Mariko Seishima 1 2, Kento Fujii 3, Yoko Mizutani 3 Am J Clin Dermatol 2022 Jun 15. doi: 10.1007/s40257-022-00698-9.
Generalized Pustular Psoriasis in Pregnancy: Current and Future Treatments
Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disease characterized by sudden widespread eruption of sterile pustules with or without systemic symptoms. GPP may be life threatening in cases with severe complications such as cardiovascular failure, acute respiratory distress syndrome, and serious infections. Impetigo herpetiformis (IH) is a GPP that is induced and exacerbated by pregnancy and occurs most frequently during the last trimester. IH may result in poor or fatal neonatal outcomes, including placental insufficiency, fetal abnormalities, stillbirth, and early neonatal death. Most patients have prompt remission in the postpartum period; however, earlier appearance and more severe symptoms are observed during subsequent pregnancies. Appropriate treatment and close monitoring of the mother and fetus are vital for the management of patients with IH. Particular attention is required for the management of patients with IH to avoid an influence on the fetus. However, data regarding treatments for GPP in pregnant women are sparse. Over the last decade, many patients with IH have been treated with cyclosporine, corticosteroids, tumor necrosis factor-α inhibitors, interleukin (IL)-17 and IL-12/23 inhibitors, and granulocyte and monocyte adsorption apheresis (GMA). GMA may be an important option for patients with IH as it is presently one of the safest available therapeutic options, but there have been no reports to fully confirm its safety in pregnant patients with GPP. Alternatively, based on recent advances in the understanding of the role of the IL-36 axis in the pathogenesis of GPP, biologic agents that target the IL-36 pathway may demonstrate promising efficacy in IH.
EO5-01 A case of pustular psoriasis deteriorated during the second pregnancy was successfully treated with intensive GMA and certolizumab pegol
Asumi Fujii, Yuki Hattori, Miho Kawamura, Yoko Mizutani, En Shu, Mariko Seishima
poster at ISFA 2019 pag 141-142
A 31-year-old woman with the IL36RN gene mutation developed psoriasis at 3 years old. As she had pustular psoriasis at 16 years old, she was treated with cyclosporine (Cys), resulting in remission at 20 years old. Afterwards, she had been maintained by topical treatment for long years.During the first pregnancy at the age of 29, she developed pustular psoriasis at 29 weeks
of gestation. She received one course of granulocyte / monocyte adsorption apheresis (GMA) with Cys and prednisolone (PSL), and gave birth to a girl at 33 weeks of gestation. The baby was a low birth weight child, but is healthy and has no problems in growth and development until now. However, the patient did not sufficiently improve symptoms after delivery. We thus started the treatment with infliximab (IFX) BS at 2 months postpartum. During the second pregnancy at the age of 30, we continued the IFX-BS administration. She had erythema and pustules rapidly enlarged from 23 weeks of pregnancy. Oral administration of PSL and GMA were started. However, we switched the therapy to intensive GMA (twice in a week), because the effect was insufficient. Initially, administration of IFX-BS was scheduled to end at 30 weeks of gestation, but due to unstable symptoms, we considered it was necessary to use another biologics even after 30 weeks of gestation. We switched to non-placental certolizumab pegol (CTZ) from 26 weeks of gestation and continued the administration until delivery, and she gave birth to a girl at 35 weeks of gestation. Although the baby was a low birth weight child, there was no physical abnormality and the baby was discharged after gaining weight. After delivery, administration of CTZ was discontinued and the PSL dose was gradually reduced. However,reintroduction of biologics is under consideration, because erythema and pustules still remain.
Efficacy and Safety of Adsorptive Granulocyte and Monocyte Apheresis in Elderly and Pregnant Patients With Ulcerative Colitis
Kazuki Yanagisawa 1, Minoru Murakami 2, Yuya Kondo 1, Shun Oguma 1, Shun Kobayashi 1, Hiroshi Miyasaka 1, Tomoaki Shinohara 3, Akihisa Tomori 3, Yui Nakano 2, Shunichi Furuhata 2, Masaya Ikezoe 2 , Ther Apher Dial 2019 Jun;23(3):217-223.
In patients with active ulcerative colitis (UC), adsorptive granulocyte/monocyte apheresis (GMA) is expected to promote remission. We conducted a retrospective cohort study to evaluate the efficacy and safety of GMA in patients with active UC. Twenty‐one UC patients including five pregnant or lactating mothers and four elderly patients (aged >60 years) received up to 10 GMA sessions. UC severity was evaluated at baseline and after GMA therapy according to Lichtiger’s Clinical Activity Index (CAI). We defined clinical remission as CAI ≤4. Overall, the median CAI score after GMA therapy had decreased from 9 to 4 (P < 0.001). The clinical remission rate was 62%, but in the elderly and pregnant or lactating mothers, the remission rates were 100% and 60%, respectively. No severe adverse effects were seen in this study. Our results may support GMA as an effective and safe treatment for active UC patients, including elderly patients and pregnant cases.
Successful remission of ulcerative colitis flare-up during pregnancy with adsorptive granulomonocytapheresis plus tacrolimus
Tomoyoshi Shibuya 1, Keiichi Haga 1, Masato Kamei 1, Koki Okahara 1, Shoko Ito 1, Masahito Takahashi 1, Osamu Nomura 1, Takashi Murakami 1, Masae Makino 1, Tomohiro Kodani 1, Dai Ishikawa 1, Naoto Sakamoto 1, Taro Osada 1, Tatsuo Ogihara 1, Sumio Watanabe 1, Akihito Nagahara 1 , Intest Res. 2018 Jul;16(3):484-488.
Our experience indicates that GMA, as a non-drug therapeutic intervention with a favorable safety profile, plus tacrolimus might be a relevant treatment option for patients with active IBD during pregnancy. A future study of a large cohort of pregnant patients should strengthen our findings.
Changes in Treatment with Granulocyte and Monocyte Adsorptive Apheresis from the Past to Future in Patients with Inflammatory Bowel Disease
Shingo Kato, Akira Ishibashi, Kaori Sugiura, Kazuhito Kani, Tomonari Ogawa, Hajime Hasegawa, Koji Yakabi, Contrib Nephrol 2018;196:200-208.
GMA decreases inflammatory cytokines and upregulates regulatory T cells. Intensive GMA is significantly more effective than weekly GMA in patients with IBD. The frequency of GMA sessions per week positively correlates with treatment effects. GMA can be safely used in pregnant women and children because of its low adverse event rates. Maintenance therapy and rescue therapy for loss of response of anti-tumor necrosis factor (TNF)-α antibodies are effective. Optimal patients who responded to combination therapy with infliximab and GMA showed aggravation characteristics against infliximab treatment at week 4. Key Message: Prospective randomized blinded studies using a sham column should be performed for the loss of response against anti-TNF-α antibodies.
Therapeutic Apheresis in Pregnancy: Three Differential Indications With Positive Maternal and Fetal Outcome
Giuseppina Perrone 1, Roberto Brunelli 1, Eleonora Marcoccia 1, Ilaria Zannini 1, Miriam Candelieri 1, Maria Gozzer 2, Claudia Stefanutti 3
When approaching TA in pregnancy, clinicians have to consider the severity of disease, the strength of the indications, and the gestational age. Each case must be evaluated individually on the basis of existing evidence since, despite the increasing use, specific guidelines for apheresis in pregnancy are still lacking.
Ulcerative colitis and granulocyte-monocyte-apheresis: Safety and efficacy of maintenance therapy during pregnancy.
Valeria D’Ovidio 1, Donatella Meo, Maria Gozer, Marco E Bazuro, Piero Vernia, J Clin Apher. 2015 Feb;30(1):55-7.
To minimize symptoms and the risk of severe clinical relapse, a maintenance GMA treatment was performed throughout pregnancy. The course of pregnancy was uneventful with no side effects; the mother and the baby were all healthy and well at the delivery.
Flare up of ulcerative colitis during pregnancy treated by adsorptive granulocyte and monocyte apheresis: therapeutic outcomes in three pregnant patients.
Hiroki Takahashi 1, Kaori Sugawara, Mikako Sugimura, Masahiro Iwabuchi, Yutaka Mano, Katsuaki Ukai, Keiichi Tadokoro, Arch Gynecol Obstet. 2013 Aug;288(2):341-7.
In these three cases with active ulcerative colitis during pregnancy, granulocytapheresis as a non-pharmacologic treatment was effective and safe. In case 3 that did not respond well to the initial granulocytapheresis sessions, a moderate dose of prednisolone enhanced the efficacy of granulocytapheresis and tapering of prednisolone shortly after administration was not associated with relapse.
Granulocyte and monocyte adsorption apheresis for Behçet’s disease in a pregnant woman.
Yuko Higashi 1, Mitsuyoshi Shimokawa, Kazuhiro Kawai, Takuro Kanekura, J Dermatol. 2013 Dec;40(12):1042-4.
We present a 39-year-old pregnant woman with Behçet’s disease who was treated successfully with granulocyte and monocyte adsorption apheresis (GMA). There were no complications or adverse effects during her pregnancy and delivery. The neonate manifested no abnormalities.
Therapeutic efficacy of leukocytapheresis in a pregnant woman with severe active ulcerative colitis
H Okada 1, C Makidono, R Takenaka, S Hiraoka, A Fujiwara, J Kato, Y Kawahara, H Kawamoto, M Mizuno, Y Shiratori
Leukocytapheresis has recently been used to induce remission in patients with ulcerative colitis (UC) who fail to respond to corticosteroids. We could not find a report in the literature on leukocytapheresis for UC with gestational exacerbation. We have recently encountered this unique condition and report the details here. A 30-year-old Japanese woman with left-sided severe UC was corticosteroid-dependent and had recurrence of the active disease during tapering of corticosteroid. She declined any dose increase and the use of any immunosuppressive agent because she was in the 13th week of pregnancy. Then, concomitant leukocytapheresis was performed without increasing the corticosteroid dose. Recovery was rapid and dramatic. Mucous and bloody stool decreased after the first session, and she had remission 2 weeks later. She underwent a total of four sessions without complications. After 6 weeks, she was discharged from our hospital and underwent maintenance treatment as an outpatient with mesalazine and corticosteroid tapering. Subsequently, she gave birth to a healthy baby girl by an uncomplicated vaginal delivery while keeping the remitted stage of UC.
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