Fishtank Granuloma Treated with Combination of Minocycline and

Rifampicine

Alfonsus Rendy Laksditalia Nugroho

, Taufiq Hidayat

, Lita Setyowatie

, Krisna Ariaputra

, Diah

Prabawati Retnani

Departement of Dermatology and Venereology, Faculty of Medicine, Universitas Brawijaya / dr. Saiful Anwar

Regional General Hospital, Malang, Indonesia

Department of Pathology Anatomy, Faculty of Medicine, Universitas Brawijaya / dr. Saiful Anwar Regional General

Hospital, Malang, Indonesia

Keywords: fishtank granuloma, minocycline, rifampicine

Abstract: Fishtank granuloma is atypical mycobacterium infection with Mycobacterium marinum as causative agent,

primary risk of this condition are exposure with aquatic environment. It has no standard therapy, meanwhile

it is imperative to begin therapy as soon as possible before bad prognosis happen due to ascending infection

from skin to tenosynovium.

Men, 40 years old complains from painful bumps in the back of the hand,

ulcerating and indurated. Patient had undergone several therapies, but there were no improvement. Patient

got hobby of nurturing koi fishes, similar lesion found on patient’s fishes. General examination shows pain

score was 6/10. Dermatological examination dorsal manus dextra, with localized distribution, shows

erythematous nodules, well defined, quantity 6, size 0,5–2 cm, with ulcers, crusts and scales.

Histopathological examination shows poorly formed granulation tissues. Epidermis shows acanthosis and

some absent, while dermis shows connective tissue with many blood vessels and sparse inflammatory cells

of neutrophil, lymphocyte and histiocyte. No visible datia cells and caseous necrosis. Blood count shows

limphocytosis and slight increase of ESR. Patient being diagnosed as fishtank granuloma, got minocycline

2x100 mg, rifampicine 1x600 mg for three months. Lesion healed with scar, pain score reduced to zero were

achieved in second month. Therapy continued one month after complete healing. Fishtank granuloma often

misdiagnose and leads to late initial therapy, meanwhile this infection tend to be persistent and unable to

heal spontaneously. Combination of minocycline and rifampicine can increase therapeutical efectivity and

may support establishing diagnosis of fishtank granuloma.

1 INTRODUCTION

Fishtank granuloma is atypical mycobacterial

infection with Mycobacterium marinum as causative

agent, that obtain its name due to primary risk factor

of this condition which are exposure to aquatic

environment or water creatures. (Delphine et al,

2012,Wu et al, 2002) This pathogen exist in both

tropical or sea water. Mycobacterium marinum first

time being isolated by Aronson in 1926 from a dead

sea fish that being obtained from aquarium in

Philadelphia. In 1951, Norden and Linell able to

isolating it from swimmer who swim in the

contagious swimming pool in Sweden. In the year of

1962, Swift and Cohen begin to report two cases of

Mycobacterium marinum infection from tropical

fishes aquarium, and so it begin the term “fishtank

granuloma.” Since that time, the term “swimming

pool granuloma” has rarely being used because

chlorination of this reservoir make this condition

become rare to occur in swimming pool.(Bonamonte

et al, 2013) Mycobacterium marinum infection in

human that has been proved by culture was reported

in 66 patients from 1996 to 1998 in France, with

incidence 0.04 cases per 100,000 inhabitants per

year. According to published study being held in

USA, annual incidence of this ilness is 0.27

confirmed cases per 100,000 inhabitants.

(Bonamonte et al, 2013) In Asia, fishtank granuloma

incidence is not being reported yet in a large publish

study. However in 2012, Wu TS et al in Taiwan

suceed reporting 27 case finding of Mycobacterium

marinum from 1999 to 2010 in Changung memorial

hospital, while in Indonesia, there are only two case

Nugroho, A., Hidayat, T., Setyowatie, L., Ariaputra, K. and Retnani, D.

Fishtank Granuloma Treated with Combination of Minocycline and Rifampicine.

DOI: 10.5220/0008158203930397

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 393-397

ISBN: 978-989-758-494-7

393

report found from Fauziah SN et al in 2015 and

Barros T et al in 2016 both from RSCM Jakarta,

being treated with combination therapy of

minocycline and rifampicine with good clinical

improvement.(Fauziah et al, 2015,Baros et al, 2015)

Being reported within this case report, one case of

fishtank granuloma in male 40 years old with good

clinical improvement, the lesion healed with scar,

reduction of pain score to zero, after 2 months

therapy with combination rifampicine and

minocycline. Therapy was continued to the third

month to prevent recurrence.

2 CASE

Male, 40 years old came to Outpatient

Departement of Dermatology and Venereology

Saiful Anwar General Hospital with main complain

bumps that ulcerate in his hand since five months

before admission. Initially the bump was solitary,

the size was around 1 cm and look like boils and but

a few weeks, it become bigger, indurated and

painful. The bump was not itch, on a scale 0 out of

10, but it more painful on a scale 6 out of 10. After a

few week occur second bumps next to the first bump

and the bump got ulcerate. This past 3 months, occur

new two bumps closer to the wrist, with the same

characteristic as the previous bumps. No history of

punctured or being manipulated with sharp objects,

woods or branch of a plant. No history being bite by

his pets (patient have turtle and koi fishes as pets).

Patient clean the pond once every twice week and

patient never use gloves when cleaning the pond.

Patient recall that before the occurrence of the bump

that he complains, he has small wounds result from

boils in his wrist that breaks that he ignore

previously. Patient never have any history of chronic

cough more than 3 months. No history of losing

weight since this past years. Throughout the year,

the weight were consistent around 59 kg. After the

occurrence of second bumps, taken to General

Practitioner got zalf contains antibiotic but there not

much improvement. Go to dermatovenereologist, got

Injected with intra lesion corticosteroid but there

was not much changes. On May 2017 the

dermatovenereologist command patient to got

FNAB and culture from the ulcers. Because the

culture show growth of bacteria, the

dermatovenereologist give topical antibiotic therapy.

Not much improvement to the lesion. Patient got

history try to find therapy for his ilness to several

dermatovenereologist and follow the instruction

carefuly of topical therapy but there are no

improvement were achieved. Topical therapy that

patient ever got were nadifloxacine, erythromycine,

metronidazole, sulfur, salycilic acid and

dexpanthenol. Patient never apply traditional herbals

or any other substances to his wounds. Patient is

single. Working as computer technician. Patient got

hobbies of nurturing koi fishes in aquarium, ponds

and have turtles. He clean the fishtank and pond

once a week. No history got bite by his turtle or any

wound appear from his hobbies. But according to the

patient he has history of having boils that breaks and

leave a wound in his wrist and that time, he keep

cleaning the fishtanks anyway with the existing

wound. According to the patient some of his fishes

have ulcer in their body part. Patient clean his yard

twice a month by unplug the wild grasses with bare

hands. He do it to make his garden clean. Patient do

not like gardening or nurturing a specific plant.

Physical examination shows patient compos mentis,

with good general condition.

Figure 1. Clinical improvement after 3 month of

rifampicine 1x600mg and minocycline 2x100mg

Dermatological examination from dorsal manus

dextra, with localized distribution, shows

erythematous nodules, well defined, round to oval,

some confluence, quantity 6, size 0,5 cm – 2 cm,

with ulcer, crust and scales. Zeehl Neelsen stain

examination from the lesion did not show acid fast

bacillus. Blood count examination show

limphocytosis and increase of erythrocyte

sedimentation rate. Chest X-ray within normal

limits, no sign of tuberculosis.

Histopathological examination with HE & PAS

stain shows poorly formed granulation tissues with

no malignancy. Epidermis absent in some part and

acanthosis in the other , while dermis area shows

connective tissue with many blood vessels and

sparse inflammatory cells of neutrophil, lymphocyte

and histiocyte. No visible datia cells and caseous

necrosis. Patient being diagnosed as fishtank

granuloma and being planned for therapy with

rifampicine 1x600 mg and minocycline 2x100 mg

for three months.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

394

3 DISCUSSION

Fishtank granuloma is pathologic condition

causing granulomatous skin and soft tissue lesions in

humans that occur because of Mycobacterium

marinum, aerobic, waterborne atypical

mycobacterium that belongs to Runyon’s

classification Group I photochromogenic non-

tuberculous mycobacteria. This pathogen causing

chronic systemic infections in fish and amphibians,

commonly found in non-chlorinated water

occupying many aquatic environments. In one large

published study by Jernigan et al in 2000, they

observed 193 infections reported from 1962 through

1996 and found that this pathogen were majority

aquarium-related.(Rallis, 2007,Jernigan,

2000,Petrini, 2006 )M. marinum infection occurs

two weeks after direct inoculation of the organism

either from fish fins, bites or from the handling of

aquariums. In 90% of cases, this takes place via

trauma to the upper extremity and do not

transmittable from person to person.(Delphine et al,

2012,Rallis, 2007,Bhatty et al, 2000) In this case

patient got hobby of nurturing koi fishes, and direct

contact with koi fishes and turtle. He also has habit

of cleaning the pond and aquarium without latex

gloves. Patient recall that he has minor lesion few

weeks before the occurrence of the lesion.

Fishtank granuloma begins as a violaceous

papule at the site of a trauma 2-3 weeks after

inoculation. Dermatological examination shows

nodule or psoriasiform or verrucous plaque, usually

occur in hands, feet, elbows or knees.

Infections with

M. marinum can be classified into 4 clinical

categories; Type I (1–3 lesions), Type II: numerous

(> 3) lesions) Type III: deep infections

(tenosynovitis until osteomyelitis), Type IV:

disseminated infection, lung involvement and other

systemic manifestations.(Delphine et al, 2012,Rallis,

2007,Bhatty et al, 2000) Diagnosis is usually

delayed, because most physicians are unfamiliar

with the disease and a failure to establish a history of

exposure to aquatic environments. Therefore, key

diagnostic elements for M. marinum infections are a

high index of suspicion raised by negative bacterial

tissue cultures, poor response to conventional

antibiotic treatments and a history of aquatic

exposure.

Bonamonte et al in 2013, report acid-fast

bacilli identification only can be found in 6.7% case

using Ziehl-Neelsen stain, in accordance with the

low detection rates reported in the international

literature.(Bonamonte et al, 2013) In this patient,

regarding the clinical manifestation, Patient suffer

from fishtank granuloma type II with history of poor

response to various antibiotics and and history of

exposure with aquatic environments. Disseminated

distribution from the lungs can be excluded since

there were no history of chronic cough, or lung

tuberculosis an chest X-Ray of this patient was

normal. The diagnosis of fishtank granuloma was

established based on clinical manifestation and was

then confirmed with histopathological examination

of skin tissues.

Figure 2. Pain score reduce from 6 to 3 on 1st month, completely zero in second month and the third month

There is no standard regimen for therapy of

choice for fishtank granuloma because low

incidence of this infection, and M. marinum is

naturally multi-drug resistant species and treatment

is based primarily on the personal experience and

preference of individual investigators, without any

large studies or randomized controlled trial. In

superficial cutaneous infections, minocycline,

clarithromycin, doxycycline and trimethoprim-

sulfamethoxazole being reported as effective

Before

therapy

1stmonth

2nd

Month

3rdmonth

Painscore

6300

PainScore

Fishtank Granuloma Treated with Combination of Minocycline and Rifampicine

395

monotherapy, but drug resistance varies and thereby

combination therapy using two drugs may be

required.(Rallis, 2007,Doug et al, 2012

)

Like other

atypical mycobacteria, patients suspected of having

atypical mycobacterial skin infections are generally

treated empirically.(Rallis, 2007,Jernigan, 2000)

Minocycline, The second-generation tetracyclines

are the most frequently reported effective treatments.

It inhibits bacterial protein synthesis by preventing

the association of aminoacyl-tRNA with the

bacterial ribosome.(Delphine et al, 2012,Jernigan,

2000)

Cummins et al 2005 describe a case of M.

marinum that improved rapidly with minocycline

despite a lack of response to doxycycline after 6

weeks. Recent in vitro studies with wild-type M.

marinum Strains have shown minocycline to be

more potent than doxycycline. In addition, at least

one minocycline-sensitive strain has shown

resistance to doxycycline.(Cummins et al,

2005,edelstein et al, 1994) Bonamonte et al 2013

collecting 15 case report from 1987 to 2011 and

found 13 cases effectively treat by minocycline 200

mg per day with clinical improvement after 2-3

months.(Bonamonte et al, 2013) Rifampicine in a

dose of 600 mg daily, has been used effectively in

fishtank granuloma either alone or in combination

with other agent. Inhibit RNA synthesis and result in

termination of bacterial replications.(Bonamonte et

al, 2013,Cummins et al, 2005) Speight et al in 1997

has suceed giving rifampicine as single therapy for

fishtank granuloma in 14 month old girl, the patient

got rifampicine as single therapy because

ethambutol and minocycline were contraindicated

due to the patient’s age. In 1994 Elstein et al

collected 31 case report of fishtank granuloma and

conclude that among other treatment, rifampin in

combination with other antimycobacterial appeared

to be more successful and in the next best for fish

tank granuloma therapy is minocycline

treatment.(edelstein et al, 1994,Speight et al,1997)

Duration of therapy that consider effective for

management of atypical mycobacteria is ranging

from four to thirty eight weeks , depends on how the

lesion reponse clinically. It is suggest that the

treatment is continued for next four week after

lesion has resolved to prevent recurrence of illness.

Monotherapy with antimycobacterial agent reported

to be effective but since there are variety in drug

resistency in M. marinum, combination therapy of

usually two drugs were strongly suggested.(Rallis,

2007,Fauziah et al, 2015,Baros et al, 2015) Fauziah

et al in 2016 was reported Mycobacterium marinum

infection that successful being treated with

combination of rifampicine and minocycline, after 2

months.(Fauziah et al, 2015)

4 CONCLUSIONS

Clinical, histopathological feature and clinical

response to minocycline and rifampicine support

establishing diagnosis of fishtank granuloma. There

are clinical improvement, the lesion healed with scar

and reduction of pain score to zero after two months

giving rifampicine 600 mg daily and minocycline

200 mg twice daily, and application of wet gauze

(Na Cl 0,9%) twice daily in this patient. Therapy

were being continued 1 month after resolved of

lesion and pain, to prevent recurrence (Baros et al,

2015) Laboratory examination after release from

treatment shows no elevated liver and renal enzyme,

normal erythrocyte sedimentation rate (ESR) and

other normal laboratory counts. Blue black

discoloration, as side effect of minocycline in the

lesion appear after 3 months therapy but subside

after 1 months release from treatment.

ACKNOWLEDGEMENTS

If any, should be placed before the references

section without numbering.

REFERENCES

Adams, R. M., Remington, J. S., Steinberg, J., & Seibert,

J. S., 1970. Tropical fish aquariums: a source of

Mycobacterium marinum infections resembling

sporotrichosis. JAMA, 211(3), pp. 457-461.

Barros, T., Legiawati, L., Yusharyahya, S. N., Sularsito, S.

A., & Wihadi, I., 2015. Atypical mycobacterial

infection mimicking carbuncle in an elderly patient: A

case report. Journal of General-Procedural

Dermatology & Venereology Indonesia, 32-35.

Bonamonte, D., De Vito, D., Vestita, M., Delvecchio, S.,

Ranieri, L. D., Santantonio, M., & Angelini, G.,2013.

Aquarium-borne Mycobacterium marinum skin

infection. Report of 15 cases and review of the

literature. European Journal of Dermatology, 23(4),

510-516.

Bhatty, M. A., Turner, D. P., & Chamberlain, S. T., 2000.

Mycobacterium marinum hand infection: case reports

and review of literature. British journal of plastic

surgery, 53(2), pp. 161-165.

Cummins, D. L., Delacerda, D., & Tausk, F. A., 2005.

Mycobacterium marinum with different responses to

second-generation tetracyclines. International journal

of dermatology, 44(6), pp. 518-520.

Delphine, J. Lee., Thomas, H. Rea., & Robert, L. Modlin.,

2012. Leprosy. Dalam: Wolff Klaus, Goldsmith

Lowell A, Katz Stephen I, Gilchrest Barbara A, Paller

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

396

Amy S, Leffel David J, penyunting. Fitzpatrick’s

Dermatology in General Medicine. Edisi ke 8. New

York. McGraw-Hill; 2012. h.2253-63 /6.

Dong, D., Wang, D., Li, M., Wang, H., Yu, J., Wang, C.,

... & Gao, Q., 2012. PPE38 modulates the innate

immune response and is required for Mycobacterium

marinum virulence. Infection and immunity, 80(1), pp.

43-54.

Edelstein, H., 1994. Mycobacterium marinum skin

infections: report of 31 cases and review of the

literature. Archives of Internal Medicine, 154(12), pp.

1359-1364.

Fauziah, S. N., Legiawati, L., Sularsito, S. A.,

Yusharyahya, S. N., Rihatmadja, R., Sirait, S. P., ... &

Widyasari, I., 2016. Atypical mycobacterial infection

resembles sporotrichosis in elderly patient. Journal of

General-Procedural Dermatology & Venereology

Indonesia, pp. 62-67.

Jernigan, J. A., & Farr, B. M., 2000. Incubation period and

sources of exposure for cutaneous Mycobacterium

marinum infection: case report and review of the

literature. Clinical infectious diseases, 31(2), pp. 439-

443.

Petrini, B., 2006. Mycobacterium marinum: ubiquitous

agent of waterborne granulomatous skin

infections. European Journal of Clinical Microbiology

and Infectious Diseases, 25(10),pp. 609-613.

Rallis, E., 2007. Koumantaki-Mathioudaki E. Treatment

of Mycobacterium marinum cutaneous infections.

Expert Opin Pharmacother 8, pp. 2965-2978.

Speight, E. L., & Williams, H. C., 1997. Fish Tank

Granuloma in a 14-Month-Old Girl. Pediatric

dermatology, 14(3), pp. 209-212.

Wu, T. S., Chiu, C. H., Yang, C. H., Leu, H. S., Huang, C.

T., Chen, Y. C., ... & Chia, J. H., 2012. Fish tank

granuloma caused by Mycobacterium marinum. PloS

one, 7(7), e41296.

Fishtank Granuloma Treated with Combination of Minocycline and Rifampicine

397