to IVIg are reported at 0.4%–6%. These include pruritus, urticaria, alopecia, erythema multiforme, cutaneous vasculitis, morbilliform eruptions, lichenoid and eczematous reactions, most often pompholyx.^{2 3} The aetiology of IVIg-associated pompholyx is unclear.² The majority of affected patients do not have a personal history of eczema or atopy.³ There have been no reported cases in the literature of patients with immunodeficiency developing pompholyx following IVIg administration.³ This may be due to the lower dosages used in this population,^{3 4} but could also lend support to the hypothesis that antibody-mediated injury may play a part in the pathogenesis of IVIg-induced pompholyx.⁵ The development of pompholyx following IVIg treatment has been reported in both adults and children,^{2 6} and has been more frequently described in patients who have received higher doses of IVIg usually over 2 g/kg for over 3–5 days.³ In the paediatric setting, pompholyx has been reported to occur in the setting of IVIg to treat Kawasaki disease and for clinically isolated syndrome.^{6 7}

Pompholyx associated with IVIg may remain localised to the palms or soles or can progress to involve the face, trunk or limbs.² Widespread eruptions have been reported in 17% of cases.³ IVIg-induced pompholyx usually occurs 2–5 days after IVIg and can last up to 30 days.¹ IVIg-induced pompholyx has been reported to occur more frequently in men than in women.⁸ In patients who require further doses of IVIg, cutaneous reactions are likely to recur and worsen.^{3 9} Most reactions are successfully managed with topical steroids.⁸ Recalcitrant cases have been managed with oral steroids to varying success.⁸ It has been suggested that changing the IVIg preparation may reduce the recurrence of cutaneous reactions in the group of patients who require further treatment with IVIg.⁸ It is important for dermatologists to be aware and recognise the cutaneous side effects of IVIg given its increasing use. It is also important for all specialists who use IVIg in the treatment of patients to be aware and recognise pompholyx as a side effect of IVIg.

Patient’s perspective.

I found the experience of being admitted to hospital with numbness in my legs to be scary. The rash that developed during my treatment was itchy and uncomfortable. I was reassured when the dermatology team reviewed me and gave me a treatment plan. I hope by sharing my case, it will highlight this rash if it was to occur for other patients.

Learning points.

• It is important for dermatologists to be aware and recognise the cutaneous side effects of intravenous immunoglobulin (IVIg) given its increasing use.

• It is important for all specialists who use IVIg in the treatment of patients to be aware and recognise pompholyx as a side effect of IVIg.

• The pathogenesis of IVIg-induced pompholyx is not fully understood. An antibody-mediated reaction may play a role.

• Cutaneous reactions to IVIg are likely to recur and worsen if subsequent doses are given.

Ethics statements

Patient consent for publication

Obtained.