Heat Therapy as an Excellent Adjuvant Treatment for Severe

Chromoblastomycosis: A Case Report

Lusiana, Rizky L. Prayogo, Rahadi Rihatmadja, Sandra Widaty, Sri Linuwih Menaldi, Eliza

Miranda.

Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia / Dr. Cipto Mangunkusumo

General Hospital, Jakarta Indonesia.

Keywords: chromoblastomycosis, heat therapy, itraconazole.

Abstract: Chromoblastomycosis is a subcutaneous infection commonly found in tropical and subtropical areas, caused

by dark-pigmented fungi (Dematiaceae). The disease is most frequently observed in extremities with

previous history of trauma and is associated with agricultural occupation. It is characterized by a clinical

presentation of verrucous nodule or plaque, muriform bodies on direct smear and histopathological

examination and slow growing, black-brown colony on the culture. It has been reported that several

treatment options for chromoblastomycosis are studied with varied cure rate, both physical therapy and

systemic antifungal drugs. Heat therapy was a method that applies heat to the lesion thereby inhibit the

growth of fungi. Here we report a severe chromoblastomycosis case which had combination treatment of

heat therapy and itraconazole and showed favourable outcome.

1 INTRODUCTION

Chromoblastomycosis (CBM) commonly occur in

tropical and subtropical regions, and it is caused by

Dematiaceae such as Fonsecaea pedrosoi,

Phialophora verrucosa and Cladophialophora

carrionii as the most common pathogen species.

(Hay, 2012,Queiroz, 2017) Dematiaceae refers to

fungi containing melanin in their cell walls

microscopically visible by a gross brown,

olivaceous, or black pigmentation. (Queiroz, 2017)

Fungi inoculation exist because of direct

transcutaneous implantation in the lower extremity

as the predilected area, followed by upper extremity

and upper part of the trunk with the history of

trauma and associated with particular occupation in

the farm land or in the agricultural field. (Queiroz,

2015)

The initial lesion may begin with erythematous

macular or squamous papule, and then it may

gradually extended within months or years and

eventually become polymorphic, hyperkeratotic

papules-nodules, cauliflower-like or verrucous

plaques with atrophic scar in the middle part. (Hay,

2012,Queiroz, 2017,Agarwal, 2017,Purim, 2017)

Diagnosis is established based on medical history,

physical examination and identified Dematiceae.

The presence of muriform or sclerotic bodies by

direct examination with potassium hydroxide (KOH)

and histopathological examination and also on the

culture we can find slow-growing, black-brown

colonies with soft hairy surface.

It has been reported that there are several

therapeutic options for CBM, such as physical

therapeutic methods (heat therapy, excisional

surgery, electrosurgery, CO2 laser, heat therapy, and

photodynamic therapy) and systemic antifungal

agent. (Queiroz, 2017,Hiruma, 1993-Hira, 2002)

According to several open and noncomparative

clinical trials, itraconazole is the standard therapy

for CBM, and it is also the most common antifungal

drug used that can be combined with other

modalities. The recovery rate varies, however in the

chronic case and severe lesion it is common to get

insufficient outcome with high rate of disease

reccurence. Heat therapy is a potential therapeutic

option for CBM that is easy to use with good

response. Several complications that is commonly

encountered in CBM are secondary bacterial

infection that may cause lymphatic fibrosis and

extremity elephantiasis. Chronic diseases may also

developed to become squamous cell carcinoma.

(Hira, 2002)

406

Lusiana, ., Prayogo, R., Rihatmadja, R., Widaty, S., Menaldi, S. and Miranda, E.

Heat Therapy as an Excellent Adjuvant Treatment for Severe Chromoblastomycosis: A Case Report.

DOI: 10.5220/0008158504060410

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 406-410

ISBN: 978-989-758-494-7

2 CASE

A 50-year-old male visited the Dermatology and

Venerology Outpatient Clinic at the Dr. Cipto

Mangunkusumo General Hospital on 7 September

2017 with chief complaint of cauliﬂower-like

masses with black spots that has spread to the right

lower extremity since 10 years ago. Initially, the

middle finger of the right feet was hurt by knife, and

then red spot appear in the dorsal pedis, above the

wound surface and extended gradually, become

hyperkeratotic papules-nodules, cauliflower-like or

verrucous plaques with atrophic scars in the middle

part. The lump was itch and painful especially after

activities, sometimes bleeding if it is scratched or

traumatized. The patient had several medical

consultations at the Community Health Centre

where he received antihistamine, pain killer, and

topical therapy. However, the symptoms did not

improved. The patient frequently worked at the farm

land, taking care of crops without any foot cover.

Previous history of malignancy, lung disease or

chronic cough in the patients and family were

denied.

On physical examination, the general condition

and vital signs were within normal limit. On the

right lower extremity and ventral side of the right

foot, there were multiple erythematous and skin-

colored papules, nodules, vegetative plaques with

black spots. There were hypertrophic scars between

these lesions (Fig.2a). There was no enlargement in

the lymph node. The direct examination with KOH

showed some muriform cells or sclerotic bodies.

Histopathological examination revealed

hyperplasia pseudoepitheliomatosa appearance, and

in the dermis there were lymphocyte cells

infiltration, histiocytes, plasma cells and

multinucleated and Langhans giant cells. There were

muriform cells with thick wall and brown-coloured

in the cytoplasm of giant cell (Fig.1a). Tissue culture

on Sabouraud's dextrose agar (SDA) medium grown

slow-growing, dark-brown colonies, with slightly

elevated center (Fig.1b). Microscopic examination

with lactophenol cotton blue (LPCB) staining

revealed brown conidiophores, ovoid conidia that

located at the end or at the side of conidiophores

concluded as Foncecaeae pedrosoi (Fig.1c).

All of these examination results supported the

diagnosis of CBM. Patient was given itraconazole

200 mg daily combined with heat therapy. As the

heat therapy, patient used hot water rubber pocket

with temperature around 50–60

C for 30-60 seconds,

3 times daily (Fig.1c). Clinical improvement has

been observed within 1 month of therapy. Visually,

the swelling became smaller, black granules were

disappeared, the pain and itch symptoms were

vanished. During 4 months of follow up, most of the

swelling was thinner (Fig.2b). Nodular type lesion

was faster to become small compared to plaque-

shaped lesions and hypertrophic scars. The liver and

kidney functions was routinely examined every

month.

Figure 1. a. Muriform cells, b. Colony of F. pedrosoi

(macroscopic), c. Slide culture of F. pedrosoi

(microscopic, LPCB), d-e. Heat therapy procedure.

3 DISCUSSION

Chromoblastomycosis is more common in

male, with male-to-female ratio of 4:1, and

predominantly between 30-50 years of age

because risk of trauma was higher in these

groups of population. (Santos,2007) Disease

transmission was due to inoculation of non-

intact skin with fungi Dematiceae from soil or

contaminated crops. The patient was a 50-year-

old male, works at farm and seldomly use foot

protector. Patient had a history of cutting

wound on his foot 10 years ago. Several months

later there were red spots on the surface above

the cut wound. From the medical history, the

patient demographic status was consistent with

epidemiology characteristic of CBM, such as

gender, age, and occupation type. (Santos,

2007) History of trauma surrounding the lesion,

history of occupation, and infrequent use of

foot protector, were the risk factors that may

create a port d’entrée for the fungi and

eventually resulted in subcutaneous mycosis

infection. (Santos, 2007)

Heat Therapy as an Excellent Adjuvant Treatment for Severe Chromoblastomycosis: A Case Report

407

Figure 2. a. Before treatment, cauliflower-like lesions, b. After 4 month combination therapy, the lesions smaller, thinner,

black spots dissapear.

Diagnostic techniques of CBM are based on

physical and direct examination, culture and

histopathology.Queiroz,2009 From direct scrap of

KOH and skin biopsy in the lesion surface

containing black spots, we could find the disease

hallmark of CBM or pathognomonic fungi structure:

muriform cell or sclerotic bodies or fumagoid cells

or copper pennies.(Queiroz, 2017;Queiroz, 2015;

Queiroz,2009) Muriform cells had thick wall like

chestnut, round-shaped, brown color with cross

chamber, tranversal and longitudinal, and this is as

result of fungi adaptation in order to survive in the

host tissue. (Queiroz, 2017; Queiroz, 2015) The

sensitivity of direct examination with KOH for CBM

was 90-100%. (Queiroz, 2017) Therapy may be

started upon the demonstration of muriform cells,

however, culture identiﬁcation is important because

Fonsecaea species may be less sensitive to

antifungals. (Queiroz, 2017) From all the signs,

symptoms and examinations results in this patient

we concluded the diagnosis was CBM and

categorized as severe degree based on the lesion size

of more than 15 cm2.13

Therapy of CBM consists of several modalities,

such as systemic antifungal medication, physical

therapy, surgical or combination of these modalities.

(Queiroz, 2017; Hiruma,1993) Options and outcome

of treatment were dependent by the etiological

pathogen, size of lesion, and the degree of the

disease, complication, like dermis fibrosis and

edema that can reduce the drug concentration in the

tissue. The most effective systemic antifungal drugs

is itraconazole (200-400 mg/day) or terbinafine

(500-1000 mg/day) minimally 6-2 months therapy.

In the refractory cases, both drugs could be given

simultaneously. F. pedrosoi was said to be

insensitive to systemic antifungal drugs compared to

C. carrionii and P. verrucosa and there was a report

of resistance to itraconazole. (Hira, 2002, Andrade,

2004) In this case, itraconazole was still sensitive

with rapid clinical improvement. Heat therapy was a

method that applies heat so that the lesion

temperature reach 42-45oC. (Queiroz, 2015)The

mechanism of action relies on fungal intolerance to

high temperature. (Queiroz, 2017) Yanase et al.

reported that maximal temperature of F. pedrosoi for

growth was 390C.(Yanase, 1978) Heat therapy has

particularly been applied in Japan, with several

methods. Application of a chemical pocket warmer

occluded with a bandage over the lesions on 24 h per



2a

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

408

day, or local heat therapy for 2 h perday combined

with the administration of posaconazole, or

combination of heat therapy for 12 h perday and

terbinaﬁn, resulted in an improvement of lesions and

negative microscopic examination and culture

results within 2-8 months. (Queiroz, 2017; Yanase,

1978)

In this case the combination of itraconazole 200

mg/day with heat therapy, using rubber pocket water

warmer, about 50-600C for only 30-60 minutes,

showed good response within one month, as it was

faster than previous reports. During evaluation after

four months of treatment, the response was

excellent, the swelling became smaller and thinner,

and the surface became smoother. The itch and pain

were vanished. Itraconazole is planned to be given

for 12 months with monthly follow up.

Treatment of CBM needs to be monitored and

evaluated clinically, mycologicaly,

hystopathologically every three or four months.

(Queiroz, 2017) The disease can be assessed as

clinically cured if the lesion resolution was obtained

completely, with sclerotic scar without subjective

symptoms such as pain or pruritus. (Queiroz,

2017,Hira, 2002) Mycological cure is defined by the

negative results of direct microscopic and culture.

(Queiroz, 2017) In this case direct examinations

with KOH showed negative result during four

months therapy. Histopathological cure is achieved

if there are no muriform cells, microabscesses and

granulomas, and are being replaced by the

appearance of chronic inactive inflammation and

fibrosis. (Queiroz, 2017) The variable cure rate of

CBM is 15%–80% depending on the severity of the

disease, and it will increase when two or more

modalities were used in combination. (Queiroz,

2015,Agarwal, 2017)

4 CONCLUSION

There is a risk of treatment failure and

recurrence in CBM. In a patient with severe and

extended lesion, the aim of treatment are to

reduce the lesion size and control the state of

the disease so that there will be no complication

and to improve patient quality of life.

Hira, 2002

Heat therapy is a potential therapeutic option

for CBM that is easy to use, affordable prices,

and combination with itraconazole showed

good clinical response in this case.

REFERENCES

Agarwal, R., Singh, G., Ghosh, A., Verma, K. K., Pandey,

M., & Xess, I., 2017. Chromoblastomycosis in India:

review of 169 cases. PLoS neglected tropical

diseases, 11(8), 1-13, e0005534.

Andrade, T. S., Castro, L. G., Nunes, R. S., Gimenes, V.

M., & Cury, A. E., 2004. Susceptibility of sequential

Fonsecaea pedrosoi isolates from

chromoblastomycosis patients to antifungal

agents. Mycoses, 47(5‐6), pp. 216-221.

Ameen, M., 2009. Chromoblastomycosis: clinical

presentation and management. Clinical and

Experimental Dermatology: Clinical

dermatology, 34(8), pp. 849-854.

Hay R.J., 2012. Deep fungal infections. In: Goldsmith

LA, Katz SI, Gilchrest BA, Paller AS, Leffel JD,

Wolff K, editor. Fitzpatrick’s dermatology in general

medicine. 8

Edition. New York: McGraw-Hill, 2312-

2317.

Hira, K., Yamada, H., Takahashi, Y., & Ogawa, H., 2002.

Successful treatment of chromomycosis using carbon

dioxide laser associated with topical heat

applications. Journal of the European Academy of

Dermatology and Venereology, 16(3), pp. 273-275.

Hiruma, M., Kawada, A., Yoshida, M., & Kouya, M.,

1993. Hyperthermic treatment of chromomycosis with

disposable chemical pocket

warmers. Mycopathologia, pp. 122(2), 107-114.

Hu, Y., Huang, X., Lu, S., Hamblin, M. R., Mylonakis, E.,

Zhang, J., & Xi, L., 2015. Photodynamic therapy

combined with terbinafine against

chromoblastomycosis and the effect of PDT on

Fonsecaea monophora in

vitro. Mycopathologia, 179(1-2),pp. 103-109.

Purim, K. S. M., Peretti, M. C., Fillus Neto, J., &

Olandoski, M., 2017. Chromoblastomycosis: tissue

modifications during itraconazole treatment. Anais

Brasileiros de Dermatologia, 92(4), pp. 478-483.

Queiroz-Telles, F., Esterre, P., Perez-Blanco, M., Vitale,

R. G., Salgado, C. G., & Bonifaz, A., 2009.

Chromoblastomycosis: an overview of clinical

manifestations, diagnosis and treatment. Medical

mycology, 47(1), pp. 3-15.

Queiroz-Telles, F., 2015. Chromoblastomycosis: a

neglected tropical disease. Revista do Instituto de

Medicina Tropical de São Paulo, 57, 46-50.

Queiroz-Telles, F., de Hoog, S., Santos, D. W. C.,

Salgado, C. G., Vicente, V. A., Bonifaz, A., ... & Pana,

Z. D., 2017. Chromoblastomycosis. Clinical

microbiology reviews, 30(1), pp. 233-276.

Santos, A. L., Palmeira, V. F., Rozental, S., Kneipp, L. F.,

Nimrichter, L., Alviano, D. S., ... & Alviano, C. S.,

2007. Biology and pathogenesis of Fonsecaea

pedrosoi, the major etiologic agent of

chromoblastomycosis. FEMS microbiology

reviews, 31(5), pp. 570-591.

Shantala, G.B., Rudresh, S.M., Nagarathnamma, T, 2011.

Chromoblastomycosis: A Case Report. JCDR, 5(4),

pp. 864-866.

Heat Therapy as an Excellent Adjuvant Treatment for Severe Chromoblastomycosis: A Case Report

409

Yanase, K., & Yamada, M., 1978.. Pocket-warmer'therapy

of chromomycosis. Archives of dermatology, 114(7),

pp.1095-1095.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

410