Excellent Response to Secukinumab in Treatment Resistant Impetigo Herpetiformis

Dear Editor,

Impetigo herpetiformis (IH) is a rare variant of generalized pustular psoriasis (GPP) occurring mostly in the last trimester of pregnancy and has a rapid resolution in the postpartum period. The patient presents with multiple pustules that later coalesce together and spread covering a large area. Though maternal mortality is rare, there are increased risk of adverse fetal outcomes such as intrauterine growth retardation, premature rupture of membrane, low birth weight, and even stillbirth. There is a possibility of recurrence in the subsequent pregnancies.[1] We report a case of a lady with IH who did not respond to conventional treatment and had an excellent response to secukinumab.

A 34-year-old second gravida, presented with multiple pustules over the abdomen at 26 weeks period of gestation. These lesions gradually increased to involve trunk and extremities over one week. It was associated with fever, skin discomfort, cold intolerance, and swelling of both the upper and lower limbs. She denied a history of prior skin disease. She had tachycardia (pulse – 116 per min), tachypnoea (respiratory rate – 24 per min), and pedal oedema. Dermatological examination revealed generalized involvement of trunk, abdomen and extremities in the form of multiple pustules over an erythematous base and erythematous plaques studded with pustules. Scalp showed scaling while nails, palms, soles, joints, and oral mucosa were within normal limits [Figure 1]. Laboratory investigations showed a total leukocyte count of 18300/mm3 and raised C-reactive protein. Rest of the investigations including liver, renal function, thyroid function, and serum calcium were within normal limits. Histopathology of skin showed parakeratosis, Munro’s microabscesses and spongiform pustules of Kogoj. Ultrasound abdomen showed no intrauterine growth restriction. The patient was diagnosed as IH and was started on prednisolone @1 mg/kg for two weeks with partial improvement. Cyclosporine@5 mg/kg was added and prednisolone was tapered slowly due to sub-optimal response. Even after two weeks, the response was suboptimal and we decided to start secukinumab after discussing risks and benefits. Secukinumab was administered in the dose of 300 mg subcutaneous at 0, 1, 2, 3, 4 weeks and monthly thereafter. The patient had complete resolution of her lesions four weeks after starting secukinumab [Figure 2]. The 5-points physician global assessment severity score reduced to 0 (clear) from 4 (severe) after four weeks of treatment. She delivered a full-term, healthy male child weighing 2.8 kg by elective cesarean section at 37 weeks. She was advised to continue breastfeeding and avoid live vaccinations for the neonate.

Figure 1.

Erythematous plaques, discrete, and coalescing pustules over abdomen

Figure 2.

Complete skin clearance four weeks after starting Secukinumab 300 mg subcutaneous weekly

IH is a rare disease that occurs during pregnancy and can be potentially fatal to the mother as well as the foetus. The exact etiology of this disease remains unclear. The compound heterozygous or homozygous mutation of interleukin 36 receptor antagonist (IL36RN) leading to the unrestrained activity of IL-36 plays a major role. Biologics that target IL36 such as spesolimab have shown promising results in the management of GPP.[2] TNF a, IL-1, and IL-17 stimulate IL-36, and inhibition of these cytokines can disrupt IL-36 mediated inflammation in patients with GPP.[3] Drugs, infections, hypocalcaemia, hypoparathyroidism, and pregnancy may trigger GPP in genetically predisposed individuals. The treatment guidelines for IH remain unclear due to the rarity of the disease and teratogenic effects of the available drugs. The risk-benefit ratio needs to be taken into account before starting treatment in this setup and hence much of the treatment data is anecdotal. Prednisolone is considered the drug of choice followed by cyclosporine in unresponsive patients. Tumor necrosis factor-a (TNF-a) inhibitors especially infliximab is considered biologic of choice for its management. Adalimumab has also been used effectively. Etanercept though considered safe till 28-32 weeks of pregnancy owing to its short half-life, has slower onset of action and is not suitable for treatment of GPP. These biologics can potentially be transmitted to the fetus and live vaccination has to be avoided for six months after birth. The avoidance of live vaccination like BCG in neonate predispose them to severe form of tuberculosis like tubercular meningitis, and is potentially harmful in a tuberculosis endemic country like India. None of the available biologics are approved for use in pregnancy. Certolizumab pegolis, a newer pegylated Fc-free, anti-TNF a monoclonal antibody does not undergo FcRn mediated transfer across the placenta and is considered safe for use in pregnant women.[4]

Secukinumab is a fully human, IgG1 monoclonal antibody against IL-17 and is approved for the management of psoriasis and psoriatic arthritis. It was found to be effective in 12 Japanese patients with GPP in an open-label multicentric study.[5] Secukinumab was found to be effective in a Japanese patient not responsive to granulocyte-monocyte apheresis and cyclosporine@5 mg/Kg. Chhabra et al.[6] reported a case of 26-year-old female with IH who responded to Secukinumab after showing poor response to prednisolone and cyclosporine. In our case, the patient showed excellent response to Secukinumab and showed favourable maternal and fetal outcome. Secukinumab appears to be a good choice in the management of this rare disease especially in patients not responding to first-line treatment.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.