Download - Dermatologica Sinica

DERMATOLOGICA SINICA 30 (2012) 108e111
Contents lists available at SciVerse ScienceDirect
Dermatologica Sinica
journal homepage: http://www.derm-sinica.com
CASE REPORT
New-onset guttate psoriasis following intravesical immunotherapy of Bacillus
CalmetteeGuerin
Chih-Tsung Hung 1, Wei-Ming Wang 1, Chih-Wei Tsao 2, Chien-Ping Chiang 1, *
1
2
Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Department of Urology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received: Feb 7, 2012
Revised: Mar 2, 2012
Accepted: Mar 2, 2012
Intravesical Bacillus CalmetteeGuerin (BCG) is usually a well-tolerated treatment for urethelial carcinoma of the bladder. A 60-year-old male endured multiple erythematous white-scaled maculopapules
over his trunk, back, and four extremities after 2 months of the 6-weekly intravesical instillation of BCG.
Skin biopsy revealed parakeratotic hyperkeratosis, intracorneal neutrophilic Munro’s abscess, and
acanthosis. Guttate psoriasis was diagnosed, and he was treated successfully with topical steroid and
narrow band UV-B phototherapy. We present the first Asian case of guttate psoriasis associated with
intravesical BCG immunotherapy and review the literatures.
Copyright Ó 2012, Taiwanese Dermatological Association.
Published by Elsevier Taiwan LLC. All rights reserved.
Keywords:
Bacillus CalmetteeGuerin
guttate
psoriasis
urothelial carcinoma of bladder
Introduction
Several cutaneous complications have been reported with the use
of intravesical Bacillus CalmetteeGuerin (BCG) immunotherapy,
the mainstay treatment for superficial bladder cancer. These
complications have included granulomatous lesions of the penis,
painful ulcers and papules, and inguinal lymphadenopathy. Here,
we describe a case with new-onset guttate psoriasis after the
completion of one course of intravesical BCG immunotherapy.
Case report
After diagnosis with high-grade urothelial carcinoma of the
bladder, clinical stage T1N0M0, a 60-year-old male underwent
intravesical BCG immunotherapy in the form of 6-weekly intravesical instillations of BCG. Two months after the sixth BCG instillation, multiple skin lesions appeared on the patient’s trunk, back,
and four extremities. The patient had no history of psoriasis or
other systemic diseases, and no signs of acute upper respiratory
tract infection had been noted before the onset of the skin lesions.
Furthermore, no family history of psoriasis was traced.
Physical examination revealed numerous scattered asymptomatic erythematous white-scaled papules and plaques involving the
trunk, back, and four extremities as well as Auspitz’s sign, but no
pitted nails or dermatological complications of the scalp, face, or
palmoplantar regions (Figure 1A). The results of tissue biopsy from
the medial aspect of the right forearm revealed the presence of
parakeratotic hyperkeratosis, acanthosis (Figure 2A), and intracorneal neutrophilic Munro’s abscess (Figure 2B). Observation of
immunohistochemical staining with activated phospho-Stat-3
(Tyr705; 1:1000) and psoriasin (S100A7; 1:750) revealed the
concentration of the former in the nuclei of the keratinocytes
(Figure 3A) and of the latter in the epidermis of the lesions
(Figure 3B). Based on these clinical and pathological findings, the
patient was diagnosed with guttate psoriasis.
The patient was treated with 18 applications of systemic
narrow-band UV-B phototherapy (300e1200 mJ) and twice-daily
application of 0.1% diflucortolone valerate cream on the lesions.
This treatment, which relieved his symptoms, resulted in the
development of Woronoff’s rings in the normal skin adjacent to the
psoriatic macules (Figure 1B). Three weeks after beginning
dermatological therapy, the patient resumed BCG instillation
immunotherapy to treat his bladder cancer. As anticipated, the
extent of his guttate psoriasis worsened with the resumption of
BCG instillation immunotherapy.
Discussion
* Corresponding author. Chien-Ping Chiang, M.D., Ph.D., No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City 114, Taiwan, ROC. Tel.: þ886 2 87927180;
fax: þ886 2 87927181.
E-mail address: [email protected] (C.-P. Chiang).
Vaccination with BCG, a live attenuated Mycobacterium bovis vaccine
used to stimulate the immune system and prevent severe forms
of infection caused by mycobacterium tuberculosis, is practiced
on a national scale in Taiwan. However, several dermatological
1027-8117/$ e see front matter Copyright Ó 2012, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC. All rights reserved.
doi:10.1016/j.dsi.2012.03.001
C.-T. Hung et al. / Dermatologica Sinica 30 (2012) 108e111
109
Figure 1 (A) Multiple erythematous white-scaled maculopapules involving the trunk, back, and four extremities. (B) After narrow band UV-B and topical steroid treatment,
Woronoff’s rings developed in the normal skin adjacent to psoriatic macules.
Figure 2 Histiological features of the lesion. (A) The macule located on the medial side of forearm reveals hyperkeratotic acanthosis with a dermal cellular infiltration [hematoxylin
and eosin (H&E), 40]. (B) There are multiple intracorneal neutrophilic Munro’s abscess (H&E, 400).
complications have been reported with BCG vaccination, with the
severity of the complications depending on the immunity of the
host. Skin complications that have been reported in immunocompetent hosts include juvenile sarcoidosis over the dorsum of
the hands and feet,1 keloid and delayed tuberculoid granuloma
formation on the BCG vaccination site,2 and granulomatous
inflammation of vaccination site in patients with Kawasaki’s
disease.3 In 1955, Raaschou-Nielsen4 reported the first case of
psoriasis following BCG vaccination that appears in the literature.
In 2004, Koca et al5 reported the successful treatment of a case in
the form of guttate psoriasis-like lesions on a 7-year-old boy 1
week after BCG vaccination with 3 weeks of topical corticosteroid
therapy.
In addition to serving a means of vaccination, intravesical BCG
immunotherapy is regarded as a standard and well-tolerated
means of treating superficial bladder cancer. The mechanism
underlying the therapeutic effect of BCG instillation is induction of
inflammation and stimulation of helper and killer T lymphocytes,
Figure 3 Immunohistochemical staining showing (A) Phospho-Stat-3 [1:1000; Phospho-Stat-3 (Tyr705) antibody; Cell Signaling Technology Inc., Beverly, MA, USA] is expressed in
the nuclei of the keratiocytes (400). (B) Psoraisin (S100A7; 1:750; Abcam, Cambridge, MA, USA) is expressed in the whole layer of the epidermis (400).
110
C.-T. Hung et al. / Dermatologica Sinica 30 (2012) 108e111
Table 1 Clinical features of cases with psoriasis associated with intravesical Bacillus CalmetteeGuerin (BCG) published in the literature.
No.
Sex/age
and race
Location/morphology
Bladder cancer
(grading)
Past history
of psoriasis
Additional findings
Treatment
Reference
1
M/52
NA
Plaques of psoriasis on the
elbows
Grade III
Yes
NSAIDs and steroid infiltrations
Queiro
et al9
2
M/76
Caucasian
White-scaled plaques in the
extensor extremities and
scalp, nummular guttate
macules on the trunk
NA
No
Fever, oral ulcer, synovitis in
both wrists, MCP joints and
right knee, dactylitis in the
second toe of the left foot, and
the forth toe of the right foot
Mild arthralgia involving
hand and wrist joints with
swelling if multiple digits
Dudelzak
et al10
3
M/60
Taiwanese
Multiple guttate whitescaled papules/plaques
over the trunk, back, and
four extremities
High grade
No
Etanercept 50 mg twice weekly. A
twice-daily application of
halobetasol ointment to the body,
betamethasone valerate solution to
the scalp, and calcipotriene solution
to the scalp and body plaques
Narrow-band UV-B phototherapy.
A twice-daily application of
diflucortolone valerate cream
No fever or arthralgia was
noted; relapsed after
following BCG instillation
Present
case
MCP ¼ metacarpophalangeal; NA ¼ not available; NSAIDs ¼ non-steroidal anti-inflammatory drugs.
which is hypothesized to be responsible for the destruction of
tumor cells. The complications of BCG immunotherapy range from
irritative lower urinary tract symptoms to sepsis. The side effects
include granulomatous prostatitis, epididymo-orchitis, hepatitis,
and pneumonitis.6 Several cutaneous side effects have also been
reported, with two case reports describing the development of
granulomatous lesions of the penis accompanied with penile
swelling and edema, painful ulcers and papules, and inguinal
lymphadenopathy after six instillations of BCG treatment.7,8 The
mycobacterial stain and cultures of both cases were negative, but
both were treated successfully with antitubercular regimens.
The other rare cutaneous complication that has been reported is
psoriasis, of which only two cases have been described in the
literature (Table 1).9,10 In 1995, Queiro et al9 first reported the
exacerbation of psoriatic polyarthropathy with dactylitis in a 52year-old man with psoriasis following BCG immunotherapy. After
suspension of BCG treatment, the patient was successfully treated
with non-steroidal anti-inflammatory drugs and steroid infiltrations. In 2008, Dudelzak et al10 reported the first case of new-onset
psoriasis and psoriatic arthritis after instillation of BCG. With
treatment of etanercept and topical steroids, the patient’s symptoms significantly improved. In the case of new-onset guttate
psoriasis following intravesical BCG immunotherapy reported here,
the patient was successfully treated with topical steroids and
narrow-band UV-B phototherapy but experienced relapse after
resumption of BCG instillation.
The relationship between guttate psoriasis and intravesical BCG
instillation remains uncertain, with the activated immune system
hypothesized to play an important role in psoriasis pathogenesis.
The mechanism by which intravesical BCG treats bladder cancer is
a complex process that is also not completely understood. Based on
the knowledge that BCG particles are internalized and processed by
antigen-presenting cells and tumor cells, it is hypothesized that
BCG antigens are present on the cell surface where, via major
histocompatibility complex molecules, they activate T lymphocytes.11 Such activation may induce inflammation, which in turn
induces the production of several cytokines, including interferongamma, tumor necrosis factor-beta, and interleukin (IL)-1, 2, 5, 6,
8, 10, 12, and 18.11,12 IL-6 production and BCG internalization
relate to the differentiation of the tumor cells.13 In contrast to the
well-differentiated transitional cell carcinoma (TCC) cells, the
poorly differentiated cell lines have been found to allow them to
internalize BCG and up-regulate IL-6 synthesis. This finding
correlates with the clinical observation of a lower recurrence rate
of high-grade TCC with BCG instillation compared to low-grade
TCC.14,15
IL-6 has been found to induce not only differentiation of Th17
cells but also production of IL-22 from naïve T cells.16,17 In addition
to the finding that IL-22 induces the proliferation of keratinocytes
and activates Stat-3 with nuclear localization and production of
psoriasin (S100A7),18,19 both Th17 and IL-22 play important roles in
the pathogenesis of psoriasis. In the present case, activated
phospho-Stat-3 was found in the nuclei of keratinocytes in the skin
lesion (Figure 3A), and psoriasin was strongly stained in the entire
epidermis of lesional skin (Figure 3B). Both findings may suggest an
activation of IL-22 in the psoriatic plaque of our patient.
In conclusion, we report a case of guttate psoriasis after the
intravesical BCG instillation for the treatment of urothelial carcinoma of the bladder. He was treated successfully with narrow-band
UV-B phototherapy and topical corticosteroids. Nowadays, use of
intravesical BCG immunotherapy for the superficial bladder cancer
is quite common. Dermatologists should be aware of this potential
cutaneous complication of BCG therapy.
References
1. Osborne GE, Mallon E, Mayou SC. Juvenile sarcoidosis after BCG vaccination.
J Am Acad Dermatol 2003;48:S99e102.
2. Gasior-Chrzan B. Delayed granulomatous lesion at the bacillus CalmetteeGuerin vaccination site. Acta Derm Venereol 2001;81:302e4.
3. Nicol M, Eley B, Kibel M, et al. Intradermal BCG vaccinationdadverse reactions
and their management. S Afr Med J 2002;92:39e42.
4. Raaschou-Nielsen W. Psoriasis vaccinalis; report of two cases, one following
B.C.G. vaccination and one following vaccination against influenza. Acta Derm
Venereol 1955;35:37e42.
5. Koca R, Altinyazar HC, Numanoglu G, et al. Guttate psoriasis-like lesions
following BCG vaccination. J Trop Pediatr 2004;50:178e9.
6. Lamm DL, van der Meijden PM, Morales A, et al. Incidence and treatment of
complications of bacillus CalmetteeGuerin intravesical therapy in superficial
bladder cancer. J Urol 1992;147:596e600.
7. Kureshi F, Kalaaji AN, Halvorson L, et al. Cutaneous complications of intravesical treatments for bladder cancer: granulomatous inflammation of the
penis following BCG therapy and penile gangrene following mitomycin
therapy. J Am Acad Dermatol 2006;55:328e31.
8. Yates J, Stein B. Bladder and penile lesions with inguinal adenopathy after
intravesical Bacillus CalmetteeGuerin (BCG) treatment. Urology 2007;70:
1123.e15e7.
9. Queiro R, Ballina J, Weruaga A, et al. Psoriatic arthropathy after BCG immunotherapy for bladder carcinoma. Br J Rheumatol 1995;34:1097.
10. Dudelzak J, Curtis AR, Sheehan DJ, et al. New-onset psoriasis and psoriatic
arthritis in a patient treated with Bacillus CalmetteeGuerin (BCG) immunotherapy. J Drugs Dermatol 2008;7:684.
11. Bevers RF, Kurth KH, Schamhart DH. Role of urothelial cells in BCG immunotherapy for superficial bladder cancer. Br J Cancer 2004;91:607e12.
12. Bohle A, Brandau S. Immune mechanisms in bacillus CalmetteeGuerin
immunotherapy for superficial bladder cancer. J Urol 2003;170:964e9.
13. Bevers RF, de Boer EC, Kurth KH, et al. BCG-induced interleukin-6 upregulation
and BCG internalization in well and poorly differentiated human bladder
cancer cell lines. Eur Cytokine Netw 1998;9:181e6.
C.-T. Hung et al. / Dermatologica Sinica 30 (2012) 108e111
14. Melekos MD, Chionis H, Pantazakos A, et al. Intravesical bacillus CalmetteeGuerin immunoprophylaxis of superficial bladder cancer: results of
a controlled prospective trial with modified treatment schedule. J Urol
1993;149:744e8.
15. Kurth KH, Bouffioux C, Sylvester R, et al. Treatment of superficial bladder
tumors: achievements and needs. The EORTC Genitourinary Group. Eur Urol
2000;37:1e9.
16. Zheng Y, Danilenko DM, Valdez P, et al. Interleukin-22, a T(H)17 cytokine,
mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007;
445:648e51.
111
17. Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the
generation of pathogenic effector TH17 and regulatory T cells. Nature
2006;441:235e8.
18. Wolk K, Witte E, Wallace E, et al. IL-22 regulates the expression of genes
responsible for antimicrobial defense, cellular differentiation, and mobility in
keratinocytes: a potential role in psoriasis. Eur J Immunol 2006;36:1309e23.
19. Sa SM, Valdez PA, Wu J, et al. The effects of IL-20 subfamily cytokines on
reconstituted human epidermis suggest potential roles in cutaneous innate
defense and pathogenic adaptive immunity in psoriasis. J Immunol 2007;178:
2229e40.