doi: 10.1111/1346-8138.12948
Journal of Dermatology 2015; 42: 992–995
CONCISE COMMUNICATION
Mycobacterium haemophilum infection with prominent facial manifestation mimicking leprosy Kentaro ISHII,1 Norihisa ISHII,2 Kazue NAKANAGA,2 Kazuaki NAKANO,3 Ikuo SAITO,4 Akihiko ASAHINA1,5 1
Department of Dermatology, National Hospital Organization Sagamihara National Hospital, Kanagawa, 2Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Departments of 3Clinical Laboratory, 4Pathology, National Hospital Organization Sagamihara National Hospital, Kanagawa, 5Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan
ABSTRACT Mycobacterium haemophilum is a slow-growing non-tuberculous mycobacterium that is rarely known to cause human skin infection, particularly in immunocompromised patients. We recently experienced a 69-year-old Japanese woman with this infection who had been under immunosuppressive treatment for recalcitrant rheumatoid arthritis. The patient showed disseminated erythematous plaques and subcutaneous nodules on the face and extremities, and interestingly, the face manifested with a striking “facies leontina” appearance. Biopsy revealed abscess and granulomatous dermatitis with the involvement of peripheral nerve bundles and the presence of innumerable acid-fast bacilli, thus necessitating differentiation from lepromatous leprosy. M. haemophilum was identified by molecular characterization as well as by successful culture with iron supplements. Although drug susceptibility testing indicated responsiveness to multiple antibiotics administrated simultaneously for the treatment, it took over 6 months to achieve significant improvement, and we also employed concurrent oral potassium iodide administration and repeated surgical excision. This case highlights the importance of continuous combination therapy for successful outcome in this rare infection. Furthermore, application of potassium iodide for mycobacterial infection warrants further evaluation by accumulating more cases.
Key words:
immunosuppression, leprosy, Mycobacterium haemophilum, potassium iodide, treatment.
INTRODUCTION Mycobacterium haemophilum is a slow-growing, non-tuberculous mycobacterium that is rarely known to cause human skin infection, particularly in immunocompromised patients.1 We recently experienced a unique Japanese case with this infection characterized by clinical and histopathological features similar to those of leprosy. We used the combination therapy with multiple antibiotics, potassium iodide (KI) and repeated surgical excision to achieve significant improvement.
CASE REPORT A 69-year-old Japanese woman visited our hospital because of high fever and erythema on the face. She had been suffering from recalcitrant rheumatoid arthritis (RA) for 17 years, and had been treated with prednisolone (PSL), methotrexate (MTX), and tumor necrosis factor-a inhibitors. She had a history of MTXassociated diffuse large B-cell lymphoma (DLBCL) 3 years previously, which showed complete remission after withdrawal of MTX and adalimumab. The condition of RA then deteriorated gradually, and MTX was again initiated 2 years previously and
increased to 12 mg/week, followed by the addition of tacrolimus 2 mg/day with an increase of the dose of PSL to 7 mg/ day. On our initial examination, she presented with edematous erythema on the forehead, nose and cheek, together with disseminated tender erythematous plaques on the lower legs (Fig. 1a). The serum C-reactive protein level was elevated (4.53 mg/dL; normal, ≤0.4). The possibility of the recurrence of DLBCL was initially suspected, and MTX and tacrolimus were stopped, while the dose of PSL was increased to 10 mg/day. The skin biopsy from the forehead showed inflammatory granuloma without caseation necrosis (Fig. 2a), and peripheral nerve bundles were involved in some areas (Fig. 2b). DLBCL was finally excluded by immunohistochemical staining. Tissue culture was negative for bacteria and fungi, and cephem antibiotics administrated for 2 weeks had no effect. Subsequent biopsies from the forehead and the upper arm, as well as the smear from the nasal mucosa, revealed the presence of numerous acid-fast bacilli by Ziehl–Neelsen staining (Fig. 2c). Mycobacterium tuberculosis and Mycobacterium avium complex were negative by molecular genetic analyses using polymerase chain reaction (PCR) and DNA–DNA hybridization technique. Although lepromatous leprosy was considered as a
Correspondence: Akihiko Asahina, M.D., Department of Dermatology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minatoku, Tokyo 105-8461, Japan. Email: [email protected] Received 22 February 2015; accepted 6 April 2015.
992
© 2015 Japanese Dermatological Association
M. haemophilum infection mimicking leprosy
(a)
(b)
(c)
(d)
Figure 1. Clinical manifestations. (a) Infiltrated erythema and swelling on the face. (b) “Facies leontina”-like appearance after 3 months of the treatment. (c) Multiple subcutaneous nodules with abscess formation on the extremities after 5 months of the treatment. (d) Clinical improvement after 8 months of the treatment.
© 2015 Japanese Dermatological Association
993
K. Ishii et al.
(a)
(b)
(c)
Figure 2. Histopathological findings. (a) Inflammatory granulomatous dermatitis without caseation necrosis in the dermis (hematoxylin–eosin [HE], original magnification 9100). (b) The involvement of peripheral nerve bundles (HE, 9400). (c) Innumerable acid-fast bacilli in the granuloma (Ziehl–Neelsen, 91000).
differential diagnosis, a split-skin smear from the earlobe was negative. She showed neither thickening of peripheral nerves nor sensory impairment. M. haemophilum was finally identified by PCR amplification and direct sequencing of hsp65, rpoB and 16S rRNA genes using the skin biopsy specimen,2 and the possibility of Mycobacterium leprae infection was excluded. Systemic involvement was not found by thorough examinations. We started treatment with the combination of oral clarithromycin (CAM) 800 mg/day, levofloxacin (LVFX) 500 mg/day and rifampicin (RFP) 450 mg/day. The activity of RA was controlled by the addition of bucillamine 100 mg/day and sulfasalazine 1000 mg/day. The cutaneous manifestations failed to improve, however, and 3 months later, she appeared as “facies leontina” (Fig. 1b). We exchanged LVFX for ciprofloxacin 400 mg/ day, and added amikacin (AMK) 300 mg/day, which was then tapered to 300 mg/2 days because of mild renal dysfunction. These regimens showed only partial and transient improvement, and multiple subcutaneous nodules continued to emerge on her extremities with recurrent fever (Fig. 1c). We then removed the majority of nodules by repeated excision, which showed epithelioid cell granuloma with or without abscess for-
mation. We started KI 0.9 g/day, and gradually tapered the dose of PSL to 7 mg/day. These treatment regimens finally led to clinical improvement (Fig. 1d), and acid-fast bacilli were not found by biopsy of the residual erythema on the face. The result of drug susceptibility testing3 for the isolated and cultured mycobacteria was revealed later as shown in Table 1. Subcutaneous nodules still emerged occasionally on the extremities, but much less frequently than before.
DISCUSSION Mycobacterium haemophilum is a slow-growing non-tuberculous mycobacterium frequently found in environmental habitats. This microorganism prefers a lower growth temperature (30– 32°C), similar to Mycobacterium marinum and Mycobacterium ulcerans, and it requires iron supplements for culture as a unique feature.1 M. haemophilum causes skin and soft tissue infections, mainly in immunocompromised patients, and also cervicofacial lymphadenitis in healthy children.1 Although its exact habitat has not been well defined, several observations suggest that water reservoirs are a likely source of M. haemophilum.4 In immunocompromised patients, the clinical manifes-
Table 1. Susceptibility of antibiotics in our case Breakpoints for slowly growing NTM3 Susceptible Streptomycin Ethambutol Kanamycin Rifampicin Rifabutin Ciprofloxacin Levofloxacin Clarithromycin* Ethionamide Amikacin
Intermediate
Resistant
≤2
4
≥8
≤1 ≤2 ≤1
– – 2
≥2 ≥4 ≥4
≤8
16
≥32
≤16
32
≥64
MIC 16–32 >128 8–16 0.125–0.25 0.03 NT 1 0.125–0.25 8 4–8
Susceptibility Resistant Susceptible Susceptible
Susceptible Susceptible
*Only clarithromycin is routinely reported for Mycobacterium avium complex isolates.3 MIC, minimum inhibitory concentration; NT, not tested; NTM, non-tuberculous mycobacterium.
994
© 2015 Japanese Dermatological Association
M. haemophilum infection mimicking leprosy
tations vary from localized diseases to systemic ones with cutaneous dissemination. Cutaneous lesions are found most frequently on the extremities, reflecting lower temperature in the body, and present as erythematous papules, plaques and nodules, which may progress to abscesses or ulcers.1,4–6 While there have been over 250 published cases of human M. haemophilum infection, its incidence is exceedingly rare in Japan.5 Our patient was obviously immunocompromised because of the treatment for RA, and the lesions appeared to spread systemically. Her previous medical history of MTXassociated DLBCL was also suggestive of her immunosuppressive condition, and simultaneously, this episode rendered the correct diagnosis difficult. Furthermore, the striking “facies leontina” appearance was indicative of lepromatous leprosy, and the biopsy specimen showed granulomatous dermatitis with the involvement of peripheral nerve bundles and the presence of innumerable acid-fast bacilli. Indeed, M. haemophilum and M. leprae have some common characteristics, such as 16S rRNA and rpoB genes, and cell wall composition with similar phenolic glycolipid antigens.4 Although the presence of nerve involvement favors the diagnosis of leprosy, a case of M. haemophilum infection on the thigh, with granulomatous involvement of a nerve bundle, has recently been reported.6 Very interestingly, there is a single report of co-infection with M. haemophilum and M. leprae in the same patient,7 but our patient never had a chance to get infected with M. leprae in Japan, and molecular analyses argued against this possibility. Sensory disturbances serve as a clue to differentiate these two conditions. Decreased sensitivity and sequential alterations of thermal, painful and tactile sensitivity are typical manifestations in leprosy, but not in M. haemophilum infection. However, up to 30% cases of leprosy may be devoid of non-anesthetic lesions.8 In particular, in lepromatous leprosy, skin lesions tend to be multiple and symmetrical, and the lesions may keep sensation in comparison with those in other types of leprosy.9 Clinical manifestations of M. haemophilum infection may also depend on immune responses, as observed in leprosy. Clear identification of M. haemophilum infection can be achieved by culture supplemented with iron. Because its visible growth may take as long as 8 weeks, molecular detection of mycobacterial DNA by PCR is very useful for rapid and accurate diagnosis.1 The mainstay of treatment for M. haemophilum infection is to employ multiple antibiotics. Combination of CAM, fluoroquinolone and one of the rifamycins is recommended for a duration of 12–24 months.1,4 Unresponsiveness to an oral regimen could warrant the addition of i.v. AMK.1 In our case, the combination of four antibiotics failed to show effectiveness even after 5 months of the initiation of treatment, although drug susceptibility testing showed sensitivity to RFP, CAM and AMK (Table 1). Significant improvement was achieved only after removal of subcutaneous nodules by repeated excision, the addition of KI and the decrease of the dose of PSL. Indeed, because our case showed numerous mycobacteria in the lesional skin, a certain length of time should be necessary for successful treatment. Curative surgical excision is a possi-
© 2015 Japanese Dermatological Association
ble option in cases with few infected sites,1 but even in our case, this approach probably helped lessen the burden of mycobacteria. Furthermore, the benefit of KI needs to be mentioned. KI has been used in the treatment of some infections, including a few cases of mycobacterium infection in Japan.10,11 It has no microbicidal activity in vitro and, therefore, interaction with the immune response of the host by activation of macrophages has been assumed to be responsible for its effect.12 Cell lysis may be another possible mechanism of action, because it has been shown to occur when Sporothrix schenckii yeast is exposed to increasing concentrations of the drug through the release of lysosomal enzymes.13 In our case, it is only speculative regarding to what extent KI was helpful in improving her condition. The effect of KI warrants further evaluation by accumulating more cases of mycobacterial infection.
CONFLICT OF INTEREST:
None declared.
REFERENCES 1 Kelley CF, Armstrong WS, Eaton ME. Disseminated Mycobacterium haemophilum infection. Lancet Infect Dis 2011; 11: 571–578. 2 Nakanaga K, Hoshino Y, Yotsu RR, Makino M, Ishii N. Laboratory procedures for the detection and identification of cutaneous nontuberculous mycobacterial infections. J Dermatol 2013; 40: 151– 159. 3 Woods GL, Brown-Elliott BA, Conville PS et al. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard, 2nd edn. The clinical and laboratory standards institute (CLSI), Wayne, PA; Document No.M24-A2, 2011. 4 Lindeboom JA, Bruijnesteijn van Coppenraet LE, van Soolingen D, Prins JM, Kuijper EJ. Clinical manifestations, diagnosis, and treatment of Mycobacterium haemophilum infections. Clin Microbiol Rev 2011; 24: 701–717. 5 Takeo N, Hatano Y, Okamoto O et al. Case of Mycobacterium haemophilum infection in a Japanese renal transplant patient and a review of Japanese cases. J Dermatol 2012; 39: 968–969. 6 Copeland NK, Arora NS, Ferquson TM. Mycobacterium haemophilum masquerading as leprosy in a renal transplant patient. Case Rep Dermatol Med 2013; 2013: 793127. 7 SoRelle JA, Beal SG, Scollard DM et al. Mycobacterium leprae and Mycobacterium haemophilum co-infection in an iatrogenically immunosuppressed patient. Diagn Microbiol Infect Dis 2014; 78: 494– 496. 8 Britton WJ, Lockwood DN. Leprosy. Lancet 2004; 363: 1209–1219. 9 Lastoria JC, Abreu MA. Leprosy: review of the epidemiological, clinical, and etiopathogenic aspects – part1. An Bras Dermal 2014; 89: 205–218. 10 Onouchi H, Nitta Y. Cutaneous mycobacterium chelonea subsp. infection in a ten-year-old boy. Rinsho Derma (Tokyo) 2003; 45: 375–377 (in Japanese). 11 Arai H, Nakajima H, Nagai R, Kaminaga Y, Mizoguchi S. A case of Mycobacterium chelonei infection of the skin. Jpn J Clin Dermatol 1983; 37: 249–253. (in Japanese). 12 Hassan I, Keen A. Potassium iodide in dermatology. Indian J Dermatol Venereol Leprol 2012; 78: 390–393. 13 Costa RO, Macedo PM, Carvalhal A, Bernardes-Engemann AR. Use of potassium iodide in dermatology: updates on an old drug. An Bras Dermatol 2013; 88: 396–402.
995
Journal of Dermatology 2015; 42: 992–995
CONCISE COMMUNICATION
Mycobacterium haemophilum infection with prominent facial manifestation mimicking leprosy Kentaro ISHII,1 Norihisa ISHII,2 Kazue NAKANAGA,2 Kazuaki NAKANO,3 Ikuo SAITO,4 Akihiko ASAHINA1,5 1
Department of Dermatology, National Hospital Organization Sagamihara National Hospital, Kanagawa, 2Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Departments of 3Clinical Laboratory, 4Pathology, National Hospital Organization Sagamihara National Hospital, Kanagawa, 5Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan
ABSTRACT Mycobacterium haemophilum is a slow-growing non-tuberculous mycobacterium that is rarely known to cause human skin infection, particularly in immunocompromised patients. We recently experienced a 69-year-old Japanese woman with this infection who had been under immunosuppressive treatment for recalcitrant rheumatoid arthritis. The patient showed disseminated erythematous plaques and subcutaneous nodules on the face and extremities, and interestingly, the face manifested with a striking “facies leontina” appearance. Biopsy revealed abscess and granulomatous dermatitis with the involvement of peripheral nerve bundles and the presence of innumerable acid-fast bacilli, thus necessitating differentiation from lepromatous leprosy. M. haemophilum was identified by molecular characterization as well as by successful culture with iron supplements. Although drug susceptibility testing indicated responsiveness to multiple antibiotics administrated simultaneously for the treatment, it took over 6 months to achieve significant improvement, and we also employed concurrent oral potassium iodide administration and repeated surgical excision. This case highlights the importance of continuous combination therapy for successful outcome in this rare infection. Furthermore, application of potassium iodide for mycobacterial infection warrants further evaluation by accumulating more cases.
Key words:
immunosuppression, leprosy, Mycobacterium haemophilum, potassium iodide, treatment.
INTRODUCTION Mycobacterium haemophilum is a slow-growing, non-tuberculous mycobacterium that is rarely known to cause human skin infection, particularly in immunocompromised patients.1 We recently experienced a unique Japanese case with this infection characterized by clinical and histopathological features similar to those of leprosy. We used the combination therapy with multiple antibiotics, potassium iodide (KI) and repeated surgical excision to achieve significant improvement.
CASE REPORT A 69-year-old Japanese woman visited our hospital because of high fever and erythema on the face. She had been suffering from recalcitrant rheumatoid arthritis (RA) for 17 years, and had been treated with prednisolone (PSL), methotrexate (MTX), and tumor necrosis factor-a inhibitors. She had a history of MTXassociated diffuse large B-cell lymphoma (DLBCL) 3 years previously, which showed complete remission after withdrawal of MTX and adalimumab. The condition of RA then deteriorated gradually, and MTX was again initiated 2 years previously and
increased to 12 mg/week, followed by the addition of tacrolimus 2 mg/day with an increase of the dose of PSL to 7 mg/ day. On our initial examination, she presented with edematous erythema on the forehead, nose and cheek, together with disseminated tender erythematous plaques on the lower legs (Fig. 1a). The serum C-reactive protein level was elevated (4.53 mg/dL; normal, ≤0.4). The possibility of the recurrence of DLBCL was initially suspected, and MTX and tacrolimus were stopped, while the dose of PSL was increased to 10 mg/day. The skin biopsy from the forehead showed inflammatory granuloma without caseation necrosis (Fig. 2a), and peripheral nerve bundles were involved in some areas (Fig. 2b). DLBCL was finally excluded by immunohistochemical staining. Tissue culture was negative for bacteria and fungi, and cephem antibiotics administrated for 2 weeks had no effect. Subsequent biopsies from the forehead and the upper arm, as well as the smear from the nasal mucosa, revealed the presence of numerous acid-fast bacilli by Ziehl–Neelsen staining (Fig. 2c). Mycobacterium tuberculosis and Mycobacterium avium complex were negative by molecular genetic analyses using polymerase chain reaction (PCR) and DNA–DNA hybridization technique. Although lepromatous leprosy was considered as a
Correspondence: Akihiko Asahina, M.D., Department of Dermatology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minatoku, Tokyo 105-8461, Japan. Email: [email protected] Received 22 February 2015; accepted 6 April 2015.
992
© 2015 Japanese Dermatological Association
M. haemophilum infection mimicking leprosy
(a)
(b)
(c)
(d)
Figure 1. Clinical manifestations. (a) Infiltrated erythema and swelling on the face. (b) “Facies leontina”-like appearance after 3 months of the treatment. (c) Multiple subcutaneous nodules with abscess formation on the extremities after 5 months of the treatment. (d) Clinical improvement after 8 months of the treatment.
© 2015 Japanese Dermatological Association
993
K. Ishii et al.
(a)
(b)
(c)
Figure 2. Histopathological findings. (a) Inflammatory granulomatous dermatitis without caseation necrosis in the dermis (hematoxylin–eosin [HE], original magnification 9100). (b) The involvement of peripheral nerve bundles (HE, 9400). (c) Innumerable acid-fast bacilli in the granuloma (Ziehl–Neelsen, 91000).
differential diagnosis, a split-skin smear from the earlobe was negative. She showed neither thickening of peripheral nerves nor sensory impairment. M. haemophilum was finally identified by PCR amplification and direct sequencing of hsp65, rpoB and 16S rRNA genes using the skin biopsy specimen,2 and the possibility of Mycobacterium leprae infection was excluded. Systemic involvement was not found by thorough examinations. We started treatment with the combination of oral clarithromycin (CAM) 800 mg/day, levofloxacin (LVFX) 500 mg/day and rifampicin (RFP) 450 mg/day. The activity of RA was controlled by the addition of bucillamine 100 mg/day and sulfasalazine 1000 mg/day. The cutaneous manifestations failed to improve, however, and 3 months later, she appeared as “facies leontina” (Fig. 1b). We exchanged LVFX for ciprofloxacin 400 mg/ day, and added amikacin (AMK) 300 mg/day, which was then tapered to 300 mg/2 days because of mild renal dysfunction. These regimens showed only partial and transient improvement, and multiple subcutaneous nodules continued to emerge on her extremities with recurrent fever (Fig. 1c). We then removed the majority of nodules by repeated excision, which showed epithelioid cell granuloma with or without abscess for-
mation. We started KI 0.9 g/day, and gradually tapered the dose of PSL to 7 mg/day. These treatment regimens finally led to clinical improvement (Fig. 1d), and acid-fast bacilli were not found by biopsy of the residual erythema on the face. The result of drug susceptibility testing3 for the isolated and cultured mycobacteria was revealed later as shown in Table 1. Subcutaneous nodules still emerged occasionally on the extremities, but much less frequently than before.
DISCUSSION Mycobacterium haemophilum is a slow-growing non-tuberculous mycobacterium frequently found in environmental habitats. This microorganism prefers a lower growth temperature (30– 32°C), similar to Mycobacterium marinum and Mycobacterium ulcerans, and it requires iron supplements for culture as a unique feature.1 M. haemophilum causes skin and soft tissue infections, mainly in immunocompromised patients, and also cervicofacial lymphadenitis in healthy children.1 Although its exact habitat has not been well defined, several observations suggest that water reservoirs are a likely source of M. haemophilum.4 In immunocompromised patients, the clinical manifes-
Table 1. Susceptibility of antibiotics in our case Breakpoints for slowly growing NTM3 Susceptible Streptomycin Ethambutol Kanamycin Rifampicin Rifabutin Ciprofloxacin Levofloxacin Clarithromycin* Ethionamide Amikacin
Intermediate
Resistant
≤2
4
≥8
≤1 ≤2 ≤1
– – 2
≥2 ≥4 ≥4
≤8
16
≥32
≤16
32
≥64
MIC 16–32 >128 8–16 0.125–0.25 0.03 NT 1 0.125–0.25 8 4–8
Susceptibility Resistant Susceptible Susceptible
Susceptible Susceptible
*Only clarithromycin is routinely reported for Mycobacterium avium complex isolates.3 MIC, minimum inhibitory concentration; NT, not tested; NTM, non-tuberculous mycobacterium.
994
© 2015 Japanese Dermatological Association
M. haemophilum infection mimicking leprosy
tations vary from localized diseases to systemic ones with cutaneous dissemination. Cutaneous lesions are found most frequently on the extremities, reflecting lower temperature in the body, and present as erythematous papules, plaques and nodules, which may progress to abscesses or ulcers.1,4–6 While there have been over 250 published cases of human M. haemophilum infection, its incidence is exceedingly rare in Japan.5 Our patient was obviously immunocompromised because of the treatment for RA, and the lesions appeared to spread systemically. Her previous medical history of MTXassociated DLBCL was also suggestive of her immunosuppressive condition, and simultaneously, this episode rendered the correct diagnosis difficult. Furthermore, the striking “facies leontina” appearance was indicative of lepromatous leprosy, and the biopsy specimen showed granulomatous dermatitis with the involvement of peripheral nerve bundles and the presence of innumerable acid-fast bacilli. Indeed, M. haemophilum and M. leprae have some common characteristics, such as 16S rRNA and rpoB genes, and cell wall composition with similar phenolic glycolipid antigens.4 Although the presence of nerve involvement favors the diagnosis of leprosy, a case of M. haemophilum infection on the thigh, with granulomatous involvement of a nerve bundle, has recently been reported.6 Very interestingly, there is a single report of co-infection with M. haemophilum and M. leprae in the same patient,7 but our patient never had a chance to get infected with M. leprae in Japan, and molecular analyses argued against this possibility. Sensory disturbances serve as a clue to differentiate these two conditions. Decreased sensitivity and sequential alterations of thermal, painful and tactile sensitivity are typical manifestations in leprosy, but not in M. haemophilum infection. However, up to 30% cases of leprosy may be devoid of non-anesthetic lesions.8 In particular, in lepromatous leprosy, skin lesions tend to be multiple and symmetrical, and the lesions may keep sensation in comparison with those in other types of leprosy.9 Clinical manifestations of M. haemophilum infection may also depend on immune responses, as observed in leprosy. Clear identification of M. haemophilum infection can be achieved by culture supplemented with iron. Because its visible growth may take as long as 8 weeks, molecular detection of mycobacterial DNA by PCR is very useful for rapid and accurate diagnosis.1 The mainstay of treatment for M. haemophilum infection is to employ multiple antibiotics. Combination of CAM, fluoroquinolone and one of the rifamycins is recommended for a duration of 12–24 months.1,4 Unresponsiveness to an oral regimen could warrant the addition of i.v. AMK.1 In our case, the combination of four antibiotics failed to show effectiveness even after 5 months of the initiation of treatment, although drug susceptibility testing showed sensitivity to RFP, CAM and AMK (Table 1). Significant improvement was achieved only after removal of subcutaneous nodules by repeated excision, the addition of KI and the decrease of the dose of PSL. Indeed, because our case showed numerous mycobacteria in the lesional skin, a certain length of time should be necessary for successful treatment. Curative surgical excision is a possi-
© 2015 Japanese Dermatological Association
ble option in cases with few infected sites,1 but even in our case, this approach probably helped lessen the burden of mycobacteria. Furthermore, the benefit of KI needs to be mentioned. KI has been used in the treatment of some infections, including a few cases of mycobacterium infection in Japan.10,11 It has no microbicidal activity in vitro and, therefore, interaction with the immune response of the host by activation of macrophages has been assumed to be responsible for its effect.12 Cell lysis may be another possible mechanism of action, because it has been shown to occur when Sporothrix schenckii yeast is exposed to increasing concentrations of the drug through the release of lysosomal enzymes.13 In our case, it is only speculative regarding to what extent KI was helpful in improving her condition. The effect of KI warrants further evaluation by accumulating more cases of mycobacterial infection.
CONFLICT OF INTEREST:
None declared.
REFERENCES 1 Kelley CF, Armstrong WS, Eaton ME. Disseminated Mycobacterium haemophilum infection. Lancet Infect Dis 2011; 11: 571–578. 2 Nakanaga K, Hoshino Y, Yotsu RR, Makino M, Ishii N. Laboratory procedures for the detection and identification of cutaneous nontuberculous mycobacterial infections. J Dermatol 2013; 40: 151– 159. 3 Woods GL, Brown-Elliott BA, Conville PS et al. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard, 2nd edn. The clinical and laboratory standards institute (CLSI), Wayne, PA; Document No.M24-A2, 2011. 4 Lindeboom JA, Bruijnesteijn van Coppenraet LE, van Soolingen D, Prins JM, Kuijper EJ. Clinical manifestations, diagnosis, and treatment of Mycobacterium haemophilum infections. Clin Microbiol Rev 2011; 24: 701–717. 5 Takeo N, Hatano Y, Okamoto O et al. Case of Mycobacterium haemophilum infection in a Japanese renal transplant patient and a review of Japanese cases. J Dermatol 2012; 39: 968–969. 6 Copeland NK, Arora NS, Ferquson TM. Mycobacterium haemophilum masquerading as leprosy in a renal transplant patient. Case Rep Dermatol Med 2013; 2013: 793127. 7 SoRelle JA, Beal SG, Scollard DM et al. Mycobacterium leprae and Mycobacterium haemophilum co-infection in an iatrogenically immunosuppressed patient. Diagn Microbiol Infect Dis 2014; 78: 494– 496. 8 Britton WJ, Lockwood DN. Leprosy. Lancet 2004; 363: 1209–1219. 9 Lastoria JC, Abreu MA. Leprosy: review of the epidemiological, clinical, and etiopathogenic aspects – part1. An Bras Dermal 2014; 89: 205–218. 10 Onouchi H, Nitta Y. Cutaneous mycobacterium chelonea subsp. infection in a ten-year-old boy. Rinsho Derma (Tokyo) 2003; 45: 375–377 (in Japanese). 11 Arai H, Nakajima H, Nagai R, Kaminaga Y, Mizoguchi S. A case of Mycobacterium chelonei infection of the skin. Jpn J Clin Dermatol 1983; 37: 249–253. (in Japanese). 12 Hassan I, Keen A. Potassium iodide in dermatology. Indian J Dermatol Venereol Leprol 2012; 78: 390–393. 13 Costa RO, Macedo PM, Carvalhal A, Bernardes-Engemann AR. Use of potassium iodide in dermatology: updates on an old drug. An Bras Dermatol 2013; 88: 396–402.
995
