10 Velasco S, Guillet G. Improvement of Darier’s disease on treatment with topical 5-fluorouracil. Ann Dermatol Venereol 2006; 133:366–8.
Key words: 5-fluorouracil, Darier disease, treatment
Conflicts of interest: none declared.
Chronic hepatitis B reactivation and systemic
glucocorticosteroid therapy
DOI: 10.1111/j.1365-2133.2008.08558.x
SIR, We read with interest the article by Yang et al.1in a recent
issue of the Journal in which they retrospectively reviewed patients with pemphigus vulgaris and dermatomyositis treated with immunosuppressive therapies including systemic gluco-corticosteroid (GC). In the article, the authors suggested that four of 98 patients had developed hepatitis because of GC-induced hepatitis B virus (HBV) reactivation. The observa-tion is quite informative and is particularly important to those patients in HBV-endemic areas requiring long-term GC ther-apy. However, the findings should be interpreted cautiously before concluding that the use of GC has led to HBV reactiva-tion directly in these patients.
HBV reactivation is characterized by a temporal relationship between the rise in viral load of HBV, biochemical hepatitis and medication use. The occurrence of hepatitis during or im-mediately after cytotoxic chemotherapy is accompanied either by a 10-fold increase in HBV DNA levels or by an absolute increase that exceeds 9 log10 copies mL)1, in the absence of
other systemic infections.2 Therefore, the baseline characteris-tics of HBV infection are essential to establish a definite diag-nosis of HBV reactivation.
The overt biochemical flares or hepatitis in the article may have alternative explanations. The diagnosis of HBV reactivation would not be definite without comparison with the baseline HBV DNA level, as the possibility of silent viraemia before treat-ment cannot be ruled out. Further, a single elevation of HBV DNA level alone does not guarantee an increment of the level. Besides, it is not uncommon for HBV carriers to develop spon-taneous flares – the incidence may be up to 32%3– and the use of GC in this setting could possibly be coincidental.
Based on the observation of this case series, Yang et al. rec-ommended concurrent use of antiviral agents in chronic HBV carriers receiving long-term immunosuppressive therapy. Current practices are mostly derived from the experience of cancer patients receiving chemotherapy. In a study of Chinese patients with lymphoma, 27% were found to be seropositive for hepatitis B surface antigen. Of these patients, 47% devel-oped reactivation of HBV during chemotherapy and this resulted in 5% mortality.4 A study by Nakamura et al. of Japanese patients with lymphoma reported that only 3Æ3% of the patients had chronic HBV infection, but the incidence of severe hepatitis was found to be 53%, which was associated with a mortality rate of 24%.5Thus, preventing HBV
reactiva-tion in HBV carriers with lamivudine has been advocated in patients with haematological malignancies treated with chemo-therapy.6 However, little is known whether universal use of antiviral agents pre-emptively is indicated in noncancer patients under immunosuppressive or GC treatment because the antiviral agents are not panaceas. Prolonged use of lamivu-dine can decrease hepatitis flares. However, drug-resistant strains of HBV are an emerging problem (15% per year with lamivudine use).7 Therefore, identification of high-risk groups for HBV reactivation is important before starting immuno-suppressive therapy. The risk factors identified in cancer patients receiving chemotherapy include male gender, young age, diagnosis of lymphoma or breast cancer, seropositive hepatitis B envelope antigen, high pretreatment HBV DNA level, use of GC and high cumulative dose of GC.8–10In the article by Yanget al., the proportion of HBV-infected patients in the study group was lacking.
We congratulate Yang et al. for this first report of possible HBV reactivation in dermatological patients on long-term GC. However, more studies are needed to draw a clear picture on this issue, such as the incidence, rate of severe complications and specific risk factors for HBV reactivation in this group of patients. At this moment, we cannot advocate the pre-emptive use of antiviral agents in these patients. For early detection of possible complications, we can screen the baseline HBV status and regularly monitor the liver function of these patients. When necessary, it is best for us to work in conjuction with gastroenterologists on this emerging problem.
C - C . WA N G
S - Y . WA N G* T - H . TS A I
Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan
*Division of Gastroenterology, Department of Medicine,
Mackay Memorial Hospital, Taipei, Taiwan
Department of Dermatology, Taipei Medical University, Wan Fang Hospital, No. 111, Section 3,
Singlong Road, Taipei 116, Taiwan Correspondence: Tsung-Hsien Tsai. E-mail: thtsai2@yahoo.com.tw
References
1 Yang C-H, Wu T-S, Chiu C-T. Chronic hepatitis B reactivation: a word of caution regarding the use of systemic glucocorticosteroid therapy. Br J Dermatol 2007; 157:587–90.
2 Yeo W, Johnson PJ. Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology 2006; 43:209–20.
3 Davis GL, Hoofnagle JH, Waggoner JG. Spontaneous reactivation of chronic hepatitis B virus infection. Gastroenterology 1984; 86:230–5. 4 Lok AS, Liang RH, Chiu EK et al. Reactivation of hepatitis B virus
replication in patients receiving cytotoxic therapy. Report of a pro-spective study. Gastroenterology 1991; 100:182–8.
5 Nakamura Y, Motokura T, Fujita A et al. Severe hepatitis related to chemotherapy in hepatitis B virus carriers with hematologic malig-nancies. Survey in Japan, 1987–1991. Cancer 1996; 78:2210–15.
2008 The Authors Journal Compilation 2008 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp1371–1401 1396 Correspondence
6 Vassiliadis T, Garipidou V, Tziomalos K et al. Prevention of hepatitis B reactivation with lamivudine in hepatitis B virus carriers with hematologic malignancies treated with chemotherapy – a prospec-tive case series. Am J Hematol 2005; 80:197–203.
7 Conjeevaram HS, Lok AS-F. Management of chronic hepatitis B [erratum appears in J Hepatol 2003; 38:876]. J Hepatol 2003; 38 (Suppl. 1):S90–103.
8 Yeo W, Chan PK, Zhong S et al. Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol 2000; 62:299–307.
9 Yeo W, Zee B, Zhong S et al. Comprehensive analysis of risk factors associating with hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Br J Cancer 2004; 90:1306–11.
10 Yi N-J, Suh K-S, Cho JY et al. Recurrence of hepatitis B is associated with cumulative corticosteroid dose and chemotherapy against hepatocellular carcinoma recurrence after liver transplantation. Liver Transpl 2007; 13:451–8.
Key words: glucocorticosteroid, hepatitis B
Conflicts of interest: none declared.
Chronic hepatitis B reactivation and systemic
glucocorticosteroid therapy: reply from authors
DOI: 10.1111/j.1365-2133.2008.08554.x
SIR, We thank Dr Wang and colleagues for their comments on
our paper on reactivation of chronic hepatitis B virus (HBV) following systemic glucocorticosteroid therapy that was pub-lished in the September 2007 issue of this Journal.1The authors raise two issues. Firstly, they question whether the hepatitis in four patients described in this article does not represent ‘reactivation’ because they do not have a baseline HBV DNA viral titre for reference, and thus cannot fit the definition of HBV reactivation. Secondly, Wanget al. question the feasibility of antiviral drug prophylaxis therapy as recommended by us.
Regarding the first issue, the published article was limited by its scope as a retrospective study. As most dermatologists have traditionally neglected the risk of HBV infection and reactivation during corticosteroid therapy, only 21 of 98 patients (21%) were screened or recorded for serum hepatitis B markers status in this retrospective study. Thus, it was not possible to acquire a baseline HBV DNA viral titre. Even without a baseline HBV DNA viral titre for comparison, however, it is reasonable to conclude that there was a reactivation of HBV in these four patients based on the clinical history and course, as prednisolone is a known risk factor for HBV reactivation, as reported previously.2
Regarding the second issue, HBV reactivation is often encountered in lymphoma patients receiving chemo ⁄ immuno-suppressive therapy. Currently, the consensus based on dif-ferent studies noting reactivation of HBV in lymphoma recommends prophylactic use of antiviral therapy and moni-toring of HBV DNA titre and liver function during lymphoma chemotherapy.3–6Certainly, more study is needed to
demon-strate the optimal intervention time of antiviral therapy in patients with HBV treated with corticosteroids, but this would entail an extensive prospective cohort, preferably a random-ized controlled trial, for definitive elucidation.
While we recognize the extensive research on the part of Wang et al., it is our opinion that the points raised in their cor-respondence had been preliminarily addressed in our previous published paper. A prospective clinical study of HBV carriers undergoing systemic corticosteroid therapy along with a rando-mized controlled trial for analysis of optimal timing of antiviral drugs use would provide much insight into the phenomenon of HBV reactivation during immunosuppressive regimens.
C - H . YA N G
C - T . CH I U* Department of Dermatology and
*Gasteroentrology and Hepatology, Chang Gung Memorial Hospital, Taipei, Taiwan
E-mail: dermadr@hotmail.com
References
1 Yang C-H, Wu T-S, Chiu C-T. Chronic hepatitis B reactivation: a word of caution regarding the use of systemic glucocorticosteroid therapy. Br J Dermatol 2007; 157:587–90.
2 Lam KC, Lai CL, Trepo C, Wu PC. Deleterious effect of prednisolone in HBsAg-positive chronic active hepatitis. N Engl J Med 1981; 304:380–6. 3 Leaw SJ, Yen CJ, Huang WT et al. Preemptive use of interferon or lamivudine for hepatitis B reactivation in patients with aggressive lymphoma receiving chemotherapy. Ann Hematol 2004; 83:270–5. 4 Law JK, Ho JK, Hoskins PJ et al. Fatal reactivation of hepatitis B
post-chemotherapy for lymphoma in a hepatitis B surface antigen-negative, hepatitis B core antibody-positive patient: potential impli-cations for future prophylaxis recommendations. Leuk Lymphoma 2005; 46:1085–9.
5 Esteve M, Saro C, Gonza´lez-Huix F et al. Chronic hepatitis B reactiva-tion following infliximab therapy in Crohn’s disease patients: need for primary prophylaxis. Gut 2004; 53:1363–5.
6 Simpson ND, Simpson PW, Ahmed AM et al. Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus infection with lamivudine. J Clin Gastroenterol 2003; 37:68–71.
Key words: glucocorticosteroid, hepatitis B
Conflicts of interest: none declared.
Unilateral segmental acneiform naevus:
a model disorder towards understanding
fibroblast growth factor receptor 2 function
in acne?
DOI: 10.1111/j.1365-2133.2008.08559.x
SIR, We present a 15-year-old boy with unilateral segmental acne on his right chest, trunk, shoulder and arm, including the extensor surface of the forearm (Fig. 1a). Multiple comedones as well as inflammatory papules and pustules were found in linear or whorled skin areas reflecting the lines of Blaschko.
2008 The Authors
Journal Compilation 2008 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp1371–1401
