A review of disease burden and clinical management for generalized pustular psoriasis in China

Figures & data

Table 1. Genetic risk factors in Chinese patients with GPP.

Gene	Mutation	Outcome
IL-36RN	Biallelic mutations	Disease onset is earlier than patients with heterozygous or without IL-36RN mutation (26.83 years vs. 33.27 and 38.03 years)
	All IL-36RN mutations	70.59% patients with GPP alone, 37.78% patients with GPP with PV (OR = 3.95; P = .02)
	Mutation in p.Arg10ArgX1^a	70.59% patients with GPP alone, 26.67% patients with GPP with PV (OR = 6.60; P = 2.0x10^−3)
CARD14	Mutation in p.Asp176His	The frequency of the mutation was 5.6-fold higher in patients with GPP than those without GPP
	Mutation in p.Arg820Trp	Strong association with GPP
AP1S3	-	-

^aThe most frequently reported IL-36RN variant in Chinese population; -, not identified

PV, psoriasis vulgaris; OR, odds ratio.

Figure 1. IL-36 signaling pathway in normal skin and in skin with GPP.

In normal skin, expression levels of interleukin (IL)-36 (α, β, γ) and IL-36RA are in balance, and the binding of IL-36RA to IL-36R suppresses the IL-36 signaling pathway. In generalized pustular psoriasis (GPP), overexpression of IL-36 (A) or mutated IL-36RA (B) that cannot bind to IL-36R activates IL-36 signaling, which leads to overproduction of proinflammatory cytokines and chemokines, subsequently resulting in immune cell recruitment (neutrophils, monocytes and dendritic cells), as well as keratinocyte proliferation and pustule formation. The cascade of these events contributes to the development of GPP and its clinical presentation [23–25].

Table 2. Summary of therapies recommended by global guidelines for management and treatment for GPP and clinical experience in China for GPP, based on disease condition^a.

Disease condition	Retinoids	Immunosuppressant	Biologic agents	Corticosteroids	Other
Acute GPP (during acute period)	Acitretin^b	Methotrexate,^b cyclosporine^b	TNF-α inhibitors^b (e.g. etanercept, infliximab and adalimumab); IL-12/23 inhibitors (e.g. ustekinumab); IL-23 inhibitors (e.g. guselkumab and risankizumab); IL-17 inhibitors (e.g. secukinumab, ixekizumab and brodalumab)	-	Dust powder,^c lotion,^c bland emollient^c
Acute GPP (during chronic period)	-	-	-	-	NB-UVB,^c PUVA,^c starch bath,^c warm-water bath^c
Complications of acute GPP
Fever; fluid and electrolyte disorder; hypocalcemia; sepsis	-	-	-	-	Rest, close monitoring of vital signs, basic supportive care
Cardiovascular and respiratory system	-	-	-	Glucocorticoids (when infection is excluded)	-
Joint	-	Methotrexate, sulphasalazine, cyclosporine	TNF-α inhibitors	-	-
Annular GPP	-	-	-	-	Topical therapy with mild or moderate glucocorticoids; combination therapy of systemic and physical therapy (if conditions worsen or outcome is inadequate)
GPP in pregnancy	-	Cyclosporine^b,d	TNF-α inhibitors^b (e.g. certolizumab can be considered for the entire pregnancy period)	Glucocorticoids^b,d	IVIG^f, plasma infusion^f, bland emollient,^c NB-UVB,^c PUVA^c
Juvenile and infantile GPP	Acitretin^b,d	Cyclosporine,^b,e methotrexate^b	TNF-α inhibitors^b (e.g. etanercept for children aged ≥6 years; infliximab and adalimumab for children aged ≥4 years); IL-12/23 inhibitors (e.g. ustekinumab for children aged ≥12 years)	-	IVIG (can be considered for infants),^b,f bland emollient,^c NB-UVB^c (during chronic period)
Localized GPP	-	-	-	-	topical therapy with mild or moderate glucocorticoids; combination therapy of systemic and physical therapy (if conditions worsen or outcome is inadequate)

^aThe therapies listed in the table are derived from the American guidelines of treatment for pustular psoriasis; Japanese guidelines of management and treatment for GPP; and the guidelines of diagnosis and treatment for psoriasis in China (2018 complete edition) [28,35,42].

^bMedications that are considered as first-line therapy. ^cMedications that are considered as second-line therapy.

^dMedications that should be considered with caution. ^eCyclosporine is preferred in children aged >1 year, and superior to acitretin and methotrexate.

^fMedications that are recommended for patients who are not suitable for biologic agents due to certain conditions such as contraindications.

GPP, generalized pustular psoriasis; IL, interleukin; IVIG, intravenous immunoglobulin;; NB-UVB, narrow-band ultraviolet B; PUVA, psoralen and ultraviolet A; TNF, tumor necrosis factor.

Table 3. Summary of therapies for adult patients with GPP in China, based on therapy category^a.

Therapy category	Retinoids	Immunosuppressants	Biologic agents	Traditional Chinese Medicine (TCM)	Other
Systemic therapy	Acitretin^b,c	Cyclosporine A,^b methotrexate,^b,c mycophenolate mofetil	Infliximab^b	Tripterygium wilfordii and related agents	Dapsone, hydroxyurea
Topical therapy	-	-	-	-	Calamine, bland emollient
Physical therapy	-	-	-	TCM bath	NB-UVB, PUVA

^aThe therapies listed in the table are recommended by the guidelines of diagnosis and treatment for psoriasis in China (2018 complete edition) [28].

^bMedications that are considered as first-line therapy.

^cMedications that are contraindicated due to teratogenic effects on the fetus. Acitretin: women who are of childbearing age should use contraception while receiving acitretin until ≥3 years after discontinuation of acitretin; it is contraindicated for pregnant women. Methotrexate: women should use contraception for 3 months after discontinuation of methotrexate; it is contraindicated for pregnant and lactating women.

GPP, generalized pustular psoriasis; NB-UVB, narrow-band ultraviolet B; PUVA, psoralen and ultraviolet A.

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