Sulfasalazine as an Alternative Therapy for

Generalized Pustular Psoriasis:

Case Series and Review of Literature

Jhauharina Rizki Fadhilla

, Eyleny Meisyah Fitri

, Windy Keumala Budianti

, Endi Novianto

Department of Dermatology and Venereology Faculty of Medicine Universitas Indonesia/

Dr. CiptoMangunkusumo National Central General Hospital, Indonesia

Keywords: Acitretin, methotrexate, psoriasis, sulfasalazine

Abstract: Generalized pustular psoriasis (GPP), psoriasis of von Zumbusch, is infrequent and notoriously intractable

skin disease, so as the treatments remain challenging. One of the treatments of choice for GPP is acitretin

currently used by most countries. Unfortunately, our national health regulation prohibits acitretin and also

other systemic retinoids. Thus, sulfasalazine has been given to our patients due topoor responseof

cyclosporine and methotrexate (MTX) in previous treatment. We aimed to evaluate the efficacy of

sulfasalazine in GPP. Three patients affected by GPP and unresponsive to previous treatment, received

sulfasalazine started at the dosages of 1 gram/day. The dose was increased related to the response. We

observed one patient with good result after 4 months administration. The other two stopped the treatment

due to lack of response and severe digestive side effect. There were varied results of sulfasalazine therapy in

GPP. It is known to acts against molecular mechanism by inducing neutrophil apoptosis which is abundant

in GPP pathogenesis. Sulfasalazine has warranty of its availability so far, affordable, and shares efficacy as

well.

1 INTRODUCTION

Pustular psoriasis is a type of psoriasis clinically

described by small to large pustules on erythematous

skin. It is subtyped into generalized, localized

variants, and drug-induced pustular psoriasis.

Generalized pustular psoriasis consists of acute GPP,

also known as von Zumbusch type, pustular

psoriasis of pregnancy, and infantile and juvenile

pustular psoriasis. Localized pustular psoriasis

comprises palmoplantarpustular psoriasis and

acrodermatitis continua of Hallopeau. Pustular

psoriasis related drug-induced cases have been

linked with various medications.(Gudjonsson JE et

al, 2012; Sheu JS et al, 2016)

Based on histopathological analysis, pustular

psoriasis lesions express neutrophil-dominant

infiltrate. Large accumulations of neutrophils seen in

the stratum corneum and surrounded by

parakeratosis, culminate in abundant spongiform

pustules of Kogoj and microabscesses of Munro.

These histologic hints of “active” psoriasis are

discerned in pustular psoriasis.( Gudjonsson JE et al,

2012; Kerkhof PC et al,2018; Mansouri B et al

2016

)

Therapy of GPP remains challenging as its rarity

and heterogeneous nature of the disease. The clinical

practice guidelines for psoriasis are based on a

systematic review measuring skin symptoms as

progression mostly(Fujita H et al, 2018; Twelves S

et al, 2019). Fujita et al announced Japanese

guidelines for GPP at 2018. They stressed on

consideration that GPP is systemic inflammatory

response syndrome (SIRS). Consequently, primary

care, systemic maintenance, therapy of cutaneous

lesions, and complications should be highlighted.

(

Twelves S et al, 2019). Both topical and sistemic

agents are regulated as GPP treatments, the latter

including cyclosporine, MTX, acitretin, TNFα

inhibitor, other biologics,(

Fujita H et al, 2018; Twelves

S et al, 2019)

and granulocyte/monocyte adsorption

apheresis (GMA).Despite its controversy, systemic

corticosteroid is recommended in acute phase and as

second-line therapy.,(

Fujita H et al, 2018; Twelves S et

al, 2019)

According to clinical practice guidelines

released by Indonesian Society of Dermatology And

316

Fadhilla, J., Fitri, E., Budianti, W. and Novianto, E.

Sulfasalazine as an Alternative Therapy for Generalized Pustular Psoriasis: Case Series and Review of Literature.

DOI: 10.5220/0009987703160319

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 316-319

ISBN: 978-989-758-469-5



Venereology (INSDV), oral acitretin is

recommended as monotherapyfor pustular psoriasis

and erythroderma psoriasis. (Kelompok Studi

Psoriasis Indonesia Perhimpunan Dokter Spesialis

Kulit dan Kelamin Indonesia, 2014).

Sulfasalazine is extensively used in treatments of

inflammatory bowel diseasesand rheumatoid

arthritis;however it israrely as systemic agent for

treatment of GPP.(Gudjonsson JE et al,

2012;Niknahad H et al, 2017; Bertolotto M et al

2009). It is used in therapy-resistant disease or if the

previous systemic agents are not well tolerated.

Therefore, we reportthe consideration of

sulfasalazine therapy as an alternative treatment in

three cases of recalcitrant GPP.

2 CASE

2.1 Case 1

A56 years old female presented with a history of

GPP for 30 years visitedour DermatoAllergo-

Immunology clinic.She came from Wonogiri,

Central Java, and worked as a farmer. She came with

chief complaint extensive scaly erythema and

multiple pustules that form “lake of pus” on her

trunk and extremities accompanied with systemic

symptoms of fever and malaise. She had been

treated with MTX (7,5-10 mg/week), topical and

systemic steroidsin 6 months.Methotrexate was

stopped because the drug had not been available for

weeks. The medication switched to azathioprine for

a month. Regrettably, patient encountered anemia

(hemoglobin level is 10,2 gr/dL). Because of that

reason, we gave sulfasalazine with starting dose

from 1000 mg per day combined with topical

corticosteroid. After two weeks administration,

patient revealed a new erythema with sterile pustules

on her cheeks, and buttocks. We increased the

doseto 1500 mg per day. After one month, the

patient showed no more erythema and sterile pustule

arised. She had taken sulfasalazine for 4 months.

During last two months, she occasionally

experienced a small number of sterile pustules which

vanished after application of topical steroid for

several times. We also evaluated factors that could

trigger flares, include infection, smoking, and drugs.

Figure 1.Erythematous plaques with sterile pustules and

scale on left upper leg, lower left arm, left wrist, hand, and

abdomen.

Figure 2. Evaluation after four months therapy of

sulfasalazine revealed marked improvement.

2.2 Case 2

A 23-year-old female, had psoriasis vulgaris since

she was 11 years old.At the age of 13 years,she

experienced GPP with no symptoms of psoriasis

arthritis. She also had -traits thalassemia as other

comorbid. For years the disease was treated with

acitretin, MTX, varying topical and systemic steroid

with poor compliance because of economic burden.

She also had been treated with cyclosporine for 8

months and had a temporary improvement. The GPP

severity measured by body surface area, reduced up

to 1.2%. But, grievously it relapsed again and

cyclosporine did not help anymore. Then, MTX

treatment replaced cyclosporine. It was started at the

third month of oral anti-tuberculosis drug, with

approval internal medicine specialist related to her

pulmonary lung tuberculosis. She was still

experienced recurrent exacerbations of GPP for six

months. We decided to replace MTX with

sulfasalazine (1-2 gram/day) subsequently,

combined with high doses until a maintenance

dosage of oral methylprednisolone (4-20 mg/day).

The severity was moderately improved while in

addition with high dose systemic steroid. A year

after, we terminated sulfasalazine and substituted by

cyclosporine again.

Sulfasalazine as an Alternative Therapy for Generalized Pustular Psoriasis: Case Series and Review of Literature

317

2.3 Case 3

A 27-year-old female came to DermatoAllergo-

Immunology clinic presenting with multiple pustules

and extensive erythematous skin. She is a private

school teacher whose planning to get married and

and refused to take any contraception. She had GPP

for ten years and had been treated with multiple

systemic agents. According to her history,

combination of acitretin and antibiotic was very

effective opposed to MTX and cyclosporine. She

did not want to delay pregnancy after married, so we

discussed about sulfalasazine as a therapeutic choice

with the patient and family. She was agreed to be

given 1000 mg sulfasalazine per day, but after one

month, she experienced severe complaints related to

her digestive tract, such as nausea, vomiting, loss of

appetite, headache, and fatigue. On her own, she

stopped treatment and treated herself by taking

methylprednisolone 1x4 mg per day irregularly.

Three months later, patient entered our emergency

room with erythematous skin accompanied by sterile

pustules that affect almost the entire body. Lastly,

patient and her family are considering treatment with

a biologic agent. While waiting, cyclosporine,

topical and systemic steroid have been administered.

3 DISCUSSION

Acute GPP ishazardoussevere form of psoriasisthat

life threatening. The typical findings are sterile

pustules on erythematous base, and followed by

constitutional symptoms. Varied triggering factors

have been notified, including pregnancy (also named

impetigo herpetiformis), consumption and

withdrawal of corticosteroid, upper respiratory tract

infections, emotional stress, and medicines.

Systemic corticosteroid usage and withdrawal is

notable factor that cause exacerbation of GPP by

inducinginhibition of the inflammatory system.

All

of our cases have been taking systemic

corticosteroid, however we tapered the dose down

slowly and with the addition of other systemic

agents. However, it does not rule out the possibility

of using steroids that trigger flares.

To preclude the infection, we consulted our

patients to ears, nose and throat specialist, dentist,

and sexually transmitted infections division.

Infection can also cause to an acute activation of

neutrophils which may affect as a trigger for the

acute GPP. (Gudjonson et al, 2012; James WD,

2016;Fujita H et al, 2018)

Sulfasalazine acts as an anti-inflammatory

agent.(Bertolotto et al, 2009;Wright HL et al, 2010)

Sulfasalazine has long been used in treatment of

ulcerative colitis and Crohn's disease, also

rheumatoid arthritis.(Akahoshi et al, 1997; Wright

HL et al, 2010).

The drug is composed of both

sulfapyridine and 5-aminosalicylic acid (5-ASA).

Sulfasalazine has a various kinds of effects on

leukocyte functions, namely inhibition on

degranulation, chemotaxis, superoxide generation of

neutrophils,proliferation and production interleukin-

2, and also cytokine produced by

monocytes.(Niknahad et al, 2017; Bertolotto et al,

2009). These mechanism suggests that sulfasalazine

play a role in neutrophil-mediated diseases.

A case of acrodermatitis continua of Hallopeau

(ACH), as one of subtype of pustular psoriasis, was

reported successfully treated with sulfasalazine in

Department of Dermatology, the Hospital of Jiangsu

University, Zhenjiang, China. The improvement

reached after2 weeks and total remission of skin

lesions occurred after one-month therapy.(Li M et

al., 2018). The first case we reported also showed

good efficacy of sulfasalazine administration

without being accompanied by other systemic agents

for 4 months. The patient only received topical

steroids.

The side effect profile of sulfasalazine includes

headache, nausea, and vomiting, which occur in

more or less one-third of patients. Hemolytic anemia

can occur associated with glucose-6-phosphate

dehydrogenase (G6PD) deficiency. Thus, it is

important to work up baseline data of complete

blood cell count (CBC), comprehensive

metabolic panel (CMP), and G6PD. Repeat CBC

and CMP weekly for 1 month, then every 2 weeks

for 1 month, then monthly for3 months, and then

every 3 months.

In this case report, we found one of

three patients,the third caseexperienced

gastrointestinal side effects such as nausea,

vomiting, loss of appetite with headache and fatigue.

Adherence to medication appears to also play a role

in its success. The third case had a history of steroid

use that does not comply with the recommendation

of administration increases the risk of recurrent of

GPP. The other treatment that can be done is the

biologic agent.

4 CONCLUSION

The three cases demonstrate both clinical benefit and

failure that were received administration of

sulfasalazine for GPP. The mechanism of

sulfasalazineas an anti-inflammationin skin diseases

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

318



is intricate; however, its efficacy in treating these

clinically distinct cases of GPP suggests a different

underlying pathophysiological mechanism. Based on

this case series and a previous case report,

sulfasalazine can be conceived as optional treatment

choice for patients with GPP.

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