INTRODUCTION
The first report of Lobo’s disease, called lobomycosis or currently known as
lacaziosis, was first described in 1930 by a Brazilian dermatologist, Jorge
Lobo.
The majority of the cases described in humans, approximately 500 cases worldwide,
is restricted to jungle regions, with hot and humid climate, abundant water
courses, and high rainfall, such as the Brazilian Amazon region.
Approximately 300 cases were registered in Brazil; lacaziosis cases have also
been reported in Peru, Colombia, Venezuela, French Guiana, Guyana, Bolivia,
Ecuador and Suriname, with approximately 200 registered cases registered1; rare cases have also been described in
other parts of the world, such as North America2,3, Central
America and some European 4,5 and African
countries6.
The etiologic agent is the saprophytic fungus, Lacazia loboi,
which is present in water, soil and vegetation. The mode of transmission is not
known, and infection may be transmitted by inoculation of the fungus by
solutions of continuity of skin; this is often caused by trauma with plant
fragments and insect stings7,8.
History and pathogenesis
The parasite, Lacazia loboi, over time, has been designated
in different ways, with the current nomenclature being adopted in 1999 by
Taborda et al.7. The term
lacazia comes from the name of the Brazilian
mycologist, Carlos da Silva Lacaz, who greatly contributed to a better
understanding of this disease, and the term loboi was
adopted to honor the first physician to describe the disease, Jorge
Lobo.
In 2007, Hibbett et al.8 classified the
fungus as belonging to the phylum Ascomycota, subphylum Pezizomycotina,
class Eurotiomycetes, subclass Eurotiomycetidae, order Onygenales, and
family Onygenceae.
Its phylogenetic classification was based on the identification of the fungus
using the 18s ribosomal subunit DNA and a 600-bp fragment of the CHS2 gene
(chitin synthetase 2) from yeast cells 9,10.
In addition to humans, two species of dolphin, Tursiops
truncates11
and Sotalia guianensis12.13, are
affected by this parasite.No cases of lacaziosis in harbor porpoises or
dolphins in the area of the Amazon basin have been described.
The individuals most affected are laborers in the aforementioned areas, with
most of them being rubber tappers, lumberjacks, farmers, fishermen, and
miners of precious stones7,8; these
individuals are usually males aged around 50 years14.
Little is known about the mode of transmission of the disease; the only known
way is the inoculation of the parasite from cells infected with the fungus.
Inter-human transmissions have never been described. There is only one
report of transmission to humans in the literature, wherein the infection
was transmitted by a piercing and blunt accident with material infected with
the parasite15,16; however, transmission may occur
when there is contamination in areas of the skin with loss of continuity
(wounds) and lobomycosis lesions11.
Once in contact with the dermis, the fungus is phagocytosed and slow
proliferation of the parasite is then initiated. Dissemination may occur
through local lymphatic continuity via the regional and hematogenic
ganglia7,16,17. There is no information regarding the incubation
period or latency of this disease; however, elimination or treatment of this
infection is difficult due to the high resistance of the parasite, with
disease recurrence being very frequent. There are reports of individuals
infected by dolphins, with the latency periods varying from 3 months to 4
years18-20.
There is only one case report of lacaziosis11. The immunological response of the skin to the parasite is
still not clearly understood. From a histological viewpoint, the lesions are
characterized by little organized granulomas composed of histiocytes (CD68),
Langerhans cells, and multinucleated giant cells. Immunohistochemical
studies revealed the presence of a small number of the following mononuclear
cells: T lymphocytes (CD3+), helper T lymphocytes (CD4+), cytotoxic T
lymphocytes (CD8+), B lymphocytes (CD20+), plasmocytes (CD79+), and NK cells
(CD57+)19. Vilani-Moreno et
al.21 suggested that fungi are
phagocytosed by histiocytes, which give rise to the giant Langerhans cells;
thus, the typical granulomas observed in this disease are formed.
Langerhans cells are responsible for the presentation of antigens in numerous
infections. To better understand the disease, Quaresma et al.18 performed an immunohistochemical
study of Langerhans cells and verified that although there are no
morphological changes with respect to normal cells, there is an escape
mechanism for the presentation of these antigens by Langerhans cells21.
The is no association between lobomycosis and specific antigens of the class
II HLA system; however, the decrease in the frequency of HLA-DR7 antigen in
the patient group compared to the control group indicates a protective
relationship of HLA-DR7 with lobomycosis.
Clinical Presentation
The lesions of lobomycosis usually appear in exposed areas and in response to
trauma; the lesions are frequently observed in the ears, upper and lower
limbs, face, chest, and cervical region, and especially in areas with low
temperature.
The clinical diagnosis of lobomycosis is usually delayed, since the patients
seek medical service due to a nodular lesion in the subcutaneous tissue that
is slightly pruriginous and painless and grows slowly and steadily over the
years.
Brito & Quaresma6 classified the
lesions of lobomycosis as monomorphic and polymorphic (macules, papules,
nodules, gums, nodular plaques, verruciform lesions, scarring, and aphthous
lesions), with a predominance of nodular lesions.
More recently Opromolla et al.20,
ranked them as: i) isolated form (Figure 1); (ii) disseminated form (Figure 2); and (iii) multifocal form (Figure 3), that is, multiple localized lesions in just one limb
or limb segment. There are other descriptions based on the morphological
appearance of the lesions, such as descriptions provided by Lacaz14, Dias et al.22, and Ramos and Silva23, which are as follows: infiltrative, keloidal, plaque,
verruciform, and ulcerated (Figures 4-6, respectively). Another
lacaziosis classification system was suggested by Lacaz24 et al., who described it as isolated form,
disseminated form, and multifocal (Figures 4, 5, and 6, respectively). The existing
classifications often differ only in the description of the lesions
(author’s note).
Figure 1 - Infiltrative form: A patient with a lesion in the left ear
that progressed during a disease course of 23 years. Note a
satellite lesion below the ear.
Figure 1 - Infiltrative form: A patient with a lesion in the left ear
that progressed during a disease course of 23 years. Note a
satellite lesion below the ear.
Figure 2 - Keloid form: A patient with a lobomycosis lesion in the right
breast that progressed during a disease course of 20
years.
Figure 2 - Keloid form: A patient with a lobomycosis lesion in the right
breast that progressed during a disease course of 20
years.
Figure 4 - Isolated form: A single lesion in the right ear that
progressed during a disease course of 2.8 years..
Figure 4 - Isolated form: A single lesion in the right ear that
progressed during a disease course of 2.8 years..
Figure 5 - Disseminated form: A patient with lesions affecting the whole
lower limb.
Figure 5 - Disseminated form: A patient with lesions affecting the whole
lower limb.
Figure 6 - Multifocal form: Multiple foci of lesions in the forearm,
elbow, and arm.
Figure 6 - Multifocal form: Multiple foci of lesions in the forearm,
elbow, and arm.
Diagnosis
The diagnosis can be established by mycological examination,
histopathological assessment, and immunohistochemical staining. To date, the
culture of this parasite has not been obtained13. In our service, the mycological examination is
conducted initially through puncture of the nodules, aspiration of the
contents, and direct observation of the parasite on a slide. The
anatomopathological examination is performed with hematoxylin-eosin
staining, as proposed by Vilela et al.10. Fungi can also be visualized by fresh Grocott-Gomori
staining or with calcofluor and Periodic acid–Schiff (PAS) staining7.
Staining with ethidium bromide revealed that the majority of the fungi is
non-viable, since ethidium bromide is a marker of nucleic acids, and the
parasites found do not have nucleic acids in the cell membrane21. The cells are yeast-like, and
spherical, with a diameter ranging from 6 µm to 12 µm; the
cells have birefringent cell membranes and may be isolated or may show
gemmulation, usually presenting with a rosary distribution.
The epidermis can be normal, atrophic, and hyperplasic or ulcerated with
fungi that are located in the hyperplastic bottom25. The evaluation of the dermis infiltrates of
lymphocytes, histiocytes, epithelioid cells, giant cells, plasma cells, and
eosinophils, revealed vasodilation and vascular neoformation. The
histiocytes present sporadically with fungi in their interior, suggesting
that they are phagocytosing the fungi; these cells eventually give rise to
the multinucleated giant Langerhans cells26.
Differential Diagnosis
There are several conditions that may interfere with the diagnosis of
lobomycosis or lacaziosis. These include the more frequently observed keloid
scar27 (Figure 7), other fungal infections, such as
cromomycosis (Figure 8),
sporotrichosis, phaeohyphomycosis, and histoplasmosis, tuberculoid leprosy
(Figure 9), verruciform
elephantiasis resulting from paracoccidioidosis (Figure 10), and diffuse anemia leishmaniasis (Figure 11).
Figure 7 - Keloid scar at 1 year postoperatively after a cesarean
section.
Figure 7 - Keloid scar at 1 year postoperatively after a cesarean
section.
Figure 8 - Chromoblastomycosis: A lesion of chromoblastomycosis that
progressed during a disease course of 25 years. More
characteristic form of the lesion.
Figure 8 - Chromoblastomycosis: A lesion of chromoblastomycosis that
progressed during a disease course of 25 years. More
characteristic form of the lesion.
Figure 9 - Virchow leprosy: keloid nodular lesions observed in the
dorsal region.
Figure 9 - Virchow leprosy: keloid nodular lesions observed in the
dorsal region.
Figure 10 - Elephantiasis nostras verruciformis due to paracoccidioidosi
s: mycosis complicated by repetitive cellulitis in the inguinal
region.
Figure 10 - Elephantiasis nostras verruciformis due to paracoccidioidosi
s: mycosis complicated by repetitive cellulitis in the inguinal
region.
Figure 11 - Anergic diffuse leishmaniasis.
Figure 11 - Anergic diffuse leishmaniasis.
A well-performed clinical history is of paramount importance for the
differential diagnosis, especially in case of diseases associated with
fungal infections, since the clinical evolution of this type of disease is
usually slow, and confusion may arise due to the association with other
events experienced by the patient throughout life.
Treatment
To date, there is no effective treatment for lacaziosis. Several studies have
reported on the surgical treatment and disease relapse, but little is known
regarding the best technique that can be used with respect to the lesion
margins, involvement of other tissues, and the time to disease
recurrence.
Currently the choice of treatment is defined according to the clinical
presentation of the disease. For the unifocal and localized forms, surgical
treatment is performed, followed by treatment with various combinations of
medications, such as clofazimine (50 mg/day), dapsone (100 mg/day), or
itraconazole15, which begins
immediately after surgery and is continued for at least one year, with the
aim to decrease the chances of relapse and eventually achieve a cure.
According to Miranda et al.27,28,
administration of clofazimine in the postoperative period at doses of 300
mg/day in the first month, 200 mg/day in the second month, and 100 mg/day
until completing 24 months of treatment best impedes disease relapse. Some
reports suggested that the disease was cured with the use of
posaconazole29 and of other drug
combinations7.
The best results in the medium term are obtained with surgical treatment,
since it devolves a little of the quality of life of patients who present
with deforming injuries and invoke revulsion30.
Surgical treatment
Several reports describe the surgical treatment of lacaziosis; however, there
are only a few studies on the techniques used during the surgical treatment
of these lesions. Here, we will discuss the surgical aspects of the lesions
of the patients submitted to surgical treatment at the Hospital de Base de
Porto Velho and Hospital Santa Marcelina from June 2006 to July 2014.
Informed Consent
All patients submitted to surgical treatment signed the informed consent form
authorizing the surgery, and anatomopathological assessment and allowed the
dissemination of data regarding the treatment used and the photographs taken
during the course of treatment. This study is registered with the
institutional Ethics Committee under number 48872115.9.0000.0013.
METHODS
From 2006 to 2014, a total of 22 patients, 19 male and 3 female, underwent
surgical treatment. The patients were aged 35–68 years. None of the patients had
relatives with the disease or similar lesions, confirming the findings reported
by Dias et al. in 197022.
A 97-year-old patient diagnosed with the disease 63 years ago was referred to our
clinic for the removal of lesions on the trunk (Figure 12), hands, and penis (Figure 13); he had previously undergone resection of some lesions and was
not aware of the precise number of previous surgeries. He also underwent drug
treatments, without mentioning which.
Figure 12 - Disseminated lobomycosis in a 97-year-old patient.
Figure 12 - Disseminated lobomycosis in a 97-year-old patient.
Figure 13 - Disseminated lobomycosis in a 97-year-old patient.
Figure 13 - Disseminated lobomycosis in a 97-year-old patient.
He did not allow surgeons to remove the lesions that bothered him. This patient
had disseminated lobomycosis, with numerous lesions on the thorax, hands, arms,
legs, and an injury to the body of the penis.
This patient returned 5 years later, with the same complaints and presented with
slight clinical evolution of the nodulations. He did not allow surgical
treatment again; however, the case drew our attention due to the slow evolution
of the pre-existing lesions.
Among the 22 patients who submitted to surgical treatment, the duration of the
disease ranged from 7 years to 45 years.
The clinical presentation in these patients was as follows: the lesion was
located at only 1 site in 9 patients; 10 patients, including 6 male patients,
presented with lesions in only 1 ear and 1 patient presented with a lesion in
the middle third of the right thigh; 3 female patients presented with a lesion
in the right arm, while another presented with a scar on the left lumbar region,
and 1 patient presented with a popliteal cavity lesion; localized form with
local dissemination and/or symmetrical (same injured anatomical structure)
distribution was observed in 11 patients, with lesions being located in both
ears in 3 patients and on the limbs in 7 patients with focal lesions on the
hand, dorsum of the hand, forearm, with multiple nodules of lacaziosis,
suggesting the occurrence of local dissemination, while 1 patient presented with
a lesion in the foot with nodules in the dorsal region of the same foot; and 2
patients presented with the systemic form of lacaziosis, i.e., numerous
disseminated lesions, one of whom refused surgical treatment.
All patients visited our facility with complaints of pruritic nodular lesions,
and 20 of 22 patients had already undergone at least one surgery, with time of
disease recurrence ranging between 5 months and 6 years. Two patients has not
undergone any surgical and clinical treatment previously and presented with slow
growing pruritic nodular lesions; they had developed the lesions following
insect stings approximately 1.5 years ago.
Twenty-one patients were rural workers, and only 1 lived in the countryside, but
it was of the home.
Surgery
All patients underwent clinical and laboratory assessment, prior to the
surgery; the following tests were performed: blood workup, estimation of
urea, creatinine, and blood glucose levels, coagulation tests, and
electrocardiography. Patients who were administered local or regional
anesthesia were evaluated by the anesthesia team.
Lesions in the ears
In patients with ear lesions, we were able to confirm that injuries do not
invade the cartilage, affecting only the skin and subcutaneous tissue during
the surgical treatment (Figures 14 and
15); this has already been
reported in the available literature.
Figure 14 - Lesion of the right ear (preoperative).
Figure 14 - Lesion of the right ear (preoperative).
Figure 15 - Dissection of the lesion showing intact auricular
cartilage.
Figure 15 - Dissection of the lesion showing intact auricular
cartilage.
The cartilage in all cases had a normal macroscopic aspect. Among patients
who had undergone surgical treatment of lesion in this regions, many
presented with partial resection of the ear lesions, including the
cartilage, being the withdrawal of existing lesions and the reconstruction
of the pinna performed at the same surgical time, when possible.
In patients with lesions in the forearm, the nodular lesions on the arm and
hand were resected; these lesions were circumscribed lesions and did not
invade the adjacent tissues, blood vessels, muscles, and tendons (Figure 16 and 17).
Figure 16 - A lesion in the dorsal region of the right hand.
Figure 16 - A lesion in the dorsal region of the right hand.
Figure 17 - Dissection of a nodular lesion of lobomycosis circumscribed
to the dorsal region of the hand with no invasion of the tendons
and /or other tissues.
Figure 17 - Dissection of a nodular lesion of lobomycosis circumscribed
to the dorsal region of the hand with no invasion of the tendons
and /or other tissues.
DISCUSSION
The patients who submitted to surgical treatment received no adjuvant treatment.
Twenty of the 22 patients were already administered medication for lobomycosis,
without any significant improvement. They refused medication due to the
difficulty presented in receiving the medication, which is a prolonged
treatment. In our 8-year experience of operating on and monitoring these
patients, we noticed that disease relapse will occur, but there is no specific
time for disease relapse. Among the 11 patients who returned to our facility for
follow-up, 9 presented with disease relapse; the time of relapse ranged from 5
months to 6 years. The remaining patients, or are recent cases, or did not
return for follow-up.
In many case, disease recurrence, such as small nodules and/or nodules along the
affected limb, was noted on the grafted areas. Surgical margins were 0.5 cm of
the lesion edge and the deep margin; the deeper tissues were not affected.
Lobomycosis is a deforming disease that deprives patients of social conviviality,
and surgery is the only effective treatment for the removal of the lesions,
although it is a temporary option. Patients are informed about relapses, and
surgery is always the chosen option to relieve them of the discomfort caused by
the presence of the lesions.
CONCLUSION
We confirm that surgery is one of the effective treatments for lacaziosis. All
the characteristics described in the literature were confirmed, namely, the
lesions did not affect the other tissues, such as blood vessels, tendons, and
cartilage.
We could not confirm whether the dissemination route of the disease was
lymphatic, hematogenic, or contiguity. We suggest that the disease recurrence
occurred in the grafted areas because greater deep margin resection could not be
performed without damaging the adjacent tissues.
Little is known about lacaziosis and its pathogenesis; it is a rare disease
without an effective clinical treatment. Plastic surgery units should be
responsible for the surgical treatment of this disease, which, when indicated,
preserves noble structures, such as auricular cartilage, and restores the
patients’ self-esteem and dignity, albeit temporarily.
COLLABORATIONS
RLK
|
Analysis and/or data interpretation, conception and design study,
final manuscript approval, investigation, methodology, realization
of operations and/ or trials, supervision, visualization, writing -
original draft preparation, writing - review & editing.
|
CFJ
|
Analysis and/or data interpretation, conception and design study,
data curation, investigation, methodology, visualization, writing -
review & editing.
|
AEKC
|
Data curation, investigation, realization of operations and/or
trials, writing - review & editing.
|
LFF
|
Analysis and/or data interpretation, data curation, realization of
operations and/or trials, writing - review & editing.
|
ASP
|
Analysis and/or data interpretation, data curation, investigation,
validation.
|
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1. Universidade Federal de Rondônia, Porto Velho,
RO, Brazil
2. Hospital de Base Ari Pinheiro, Porto Velho, RO,
Brazil
3. Centro De Medicina Tropical, Porto Velho, RO,
Brazil.
Corresponding author: Rodolfo Luis
Korte Rua Anizio Gorayeb, nº 1331 - Porto Velho, RO, Brazil Zip Code
76803-680 E-mail: rlkorte@uol.com.br
Article received: May 5, 2018.
Article accepted: November 11, 2018.
Conflicts of interest: none.