Lymphoscintigraphic analysis in chromoblastomycosis

Report Blackwell Oxford, 0011-9059 41 International IJD UK Publishing Science, Journal 2002 Ltd. of Dermatology Lymphoscintigraphic analysis in chromoblastomycosis XXXX Ogawa et al. Marília M. Ogawa, MD, Maurício M. A. Alchorne, MD, Antonio Barbieri, MD, Mário L. V. Castiglioni, MD, Adriana Porto Benatti Penna, MD, and Jane Tomimori-Yamashita, MD From the Departments of Dermatology and Nuclear Medicine, Federal University of São Paulo, Brazil Correspondence Jane Tomimori-Yamashita, MD, Department of Dermatology, UNIFESP-EPM, Rua Botucatu 740, 04023 –900, São Paulo, SP, Brazil. E-mail: [email protected] 622 Abstract Background One of the main complications of chromoblastomycosis is lymphedema. The purpose of this study was to evaluate the lymphatic system of the limbs of patients with chromoblastomycosis using lymphoscintigraphy. It is a reliable, objective and noninvasive means of supporting the diagnosis of lymphedema. Methods Lymphoscintigraphy was performed in seven patients with chromoblastomycosis, six with lesions in the lower limb and one in the upper limb. Tc-99 m dextran was injected into the interdigital spaces of the upper or lower extremities. The qualitative parameters analyzed were the visibilization of the lymph vessels and the lymph nodes, dermal backflow, and existence of collateral vessels. All patients were treated with the association of itraconazole and cryotherapy with liquid nitrogen. Results Three out of the 14 extremities examined had lymphedema clinically, and the lymphoscintigraphy showed abnormalities in the qualitative parameters; whereas these parameters were normal in the extremities without lymphedema. During the treatment of chromoblastomycosis, a second lymphoscintigraphy exam was performed on 10 limbs and did not show any improvement of the previous lymphoscintigraphic alterations. Conclusions The qualitative lymphoscintigraphy was a reliable method to show the morphology of the lymph vessels and confirm objectively the diagnosis of lymphedema secondary to chromoblastomycosis. The association of oral itraconazol and cryotherapy did not modify the lymphatic alterations in chromoblastomycosis. Introduction Materials and Methods Chromoblastomycosis is a chronic fungal infection that affects mainly the skin and subcutaneous tissues. It is caused by several species of dematiaceous or pigmented fungi. The infection generally occurs in individuals residing in rural areas from tropical and subtropical countries. The primary lesion begins as a papule that gradually enlarges to a verrucose plaque. It may spread progressively, and in advanced cases extensive fibrosis often blocks the lymphatics causing lymphostasis, which facilitates secondary infections.1 These recurrent bacterial infections lead to gross lymphedema, which may disable the patient. The purpose of this work was to assess the lymphatic qualitative alterations caused by this disease using lymphoscintigraphy, as it is a reliable, objective and non invasive test,2 as well as to study whether the treatment of chromoblastomycosis with itraconazol and cryotherapy is capable of improving lymphoscintigraphy qualitative alterations secondary to this disease. Subjects Seven patients (five men and two women) aged 28–73 years were evaluated by lymphoscintigraphy. The duration of the disease varied from 10 years to 47 years. All patients had unilateral lesions: six on the lower limb and one on the upper limb. Histopathology exam and culture on the Sabouraud’s medium confirmed the diagnosis of chromoblastomycosis. The patients were treated with association of oral itraconazol (200 – 400 mg daily) and cryotherapy with liquid nitrogen. International Journal of Dermatology 2003, 42, 622 – 625 Clinical classification of lymphedema The clinical classification of lymphedema was based on the classification suggested by Miller et al.,3 who used the concepts of inspection, palpation, gravitational effects and extremities function: 1 Grade I: normal appearance; edema pits on pressure; edema disappears or decreases markedly with limb elevation; and normal limb function. © 2003 The International Society of Dermatology Ogawa et al. Chromoblastomycosis and lymphoscintigraphy Report 2 Grade II: yellowish appearance; early skin thickening, and little pitting on pressure; edema decreases moderately with limb elevation; and limb mobility decreased. 3 Grade III: lichenification and early keratotic changes on the limb inspection; skin thickening, and little pitting on pressure; edema decreases minimally with limb elevation; marked functional loss, impairment of fine movements, and loss of joint flexibility. 4 Grade IV: yellowish discoloration increases, increased pigmentation, weeping vesicles, keratotic papules and lichenification on the limb inspection; thickening of skin and no pitting on pressure; edema does not decrease with limb elevation; marked functional loss, and movements are markedly impaired. Image procedure Lymphoscintigraphy was performed with gamma camera APEX SPX-4 H- Elscint ®. The technique involved the intradermic injection of Tc-99 m dextran into the first interdigital space of the upper or lower extremities in a total dose of 185 MBq. Static anterior images were obtained in all patients within the first hour and 3 h after injection at the injection sites, distal and proximal extremities, and regional lymph nodes. In five patients, the lymphoscintigraphy was repeated after a period of treatment that varied from 6 months to 4 years. Appropriate informed consent was obtained from all subjects. Image interpretations The following patterns were considered an abnormal lymphoscintigraphy image:2 1 No removal of activity from the injection site; 2 Delayed transport from the injection site; 3 Dermal backflow consistent with interstitial dermal lymph transport; 4 Nonvisibilization of lymphatic channels on the involved side and nonvisibilization or faintly visibilized lymph nodes; and 5 Crossover filling of major nodes caused by proximal obstruction and collateral circulation. Results By clinical examination, two out of seven extremities affected by chromoblastomycosis presented lymphedema grade III (observations 1 and 2) and one presented lymphedema grade IV (observation 5). In the other four extremities the lymphedema was not observed. The distribution of chromoblastomycosis lesions, the grade of lymphedema, and the lymphoscintigrapic pattern of the affected limb is shown in Table 1. The lymphoscintigraphic patterns were abnormal in all extremities with clinical lymphedema (observations 1, 2, and 5). On the extremities without chromoblastomycosis lesions and on the extremities with chromoblastomycosis lesions but without lymphedema the lymphoscintigraphy was normal. In the extremity with lymphedema grade IV (observation 5), the radionuclide was retained at the injection site (Fig. 1) without visibilization of the lymphatic channels and lymph nodes. On the other two extremities with lymphedema grade III (observations 1 and 2) the lymphoscintigraphic patterns showed delayed transport of the radionuclide, dermal backflow, faintly visibilized lymph nodes compared with the normal extremities, and collateral circulation (Fig. 2). The five patients who were submitted for a second lymphoscintigraphy study (observations 1, 2, 3, 5, and 7) did not show any change in the image pattern, except in one patient (observation 2) who interrupted the treatment for 9 months. Clinically this patient had a worsening of the lymphedema, which was accompanied by a change in the lymphoscintigraphic pattern such as a decrease in the visibilization of the lymphatic vessels and in the amount of radionuclide in the lymph nodes. Discussion An important complication of the chromoblastomycosis on the lower or upper limbs is lymphedema. Cucé et al.4 observed this complication in 22 patients out of 37 patients with chromoblastomycosis. The factors involved in the Table 1 Distribution of the chromoblastomycosis lesions, the grade of clinical lymphedema of the affected extremity (classification proposed by Miller et al.3) and the respective lymphatic pattern in lymphoscintigraphy (lymphatic flow, retention of the radionuclide, dermal backflow, and the concentration of the radionuclide in the lymph nodes) Patient Localization of lesions Clinical lymphedema Lymphatic flow Retention of the radionuclide Dermal backflow Lymph node 1 2 3 4 5 6 7 Left ankle and foot Left foot Right buttock and thigh Right thigh and knee Right lower limb Right foot Right elbow Grade III Grade III Absent Absent Grade IV Absent Absent Retarded Retarded Normal Normal Absent Normal Normal Present (below the knee) Present (below the knee) Absent Absent Present (injection site) Absent Absent Present Present Absent Absent Absent Absent Absent Normal Low concentration Normal Normal Absent Normal Normal © 2003 The International Society of Dermatology International Journal of Dermatology 2003, 42, 622 – 625 623 624 Report Chromoblastomycosis and lymphoscintigraphy Figure 1 One-hour (on the left) and 3-h (on the right) images show a complete obstruction of the lymphatic system on the right lower extremity represented by retention of the radionuclide at the injection site and no visibilization of the lymphatic vessel. This patient had lymphedema grade IV (observation 5) Figure 2 One-hour (on the left) and 3-h (on the right) images show dermal backflow, faint visibilization of lymph nodes compared with the normal extremity and ascension of the radionuclide through the deep collateral circulation on the left lower extremity, suggesting a secondary lymphedema. This patient had lymphedema grade III (observation 2) development of the lymphedema could be: (1) that intensive fibrosis can block the lymphatics, causing lymphostasis and consequently lymphedema of the limb, in advanced cases;1 and (2) recurrent secondary infections.5 Lymphedema by International Journal of Dermatology 2003, 42, 622 – 625 Ogawa et al. itself predisposes to limb infections, causing a worsening of the lymphedema. Cryotherapy, used as a treatment for chromoblastomycosis, could facilitate a secondary infection of the ulcer caused by the application of liquid nitrogen. Lymphedema has an important impact on the patient’s life, and in the literature there is no study showing lymphatic system abnormalities in this disease. Lymphoscintigraphy is the procedure used to evaluate the lymphatic malfunction and is effective in the characterization of lymphatic morphology.2,6 The evidence of lymphedema by lymphoscintigraphy is usually based on the transport or delayed transport of activity, dermal backflow, nonvisibilization, or faintly visible lymph nodes on the involved extremities and collateral lymph vessels.2 This study showed that all extremities with clinical lymphedema presented these lymphoscintigraphy abnormal findings according to the grade of the lymphedema. On the other hand, the limbs affected by chromoblastomycosis but without lymphedema had a normal lymphoscintigraphy. However, Cestari7 who examined the lymphatic system of 24 lower extremities using this method, observed that five out of seven limbs without any clinical evidence of lymphedema had an abnormal lymphoscintigraphic pattern, which may have resulted from congenital abnormalities of the lymphatic system. In this study there was no correlation between the extension of the chromoblastomycosis lesions and the grade of the lymphedema, as both patients who presented grade III lymphedema had localized chromoblastomycosis lesions. In one case (observation 1) the lesions affected the dorsal of the foot, whereas in another patient (observation 2) the distal part of the dorsal of the foot and ankle were affected. Witte,8 studying the lymphatic abnormalities in Kaposi sarcoma, associated observed focal accumulation within lymphatic channels in the distribution of cutaneous Kaposi sarcoma lesions with AIDS. In this study, we also looked for a correlation between chromoblastomycosis lesions and a specific lymphoscintigraphic pattern, however, this correlation was not observed in chromoblastomycosis. Among parasitic infections, lymphoscintigraphy is greatly used to assess lymphatic abnormalities resulting from bancroftian filariasis, which damages the lymphatic system. Moore et al.9 suggested the use of lymphoscintigraphy in identifying individuals with acute lymphatic filariasis, as he reported the reversal of both physical and lymphoscintigraphic abnormalities in a patient with acute bancroftian filariasis treated with diethylcarbamazine. However, in the patients with chronic filarial infections with irreversible lymphatic damage, the specific treatment with diethylcarbamazina did not improve the lymphatic dysfunction.10 In our study, the improvement of the chromoblastomycosis lesions as a result of the treatment with itraconazole and cryotherapy with liquid nitrogen was not accompanied by improvement of either the clinical lymphedema or the © 2003 The International Society of Dermatology Ogawa et al. lymphoscintigraphic abnormalities. Cryotherapy using liquid nitrogen causes blisters and ulcers that can facilitate secondary infections, consequently worsening the lymphedema. In conclusion, lymphoscintigraphy has been proven to be an important tool in assessing more precisely the abnormalities of the lymphatic system in chromoblastomycosis patients, though we did not observe any lymphoscintigraphy abnormality specific for this disease. This study also demonstrated that specific treatment of chromoblastomycosis did not modify the course of lymphedema. Moreover, the lymphedema was not related to the extension of this cutaneous mycosis. References 1 McGinnis MR. Chromoblastomycosis and phaeohyphomycosis. New concepts, diagnosis, and mycology. J Am Acad Dermatol 1983; 8: 1 – 16. 2 Ter S-E, Alavi A, Kim CK. Lymphoscintigraphy: a reliable test for the diagnosis of lymphedema. Clin Nucl Med 1993; 18: 646 – 654. 3 Miller AJ, Bruna J, Beninson J. A universally applicable clinical classification of lymphedema. Angiology 1999; 50: 189 – 192. © 2003 The International Society of Dermatology Chromoblastomycosis and lymphoscintigraphy Report 4 Cucé LC, Salebian A, Gatti CF, Sampaio SAP. Cromomicosis. Estudio de 37 casos. Revista Argentina Dermatológica 1983; 64: 1 – 5. 5 Vollum DI. Chromomycosis: a review. Br J Dermatol 1977; 96: 454 – 458. 6 Weissleder H, Weisslede R. Lymphedema: Evaluation of qualitative and quantitative lymphoscintigraphy in 238 patients. Radilogy 1988; 167: 729 – 735. 7 Cestari SCP, Petri V, Castiglioni MLV, Lederman H. Linfedemas dos membros inferiores: estudo linfocintilográfico. Revista Associação Médica Brasileira 1994; 40: 93 –100. 8 Witte MH, Fiala M, McNeill GC, et al. J. Lymphangioscintigraphy in AIDS-associated Kaposi Sarcoma. Am J Radiol 1990; 155: 311 – 315. 9 Moore TA, Reynolds JC, Kenney RT, et al. Diethylcarbamazine-induced reversal of early lymphatic dysfunction in a patient with bancroftian filariasis: Assessment with use of lymphoscintigraphy. Clin Infectious Dis 1996; 23: 1007 – 1011. 10 Freedman DO, Bui T, Almeida Filho PJ, et al. Lymphoscintigraphic assessment of the effect of dietylcarbamazine treatment on lymphatic damage in human bancroftian filariasis. Am J Trop Med Hygiene 1995; 52: 258 – 261. International Journal of Dermatology 2003, 42, 622 – 625 625