SECOND LINE THERAPY IN PSORIASIS

Dewi Sartika, Irma D. Roesyanto - Mahadi

Dermatovenereology Departement
Medical Faculty of University Sumatera Utara / H. Adam Malik General Hospital
Medan
Email : dewisartika_dr@yahoo.com

Abstract :
Background : Cyclosporine is one of the most effective systemic drugs available for
treatment of psoriasis and it is considered as second-line treatment. It is usually used
for induction of psoriasis remission. The daily dose range from 2.5 mg to 5mg/ kg with
intermittent short-term regimens. Oral cyclosporine should be divided into doses daily,
which is thought to reduce the side effect profile.

Case : A 43 years-man, with generalized plaque erythematous and scaly involving the
trunk, abdomen and extremities . The lesions are itchy and irritating. There was no
history of sore throat or other focal infections. For 8 years he used traditional medicine
but there was no good result. The initial PASI was 36.8. Then he came to the hospital
and got methotrexate, emollients and antihistamines for 4 months, but then the
methotrexate was not available and didn`t have a significant improvement. Then we
changed into cyclosporine 2x100 mg with improvement of lesions after 1 month and
there`s no side effect. The last PASI was 12,6.

Discussion : Cyclosporine is indicated for treatment of severe plaque psoriasis in

patients who are not immunocompromised. Dose and duration of cyclosporine
treatment are generally tailored to the patient`s general characteristics and specific
need. It should be adjusted throughout the treatment course in accordance with
individual efficacy and tolerability.

Keyword : Cyclosporine, psoriasis, treatment

1
Background
Psoriasis is a chronic inflammatory skin diseases residif, can be informed of all
ages are marked by red plaques covered by thick scales silvery-white and firm limits
1. The etiology of psoriasis remains unclear, although there is evidence for genetic
predisposition.2 The role of the immune system in psoriasis causation is also a major
topic of research. Although there is a suggestion that psoriasis could be an
autoimmune disease. Psoriasis can also be provoked by external and internal triggers,
including mild trauma, sunburn, infections, systemic drugs and stress3. Psoriasis
involves the skin and nails, and is associated with a number of comorbidities. Skin
lesions are localized or generalized, mostly symmetrical, sharply demarcated, red
papules and plaques, and usually covered with white or silver scales. Lesions Through
various cytokines such as TNF alpha these cells cause a chronic inflammatory state
and alter epidermal hyperproliferation, differentiation, apoptosis and neoangiogenesis
that produce the findings seen in this disease. 7

The diagnosis of psoriasis is often made upon clinical inspection of the skin.
The clinical presentation often makes diagnostic testing and pathological examination
of a biopsy from a plaque unnecessary.1,6
Systemic therapy is more commonly used in people with extensive stable
plaque psoriasis where topical therapy would be impractical and potentially unsafe
and where phototherapy is not appropriate or has failed. In one US based study, the
proportion of people with body surface area >10%.8,9
Cyclosporine is one of the most effective systemic drugs available for treatment
of psoriasis and it is considered as second-line therapy.9 The evidence of psoriasis as
an immune-mediated disease can be tracked back to 1979, when cyclosporine was
first used in kidney transplant patients to prevent graft rejection. Some of these
patients also had psoriasis, which improved after starting cyclosporine. Cyclosporine
is a cyclic polypeptide composed of 11 amino acids whose therapeutic action is
derived through the inhibition of calcineurin.4,10Cyclosporine has a broader
immunosuppressive effect that can target any immune cell regulated by calcineurin/
nuclear factor of activated T cells signaling. This was supported by a study that
showed decreased expression of genes characteristic of both Th1 and Th17 pathways
in psoriatic skin after treatment with cyclosporine. Cyclosporine has a rapid onset of
action and is one of the most efficacious systemic treatments for psoriasis.1,4,10

2
Case
A 43 years-man came with chief complaints with generalized plaque
erythematous and scaly involving the body abdomen and leg since 8 years ago. The
lesions are itchy and irritating. There was no history of sore throat or other focal
infections that might have precipitated exacerbations of these disease. For 8 years
cause itching, stinging and pain.1,2,4 Although psoriasis occur worldwide, its prevalence
varies considerably. The worldwide prevalence of psoriasis is estimated to be
approximately 2-3%.5
Psoriasis is a genetically programmed pathologic interaction between skin
cells, immunocytes and numerous biologic signaling molecules triggered by
environmental stimuli. The immune response is a cellular one; Th1 and Th17 cells are
activated by IL12 and IL23 secreted by antigen presenting cells in the skin. He used
traditional medicine but there was no good result.
Physical examinations proved that patient`s vital signs were normal. On
dermatologic examination generalized plaque erythematous and scaly involving the
trunk, abdomen and extremities (Figure 1). The initial PASI was 36,8. In laboratorium
findings, we found that 14,4 g/dL, hematocrite 42%, leukocyte 6.300/l. Liver function
SGOT 10 U/L and SGPT 18 U/L. Kidney function 1,1 mg/dL.

and emollient.
H

A B C

3
 D E F

Fig 1. Generalized plaque erythematous and scaly A) Regio abdomen and

thorakal B) Regio vertebralis C&D)Regio scalp E) Regio antebrachii F) Regio
tibialis

The patient was diagnosed with Psoriasis vulgaris and treated with initial dose
methotrexate tablet 5mg / week, antihistamine (ceterizin 10 mg) 1x1tablet and 10%
urea cream.

A B

C D

4
 Fig 2. 2 months after treatment .Generalized plaque erythematous with
moderate desquamation A) Regio abdomen and thoracal B) Regio vertebralis
C)Regio deltoid & antebrachii. Plaque erythematous with mild desquamation
on D) Regio scalp E) Regio tibialis

2 months after treatment, the patient reported that itch sensation and redness
were decreased. On dermatologic examination revealed plaque erythematous with
moderate desquamation on regio abdomen, thorakal, vertebralis, regio deltoid and
antebrachii. Plaque erythematous with mild desquamation on region tibialis and scalp
(Figure 2) and treated with methotrexate tablet 10mg / week, antihistamine (ceterizin
10 mg) 1x1tablet, folic acid 1x400g, calcipotriol- betamethasone (daivobet ointment)
and 10% urea cream. The PASI score was 28,9.

A B

C D

Fig 3. 4 months after treatment .Generalized plaque erythematous with

moderate desquamation A) Regio abdomen and thorakal B) Regio vertebralis .
Macula erythematous on C) Regio scalp. Plaque erythematous with mild
desquamation on D) Regio tibialis

4 months after treatment, the patient reported that redness were decreased.
On dermatologic examination revealed Generalized plaque erythematous with

5
moderate desquamation on regio abdomen, thoracal and vertebralis. Macula
erythematous on regio scalp. Plaque erythematous with mild desquamation on region
tibialis (Figure 3) . We changed into cyclosporine 2x100 mg because the methotrexate
was not available and didn`t have significant improvement and 10% urea cream. The
PASI score was 20,9.

A
B C

Fig 4. 1 months after changed treatment with cyclosporine. Macula erythematous

with mild desquamation A) Regio abdomen and thorakal B) Regio vertebralis C)
Regio scalp D) Regio antebrachii E) Regio tibialis

1 month after changed treatment into cyclosporine the patient reported that
redness and desquamation were decreased. On dermatologic Macula erythematous
with mild desquamation regio abdomen and thoracal, regio vertebralis, regio scalp,
region antebrachii and regio tibialis (Figure 4) . We treated with cyclosporine 2x100
mg and 10% urea cream. There`s no side effect for this patient. The PASI score was
12,6.

6
Diccusion
The diagnosis of Psoriasis based on history, clinical presentation and
laboratory findings. He had a generalized plaque erythematous on his trunk, hands
and legs. Psoriasis is a genetically programmed pathologic interaction between skin
cells, immunocytes and numerous biologic signaling molecules triggered by
environmental stimuli.1,3,6 The immune response is a cellular one: Th1 and Th17 cells
are activated by IL12 and IL23 secreted by antigen presenting cells in the skin.
Through various cytokines such as TNF-alpha these cells cause a chronic
inflammatory state and alter epidermal hyperproliferation, differentiation, apoptosis
and neoangiogenesis that produce the findings seen in this disease. 1,7
A broad spectrum of antipsoriatic treatment, both topical and systemic is
available for management of psoriasis. The most these treatments are
immunomodulatory. As psoriasis is a chronic condition, it is important to know the
safety of a treatment during long-term use. Some treatments such as calcipotriol,
methotrexate and acitretin can be regarded as appropriate for continuous use. These
treatments maintain efficacy and have low cumulative toxicity potential. 1, In this case
we gave methotrexate 5 mg/ week for initial dose and 10 mg/week for 4 months.
Methotrexate is indicated for the treatment of patients with moderate to severe
psoriasis that is unresponsive to topical therapy.7 Cyclosporine is one of the most
effective systemic drugs available for treatment of psoriasis and it is considered as
second-line therapy.1Cyclosporine is indicated for treatment of severe plaque
psoriasis in patients who are not immunocompromised.4,6 In this case, patient with
psoriasis involving more than 15%-20% body surface area (BSA) are considered to
have moderate to severe disease. He had severe plaque psoriasis with initial PASI
was 36,8. The treatment from methotrexate we changed into cyclosporine because
methotrexate was not available and didn`t have a significant improvement. After 4
months treatment of methotrexate the PASI was decreased 36,8 to 20,9. In dose and
duration of cyclosporine treatment are generally tailored to the patient`s general
characteristics and specific need. We use cyclosporine for 1 month, the PASI was
significant decreased 20,9 to 12,6. It should be adjusted throughout the treatment
course in accordance with individual efficacy and tolerability.4,8,9 In cases of itchy or
pruritic psoriasis, treatments with an irritative potential such as dithranol, vitamin D 3
analogs should be used cautiously, whereares treatments with potent anti-
inflammatory effects, such as topical corticosteroids are more appropriate.1, In this

7
case we gave antihistamine (ceterizin 10mg) 1x1 tablet and calcipotriol-
betamethasone (daivobet ointment) for itch sensation for this patient.

References :
1. Johann E., James T., Psoriasis. In : Goldsmith L., Kartz S.I., Gilchrest B.,et al.
Fitzpatrick`s Dermatology in General. 8 ED, The Mc-Graw-Hill Companies,
2012: P197-231
2. Harden J., Krueger J., The immunogenetics of Psoriasis: a comprehensive
review. Journal of Autoimmunity. 2015; 64: 66-73
3. Boehnckle W., Schon N., Psoriasis. The Lancet. Elsevier. 2015: P 1-12
4. John Y., Ethan C., in : Moderate to Severe Psoriasis. 4 th edition, CRC Taylor&
Francis Group. 2014: P 139-184
5. Monica E., Kimbal A., Psoriasis Epidemiology : The Interplay of Genes and
Environment. Journal of Investigative Dermatology. 2013: P 287-289
6. Kenneth B., Eric B., Psoriasis and Psoriasis Arthritis. Springer. 2005. P: 67-72
7. Jeffrey M., Mark L., Advances in Psoriasis. Springer. 2014.P : 9-20
8. Kamaldeep S., Inderjeet K., Efficacy and Safety of Cyclosporine versus
Methotrexate in Severe Psoriasis. The Journal of Dermatology. 2003.P : 458-
463
9. National Clinical Guideline Center. Psoriasis Assessment and Management of
Psoriasis Clinical Guideline. 2012
10. Colombo M., Cassano N., Cyclosporine regimens in plaque psoriasis: an
overview with special emphasis on dose, duration and old and new treatment
approaches. The Scientific World Journal. 2013. P: 1-11