Eur J Dermatol 2013; 23(5): 700-40
Correspondence
Copyright © 2017 John Libbey Eurotext. Downloaded by NYU LANGONE MED CTR SCH OF MED HEALTH SCIENCES LIBRARY on 29/03/2017.
CORRESPONDENCE
Cutaneous Mycobacterium chelonae infection in a rheumatoid arthritis patient treated with etanercept
700
D
B
C
E
Figure 1. Scaly, infiltrating erythema with pustules on the right index finger before treatment (A), 2 months (B), and 12 months after minocycline treatment (C). A skin biopsy showed massive infiltration of lymphocytes, neutrophils, monocytes and plasma cells, an abscess in the horny cell layer but no granuloma formation stained with HE (D, E). Original magnification ×40 (D) and ×200 (E).
recurrence was observed after 6 months of discontinuation of the antibiotic therapy (figure 1C). Widespread use of anti-TNF agents appears to be associated with an increasing frequency of opportunistic mycobacterial infections, including non-tuberculous mycobacterial infections. Winthrop et al. reported 49 patients with mycobacterial infection who received biologic agents and M. chelonae was identified in 5 patients [1]. The severity of M. chelonae infection varies, ranging from a local area to disseminated lesions [2, 3]. Therefore, early diagnosis and treatment are required. Diagnosis of atypical mycobacterial infection is challenging. Accumulating evidence has revealed the clinical usefulness of PCR to identify the organisms but false-positives can occur. Bacterial culture needs time to obtain results but appears essential for accurate diagnosis. Our case presented with no granuloma formation and negative Ziehl Neelsen staining in histology but bacterial culture was a decisive procedure for the diagnosis of M. chelonae, indicating that bacterial culture remains the reliable diagnostic procedure. Alternatively, a detailed history may help for diagnosis because most patients with atypical mycobacteria infection EJD, vol. 23, n◦ 5, September-October 2013
To cite this article: Hamaguchi Y, Fujimoto M, Oishi K, Kitajima S, Wada T, Takehara K. Cutaneous Mycobacterium chelonae infection in a rheumatoid arthritis patient treated with etanercept. Eur J Dermatol 2013; 23(5): 700-40 doi:10.1684/ejd.2013.2156
doi:10.1684/ejd.2013.2156
Mycobacterium chelonae (M. chelonae) is a rapidlygrowing, atypical mycobacterium that causes illness in immunosuppressed patients. Etanercept is one of the antitumor necrosis factor (anti-TNF) monoclonal antibodies and has widely been used in the treatment of autoimmune diseases, including rheumatoid arthritis. With more use of anti-TNF therapy, rare but occasionally fatal opportunistic infections have been increasing. We report a case of cutaneous M. chelonae infection in a rheumatoid arthritis patient treated with etanercept. A 44-year-old female patient presented to our outpatient clinic. She had a 4-year history of rheumatoid arthritis. Previous therapy, including methotrexate, salazosulfapyridine, bucillamine and corticosteroids had not shown sufficient clinical response. Therefore, anti-TNF therapy with etanercept was started in combination with corticosteroid, 2 years after the onset of the disease. After 2 years of etanercept therapy, the patient noticed a painful, red, swollen lesion on her right index finger. She was not aware of any traumatic events and had not been in a marine environment. She received oral antibiotics, which included cefdinir and faropenem with gentamicin ointment, but the lesion did not improve. One month after first noting the lesion, the patient was referred to our hospital. She had an erythematous, scaly infiltrating skin lesion with pustules on the right index finger (figure 1A). She was in a good general condition and laboratory findings were almost within normal ranges. Rheumatoid arthritis was in clinical remission under the etanercept therapy. A skin biopsy revealed a dense infiltration of lymphocytes, neutrophils, macrophages, and plasma cells but no apparent granuloma formation (figures 1D,E). Ziehl Neelsen staining was negative for acid fast bacilli. Bacterial culture using the biopsy sample was positive for coagulase-negative staphylococci and bacillus species, which were later proven to be a secondary infection. PCR for M. tuberculosis, M. avium and M. intracellulare were negative. Etanercept therapy was continued until the results of the mycobacterial culture became clear. An antibiotic therapy with minocycline monotherapy was started. Three weeks after the skin biopsy, the diagnosis of M. chelonae was made by bacterial culture. A detailed full-body examination revealed no other lesions. Etanercept was discontinued. Minocycline was continued and the skin lesion improved (figure 1B). After 4 months of minocycline therapy, antibiotic therapy was changed to clarithromycin. Antibiotic therapy was continued for a total of 6 months. No
A
have potentially undergone minor trauma, especially with exposure to a fish tank or a marine environment [4]. The duration and combination of the antibiotic therapy should be discussed. Combination treatments using clarithromycin are recommended and treatment should be continued for at least 1-2 months after healing of skin lesions [5, 6].
Copyright © 2017 John Libbey Eurotext. Downloaded by NYU LANGONE MED CTR SCH OF MED HEALTH SCIENCES LIBRARY on 29/03/2017.
Disclosure. Financial support: none. Conflict of interest: none. 1
Department of Dermatology, Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan 2
Yasuhito HAMAGUCHI1 Manabu FUJIMOTO1 Kyosuke OISHI1 Shinji KITAJIMA2 Takashi WADA2 Kazuhiko TAKEHARA1
1. Winthrop KL, Yamashita S, Beekmann SE, Polgreen PM. Mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor and other newly approved biologic therapies: Case finding through the emerging infections network. Clin Infect Dis 2008; 46: 1738-40. 2. Sodemoto K, Shimada Y, Nishijima C, Inaoki M. Successful treatment of cutaneous mycobacterium chelonae infection with roxithromycin. J Dermatol 2007; 34: 846-8. 3. Jankovic M, Zmak L, Krajinovic V, et al. A fatal mycobacterium chelonae infection in an immunosuppressed patient with systemic lupus erythematosus and concomitant Fahr’s syndrome. J Infect Chemother 2011; 17: 264-7. 4. Kump PK, Hogenauer C, Wenzl HH, Petritsch W. A case of opportunistic skin infection with mycobacterium marinum during adalimumab treatment in a patient with Crohn’s disease. J Crohns Colitis 2013; 7: e15-8. 5. Lamb SR, Stables GI, Merchant W. Disseminated cutaneous infection with mycobacterium chelonae in a patient with steroiddependent rheumatoid arthritis. Clin Exp Dermatol 2004; 29: 254-7. 6. Wallace RJ, Jr, Tanner D, Brennan PJ, Brown BA. Clinical trial of clarithromycin for cutaneous (disseminated) infection due to mycobacterium chelonae. Ann Intern Med 1993; 119: 482-6. doi:10.1684/ejd.2013.2156
Pigmented purpuric dermatitis with high expression levels of serum TARC/CCL17 and epidermal TSLP
is considered to be a useful biomarker for assessing disease activity [3]. Thymic stromal lymphopoietin (TSLP), which is mainly expressed by epidermal keratinocytes, is considered to be a critical inducer of Th2 inflammation [4-6]. It has been reported that the serum levels of TSLP are elevated in MF patients [7]. Although lichenoid-type PPD could be an unusual early manifestation of MF, its Th1/Th2 balance has not been examined. We report a case of lichenoid-type PPD with high expression levels of serum TARC and epidermal TSLP, which suggests a Th2 dominant condition. A 62-year-old Japanese male presented to our hospital complaining of generalized eruptions consisting of slightlyinfiltrated, coalescent, brownish-red purpuric macules and plaques, which had been evident in the lower extremities for five years (figure 1A). The patient mentioned a mild pruritic sensation. Laboratory examination revealed a high serum TARC/CCL17 level of 24,000 pg/mL (faculty normal range:
Correspondence
Copyright © 2017 John Libbey Eurotext. Downloaded by NYU LANGONE MED CTR SCH OF MED HEALTH SCIENCES LIBRARY on 29/03/2017.
CORRESPONDENCE
Cutaneous Mycobacterium chelonae infection in a rheumatoid arthritis patient treated with etanercept
700
D
B
C
E
Figure 1. Scaly, infiltrating erythema with pustules on the right index finger before treatment (A), 2 months (B), and 12 months after minocycline treatment (C). A skin biopsy showed massive infiltration of lymphocytes, neutrophils, monocytes and plasma cells, an abscess in the horny cell layer but no granuloma formation stained with HE (D, E). Original magnification ×40 (D) and ×200 (E).
recurrence was observed after 6 months of discontinuation of the antibiotic therapy (figure 1C). Widespread use of anti-TNF agents appears to be associated with an increasing frequency of opportunistic mycobacterial infections, including non-tuberculous mycobacterial infections. Winthrop et al. reported 49 patients with mycobacterial infection who received biologic agents and M. chelonae was identified in 5 patients [1]. The severity of M. chelonae infection varies, ranging from a local area to disseminated lesions [2, 3]. Therefore, early diagnosis and treatment are required. Diagnosis of atypical mycobacterial infection is challenging. Accumulating evidence has revealed the clinical usefulness of PCR to identify the organisms but false-positives can occur. Bacterial culture needs time to obtain results but appears essential for accurate diagnosis. Our case presented with no granuloma formation and negative Ziehl Neelsen staining in histology but bacterial culture was a decisive procedure for the diagnosis of M. chelonae, indicating that bacterial culture remains the reliable diagnostic procedure. Alternatively, a detailed history may help for diagnosis because most patients with atypical mycobacteria infection EJD, vol. 23, n◦ 5, September-October 2013
To cite this article: Hamaguchi Y, Fujimoto M, Oishi K, Kitajima S, Wada T, Takehara K. Cutaneous Mycobacterium chelonae infection in a rheumatoid arthritis patient treated with etanercept. Eur J Dermatol 2013; 23(5): 700-40 doi:10.1684/ejd.2013.2156
doi:10.1684/ejd.2013.2156
Mycobacterium chelonae (M. chelonae) is a rapidlygrowing, atypical mycobacterium that causes illness in immunosuppressed patients. Etanercept is one of the antitumor necrosis factor (anti-TNF) monoclonal antibodies and has widely been used in the treatment of autoimmune diseases, including rheumatoid arthritis. With more use of anti-TNF therapy, rare but occasionally fatal opportunistic infections have been increasing. We report a case of cutaneous M. chelonae infection in a rheumatoid arthritis patient treated with etanercept. A 44-year-old female patient presented to our outpatient clinic. She had a 4-year history of rheumatoid arthritis. Previous therapy, including methotrexate, salazosulfapyridine, bucillamine and corticosteroids had not shown sufficient clinical response. Therefore, anti-TNF therapy with etanercept was started in combination with corticosteroid, 2 years after the onset of the disease. After 2 years of etanercept therapy, the patient noticed a painful, red, swollen lesion on her right index finger. She was not aware of any traumatic events and had not been in a marine environment. She received oral antibiotics, which included cefdinir and faropenem with gentamicin ointment, but the lesion did not improve. One month after first noting the lesion, the patient was referred to our hospital. She had an erythematous, scaly infiltrating skin lesion with pustules on the right index finger (figure 1A). She was in a good general condition and laboratory findings were almost within normal ranges. Rheumatoid arthritis was in clinical remission under the etanercept therapy. A skin biopsy revealed a dense infiltration of lymphocytes, neutrophils, macrophages, and plasma cells but no apparent granuloma formation (figures 1D,E). Ziehl Neelsen staining was negative for acid fast bacilli. Bacterial culture using the biopsy sample was positive for coagulase-negative staphylococci and bacillus species, which were later proven to be a secondary infection. PCR for M. tuberculosis, M. avium and M. intracellulare were negative. Etanercept therapy was continued until the results of the mycobacterial culture became clear. An antibiotic therapy with minocycline monotherapy was started. Three weeks after the skin biopsy, the diagnosis of M. chelonae was made by bacterial culture. A detailed full-body examination revealed no other lesions. Etanercept was discontinued. Minocycline was continued and the skin lesion improved (figure 1B). After 4 months of minocycline therapy, antibiotic therapy was changed to clarithromycin. Antibiotic therapy was continued for a total of 6 months. No
A
have potentially undergone minor trauma, especially with exposure to a fish tank or a marine environment [4]. The duration and combination of the antibiotic therapy should be discussed. Combination treatments using clarithromycin are recommended and treatment should be continued for at least 1-2 months after healing of skin lesions [5, 6].
Copyright © 2017 John Libbey Eurotext. Downloaded by NYU LANGONE MED CTR SCH OF MED HEALTH SCIENCES LIBRARY on 29/03/2017.
Disclosure. Financial support: none. Conflict of interest: none. 1
Department of Dermatology, Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan 2
Yasuhito HAMAGUCHI1 Manabu FUJIMOTO1 Kyosuke OISHI1 Shinji KITAJIMA2 Takashi WADA2 Kazuhiko TAKEHARA1
1. Winthrop KL, Yamashita S, Beekmann SE, Polgreen PM. Mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor and other newly approved biologic therapies: Case finding through the emerging infections network. Clin Infect Dis 2008; 46: 1738-40. 2. Sodemoto K, Shimada Y, Nishijima C, Inaoki M. Successful treatment of cutaneous mycobacterium chelonae infection with roxithromycin. J Dermatol 2007; 34: 846-8. 3. Jankovic M, Zmak L, Krajinovic V, et al. A fatal mycobacterium chelonae infection in an immunosuppressed patient with systemic lupus erythematosus and concomitant Fahr’s syndrome. J Infect Chemother 2011; 17: 264-7. 4. Kump PK, Hogenauer C, Wenzl HH, Petritsch W. A case of opportunistic skin infection with mycobacterium marinum during adalimumab treatment in a patient with Crohn’s disease. J Crohns Colitis 2013; 7: e15-8. 5. Lamb SR, Stables GI, Merchant W. Disseminated cutaneous infection with mycobacterium chelonae in a patient with steroiddependent rheumatoid arthritis. Clin Exp Dermatol 2004; 29: 254-7. 6. Wallace RJ, Jr, Tanner D, Brennan PJ, Brown BA. Clinical trial of clarithromycin for cutaneous (disseminated) infection due to mycobacterium chelonae. Ann Intern Med 1993; 119: 482-6. doi:10.1684/ejd.2013.2156
Pigmented purpuric dermatitis with high expression levels of serum TARC/CCL17 and epidermal TSLP
is considered to be a useful biomarker for assessing disease activity [3]. Thymic stromal lymphopoietin (TSLP), which is mainly expressed by epidermal keratinocytes, is considered to be a critical inducer of Th2 inflammation [4-6]. It has been reported that the serum levels of TSLP are elevated in MF patients [7]. Although lichenoid-type PPD could be an unusual early manifestation of MF, its Th1/Th2 balance has not been examined. We report a case of lichenoid-type PPD with high expression levels of serum TARC and epidermal TSLP, which suggests a Th2 dominant condition. A 62-year-old Japanese male presented to our hospital complaining of generalized eruptions consisting of slightlyinfiltrated, coalescent, brownish-red purpuric macules and plaques, which had been evident in the lower extremities for five years (figure 1A). The patient mentioned a mild pruritic sensation. Laboratory examination revealed a high serum TARC/CCL17 level of 24,000 pg/mL (faculty normal range:
