Tropical pathology of the oral mucosa

TROPICAL PATHOLOGY OF THE ORAL MUCOSA - Capítulo do livro: Oral Diseases. Textbook and Atlas. Lotti, TM, Parish LC & Rogers III RS (eds.) Berlin: Springer-Verlag;1999:129-147

Clarisse Zaitz, MD1
Marcia Ramos-e-Silva, MD2

1 Associate Professor of Dermatology - Santa Casa de Misericórdia de São Paulo, School of Medicine, São Paulo, Brazil
2 Associate Professor of Dermatology - Universidade Federal do Rio de Janeiro, School of Medicine, Rio de Janeiro, Brazil

PARACOCCIDIOIDOMYCOSIS
SOUTH AMERICAN BLASTOMYCOSIS
BRAZILIAN BLASTOMYCOSIS
LUTZ'S MYCOSIS

DEFINITION: Paracoccidioidomycosis is a rural endemy, that mainly affects male workers (15:1) between the ages of 29 and 40 years, being rare in children. The sites involved are the lungs, oral, nasal, and gastrointestinal mucous membranes and the lymphatic system.

ETIOLOGY: Paracoccidioides brasiliensis is a saprophytic dimorphic fungus. It is an eucariotic cell with a chitin wall, that likes humid places, with land rich in proteic material and minimal temperature variation. It has been isolated from sand in endemic areas. Man is its only natural host, in Central America and South America with the exception of Chile.

PATHOGENESIS: Invasion is mainly pulmonary by spore inhalation, but there are reports of cutaneous, oral or ano-genital mucosal inoculation. Transmission man to man is unknown, and familial cases are rare. Dissemination occurs either by lymphatic and hematogenic path or by contiguity.

The immunological state of the patient will determine the degree of severity of the disease. Depending on this immunological response, the patient will have the infection without disease; a benign, localized disease, that can be cured spontaneously; or a severe, chronic, generalized disease, which is the more common form.

ORAL MANIFESTATIONS: In the mucous membranes, especially the mouth, the characteristic lesion is an erythematous ulcer with hemorrhagic and granular dots. Macrocheilitis, infiltrations, and vegetations can also be present. Sialorrhea is frequent.

ASSOCIATED FINDINGS: Cutaneous inoculation is very rare. Most skin lesions occur either by hematogenic or lymphatic dissemination and are papules, tubercles, vegetations, or ulcers. At the base of the ulcer, hemorrhagic dots as the ones on oral ulcers can be seen. Regional or generalized adenopathy is usually present, and the lymph nodes develop fistules. Pulmonary paracoccidioidomycosis occurs in ninety percent of the cases, affecting both lower half of the lungs and, in twelve percent of the cases, there is association with tuberculosis. Besides skin, other organs commonly involved are: gastrointestinal system, liver, spleen, central nervous system and adrenals.

MICROSCOPIC FINDINGS: The parasite when inside the lymph node appears as a round cell, has a double refringent wall, appears with or without single or multiple budding, and is 5 to 25 micra in diameter. With some stains other than hematoxylin-eosin, the so-called "pilot wheel" aspect can be seen because of the cryptosporulation or multiple exosporulation reproduction of the fungus.

Histopathological structure, a uniform pattern in all affected organs, is similar to other inflammatory chronic diseases. The difference is the finding of the fungus better seen with silver methenamine or PAS stains. This paracoccidioidic granuloma is an immunospecific tissue response type IV or cellular hypersensitivity reaction against the fungal antigens, which destroy or block it, that has a tuberculoid pattern, showing foreign body and Langhans type giant multinucleated cells, sometimes very numerous, of variable sizes. The fungus inside giant cells can be degenerated, latent, or in active reproduction by simple or multiple budding.

DIAGNOSIS: Clinical diagnosis can be confirmed by mycological exam, both direct and culture, and histopathology. The paracoccidioidin test can be some of aid.

The direct exam of materials from the lesions reveals round forms, with a double contour membrane, single or multiple budding and sometimes a 'pilot wheel' appearance. In agar-Sabouraud and agar-blood, at room temperature, growth of a white colony, adherent to the medium is slow (20 to 30 days). The microscopy of these colonies shows thin septated micelial filaments with terminal or intercalated spores. At 37o C, mainly in enriched media, the colony acquires a cerebriform or leveduriform surface and its microscopy reveals round cells, similar to the ones found in tissues.

Histopathology shows the granuloma and, with Grocott and PAS stains, the fungi can be easily visualized. Paracoccidioidin test can be useful, but it is also positive in inapparent infection.

DIFFERENTIAL DIAGNOSIS: Sometimes, it is difficult to clinically differentiate paracoccidioidomycosis from leishmaniasis, cutaneous tuberculosis, and lethal midline granuloma but usually laboratory studies confirm the diagnosis.

TREATMENT: Among sulfonamides, sulfamethoxipyridazine, 500-1000mg per day, can be used for two years. Intravenous amphotericin B, reserved for severe cases, is given daily or on alternate days, in glucose as a slow infusion over several hours. The total dosage is 2-4g.

Oral and daily administration of ketoconazole, 200-400mg, fluconazole, 150-300mg, or itraconazole 200-400mg is also effective.

Fig1. Paracoccidioidomycosis. Erythematous ulcer with hemorrhagic dots on the palate.
Fig2. Paracoccidioidomycosis. Erythematous ulcer with hemorrhagic dots on the tongue.
Fig3. Paracoccidioidomycosis. Macrocheilitis, infiltration and vegetation on the lip.
Fig4. Paracoccidioidomycosis. Gengivitis and erythema of the oral mucous membrane.
Fig5. Paracoccidioidomycosis. Round forms with a double contour membrane. "Pilot wheel" appearance. Direct exam.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:153-5.
2. Franco M, Lacaz CS, Restrepo-Moreno A, Del Negro G. eds. Paracoccidioidomycosis. Boca Raton:CRC Press, 1994.
3. Hay RJ, Roberts SOB, MacKenzie DWR. Mycology. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1127-216.
4. Kwon-Chung KJ, Bennett JE. Medical Mycology. Malvern:Lea & Febiger, 1992:594-619.
5. Lacaz CS, Porto C, Martins JEC. Micologia médica. 8ed. São Paulo:Sarvier, 1991:248-92.
6. Negroni R. Paracoccidioidomycosis (South American Blastomycosis, Lutz's Mycosis). Int J Dermatol 1993;32(12):847-59.
7. Padilha-Gonçalves A. Paracoccidioidomycosis. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:61-9.
8. Parish LC, Witkowski JA, Vassileva S. Color Atlas of Cutaneous Infections. Turin:Blackwell Science, 1995:139-40.
9. Restrepo A. Treatment of tropical mycoses. J Am Acad Dermatol 1994;31(3 Pt 2):Suppl.91-102.
10. Rippon JW. Medical Mycology. 3ed. Philadelphia:W.B. Saunders, 1988:506-31.
11. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:343-58.
12. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:97-8.
13. Shadomy HJ, Utz JP. Deep fungal infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2468-97.

MYIASIS

DEFINITION: Myiasis is an infestation of any part of the skin and mucous membrane by the larvae of Diptera, especially flies. It is mainly a domestic animal disease, but it can accidentally infest man.

ETIOLOGY: There are two types of cutaneous myiasis: the cavitary form, caused mostly by the genera Chrysomyia, Calliphora, Lucilia, Musca, Phormia, Sarcophaga and Wohlfarhrtia, and the furunculoid form, produced by the genera Hypoderma, Gasterophilus, Dermatobia, Callitroga, Chrysomyia, and Cordylobia.

PATHOGENESIS: In cavitary myiasis, the larvae infest decaying flesh. Furunculoid myiasis affects living flesh. The parasite is an obligatory myiasis producer, because its larvae need to parasite skin in order to complete its biological cycle. In Central and South America, the species most frequently responsible for furunculoid myiasis is Dermatobia hominis.

ORAL MANIFESTATIONS: Cavitary myiasis shows many larva in suppurating tissues that show marked marked destruction. Sometimes, it also affects the upper respiratory tract. There are mild to severe constitutional symptoms and eosinophilia.
In furunculoid myiasis, there is one or more papules or nodules. Each one of them has a larva inside. There is discrete discomfort, pruritus, and a slight movement of the larva at the opening of the lesion can be observed.

ASSOCIATED FINDINGS: They are the same as in the oral infestation.

DIAGNOSIS: Cavitary myiasis is diagnosed by the finding of multiple larva in ulcers. Furunculoid myiasis is diagnosed by the observation of the movement of the only larvae at the opening of the lesion.

DIFFERENTIAL DIAGNOSIS: Both cavitary and furunculoid myiasis are easily diagnosed by the finding of the larva or observation of movement. When there are few larva in cavitary myiasis that are not promptly found, the lesion looks like an ulcer sometimes very extensive.

TREATMENT: Removal of all larva is the most important objective of treatment. From cavitary myiasis, they can be removed by the application of ether, that makes the larva come out, and extraction with a fine forceps. Furunculoid myiasis can be extracted either by pressure with fingers or by application of a thick layer of solid vaseline. The larvae comes out, penetrates into the vaseline, leaving the skin. In rural areas, people apply a piece of pork fat on top of the lesion, for the same effect. In more difficult cases, it can be removed by surgery.

Fig1. Furunculoid myiasis. Nodule with larva inside on the tongue.
Courtesy of Alberto Eduardo Cox Cardoso, MD, Maceió, Brazil
Fig2. Furunculoid myiasis - Two larvae.
Fig3. Furunculoid myiasis - Nodule with larvae on the cheek.
Courtesy of Ivo Bussoloti Filho, MD, São Paulo, Brazil.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:168-9.
2. Burns DA. Diseases caused by arthropods and other noxious animals. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1265-324.
3. Canizares O. Myiasis. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:404-11.
4. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:373-88.
5. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:140-1.
6. Wilson DC, Leyva WH, King Jr LE. Arthropods bites and stings. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993: 2810-26.

LEPROSY (HANSEN'S DISEASE)

DEFINITION: Leprosy is a chronic curable disease with good prognosis related to life, but incapacitating. Of 20 million cases in the world, it is estimated that only 2 million are under treatment. Over the centuries, there was a wide geographical variation, but today it is considered endemic in tropical and subtropical areas.

ETIOLOGY: Mycobacterium leprae is a small slightly curved rod that turns red by Gram and acid-fast Ziehl-Neelsen stain. It is an intracytoplasmic parasite of macrophages where it can be isolated or forming globoid masses, called globia, in skin and peripheral nerves, sparing central nervous system. It only affects man, although it has been found and reproduced in the armadillo, monkey, and mouse.

PATHOGENESIS: Incubation period is long, lasting from 2 to 7 years. Spread of bacilli occurs through nasal drops or open lesions of bacilliferous patient into nasal mucosa or open lesions on the skin of healthy individuals. In 1966, Ridley and Jopling classified leprosy, based on the notion of polar forms, first described by Rabello (1953), into lepromatous leprosy, at one end, and tuberculoid leprosy, at the other, with the three types of borderline leprosy in between: one tending to the immune-depressed end, BL group, one in the middle, BB group, and one tending to the immunocompetent side, BT group.

Specific cell-mediated immunity eliminates the bacilli in most people and this response can be detected by the lepromine test. Because clinical form depends on late immunity reaction, it can make the disease progress without restraint, limit itself or cure spontaneously. Humoral immunity is difficult to evaluate but it is increased in forms that have low cell mediated response.

ORAL MANIFESTATIONS: Oral manifestations may occur in the lepromatous and borderline form. Nodules (lepromas), plaques, papules, and ulcers can be present. Main sites are the hard and soft palate, dorsal aspect of the tongue, lips, and gingiva.

ASSOCIATED FINDINGS: All forms affect skin and present thickened nerves, alterations in sensibility to pain, temperature and touch, motor, trophic, vasomotor and secretory disturbances.

Lepromatous leprosy, which is the most contagious form, shows multiple, erythematous macules, papules, nodules, and plaques. There are ill-defined borders usually bilateral with a tendency to symmetry. Patients sometimes have bilateral infiltration of the earlobes, madarosis and desquamation of the legs.

The tuberculoid form shows few lesions and can be only neural. Lesions are papular or plaque-like with well-defined borders and depressed centers. They are usually hypopigmented in black skin, and erythematous in white skin. Lesions are usually hairless and unilateral bone reabsorption may be present.

The borderline form has features inbetween the lepromatous and tuberculoid forms. It is asymmetrical. A unilateral earlobe infiltration may occur. The severity of skin and nerve alteration depends on the side of the spectrum the patient is (BL, BB or BT). Hair also does not grow on the lesion.

MICROSCOPIC FINDINGS: There are three basic histopathological structures: the lepromatous, the tuberculoid, and borderline structure. Lepromatous structure shows an infiltrate in the dermis, hypodermis and internal organs with Virchow cells, that are macrophages with many bacilli and lipid drops in their cytoplasm. In hematoxylin-eosin stain, these cells have a foamy appearance. Bacilli, isolated or in globi, can be detected by the Ziehl-Neelsen or Wade stain. Sudan III and Scarlet R can show the fat inside the Virchow cells. A normal aspect band, called Unna band, separates the epidermis from the infiltrate composed of lymphocytes and plasmocytes.

Tuberculoid structure has a dermal infiltrate that can touch epidermis, showing an aspect of nodules of epithelioid cells. There are lymphocytes at the edges and Langhans giant cells at the center of the granuloma.

Borderline structure shows features of Virchow cell infiltrate (LL) and of tuberculoid granuloma (TT). The predominance of one or other depends if it is the BL, BB, or BT. There can be three histopathological situations in this form: first, the patient has some lesions with lepromatous structure and others with tuberculoid structure; the second, shows, in the same biopsy, Virchow and tuberculoid areas, and the third has a mixed structure of foamy and epithelioid cells.

All three forms of leprosy show alteration in skin nervous structures.

DIAGNOSIS: The diagnosis of the disease and its forms is made by the finding of the bacilli in cutaneous lymph and nasal secretion. Ziehl-Neelsen stain is used and only the presence of globia is diagnostic. They are found in 100% of lepromatous leprosy, in 75% of borderline and only in 5% of tuberculoid.

Other tests used are evaluation of thermic, pain and tactile sensitivity, histamine, pilocarpine and Mitsuda test, which is an intradermal reaction that is read 21 to 28 days after the injection and can also be positive in 80% of the general population older than 19 years in endemic areas.

Also for diagnosis, a skin and sometimes a nerve biopsy is performed and there are some other test that can be used.

DIFFERENTIAL DIAGNOSIS: Oral manifestations of leprosy can be diagnosed as lymphoma, tertiary syphilis, lethal midline granuloma. Features on other sites and the biopsy are usually diagnostic.

TREATMENT: Multidrugtherapy is used, with the recommendations of the World Health Organization. Bacilloscopy is perform in three to five different sites on the skin. The patient is considered paucibacillary if no bacillus is found and is then treated with rifampicin (600mg/month) and dapsone (100mg/day) for 6 months. If there is one or more bacilli, the patient takes rifampicin (600mg/month), dapsone (100mg/day) and clofazimine (300mg/month plus 50mg/day) for 2 years. Some new drugs in different associations, as pefloxacin (800mg/day), ofloxacin (400mg/day), claritromycine (500mg/day), and minocycline (100mg/day), are in research.

Fig1. Lepromatous Leprosy. Plaque of leproma on the palate. Courtesy of Sinésio Talhari, MD, Manaus, Brazil.
Fig2. Lepromatous Leprosy. Plaque covered by pseudomembranous material on the palate. Courtesy of Ivo Bussoloti Filho, MD, São Paulo, Brazil.
Fig3. Borderline Leprosy - Erythema and infiltration of the lip.
Fig4. Leprosy. Bacilli in cutaneous lymph. Presence of globia. Ziehl-Neelsen stain.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:124-32.
2. Bryceson ADM. Leprosy. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1065-83.
3. Canizares O, Harman R, Adriaans B. Leprosy. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:165-200.
4. Grosset JH. Progress in the chemotherapy of leprosy. Int J Lepr 62(2):268-76.
5. Laskaris G. Color Atlas of Oral Diseases. Stuttgart:Georg Thieme Verlag, 1988:134-5.
6. McDougall AC, Ulrick MI. Mycobacterial disease: Leprosy. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2365-410.
7. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:287-310.
8. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:22-36.

MUCO-CUTANEOUS LEISHMANIASIS

DEFINITION: Leishmaniasis is an infectious disease that affects mainly skin, mucous membranes, and lymph node. Usually, it does not affect the internal organs or the central nervous system.

ETIOLOGY: It is caused by a protozoa of the genus Leishmania. Transmission occurs through the bite of an infected female mosquito, mainly of the genera Phlebotomus and Lutzomya. The classification of the species of the genus Leishmania is still controversial. Some suggested only one species causes different clinical forms and others classify this genus into various species each one causing one form of the disease, cutaneous, muco-cutaneous, visceral or kalazar, and anergic forms.

PATHOGENESIS: The clinical classification is made by the type of lesion, species of Leishmania, and mosquito involved. Also the immunological state of the patient and the evolution and the prognosis of leishmaniasis depend basically on the cell mediated response. Depending on the state of this response, it may lead to clinical and even biological cure or to more severe forms.

There are two types of transmission: the sylvestral, in which the reservoirs are wild animals, and man becomes infected when he invades the forests and is bitten by the mosquito, and the urban type, where the biological cycle occurs in domicile or peri-domicile area and the reservoir is the sick man or domestic animals.

Promastigota, flagellated form or leptomonas, is transmitted to animals or healthy man by the female mosquito, that needs warm blood to mature its ovarian follicles. In the affected man or animal, it changes into amastigota or ovoid aflagellated form, called leishmania, which can again be transmitted to a female mosquito. This is the form found in tissues.

ORAL MANIFESTATIONS: Mucous membranes may also be affected after the hematogenic dissemination. The mouth, nose, larynx, and pharynx are mostly involved. There are infiltrative, ulcerous, vegetating, and atrophic-crusted lesions. Infiltration of the upper lip and nasal region give a tapiroid appearance. Parrot beak-like nose is caused by partial destruction of the sub-septum. Gangosiform aspect is present when oral and nasal cavities form a unique cavity. Deforming osteoarthritis occurs with severe ulcero-cicatricial involvement.

ASSOCIATED FINDINGS: There is an incubation period ranging from 3 weeks to many months, before a lesion appears at the site of inoculation. The predilection site is the leg. There can be a erythematous area, edema, papule, tubercle, or ulcer, from millimetres to centimeters and there may be a discrete lymphangitis and adenopathy. Hematogenic dissemination is responsible for other skin lesions called leishmanids, of variable number and sizes that are papulo-crusted, ulcero-crusted, papulo-follicular, tuberous or vegetating.

MICROSCOPIC FINDINGS: The characteristic finding is a granuloma structure with leishmania in macrophages.

DIAGNOSIS: Laboratory examinations should be performed when clinical aspect of the lesion and patient's origin suggests this diagnosis. Direct examination using Giemsa stain will show amastigota form inside macrophages in 100% of smears taken from recent lesions. Culture is performed in NNN medium where promastigota or leptomonas, the flagellated form grows.

Histopathology can be diagnostic by the observation of very small oval structures inside the macrophages: amastigota or ovoid form of the parasite.

Montenegro test, an intradermal reaction of a suspension of leptomonas or antigenic fractions of leishmania and read after 48 to 72 hours, will be positive forever after inoculation. Indirect immunofluorescence reveals antibodies anti-Leishmania, and anti-Trypanosoma cruzi as a cross reaction

DIFFERENTIAL DIAGNOSIS: Paracoccidioidomycosis, squamous cell carcinoma, lethal midline granuloma and Wegener's granuloma can differentiated by biopsy and the finding of leishmania.

TREATMENT: Glucantime, an antimonial, in a dosage of 0,1g/kg/day in two series of 30 days, either intramuscular or intravenous, with a two weeks interval, is still the medication used for leishmaniasis. For more severe cases, amphotericin B, 1mg/kg/day in dextrose, in a very slow intravenous application with maximum total dose of 2g, is used. More recently two drugs: intramuscular pentamidine, an aromatic diamine, 2,5mg/kg used in ten daily or alternates days applications; and oral itraconazole, in a dosage of 400mg/day, have been used with very good results. Another one, paromycin, is still in trial for topical and systemic use.

Fig1. Muco-cutaneous Leishmaniasis - Infiltration of the palate.
Fig2. Muco-cutaneous Leishmaniasis - Destruction of the palate. Oral and nasal cavities form an unique cavity.
Fig3.Muco-cutaneous Leishmaniasis - Tongue with infiltrative and vegetating aspect.
Fig4. Muco-cutaneous Leishmaniasis - Vegetating and infiltrative lesion on the lip.
Fig5. Muco-cutaneous Leishmaniasis - Amastigota or ovoid forms of the parasite inside the macrophages.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:159-65.
2. Bryceson ADM & Hay RJ. Parasitic worms and protozoa. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1217-64.
3. Farad SF, Klaus SN, Frankenburg S, Klion AD, Nutman TB. Protozoan and helminth infection. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2769-87.
4. Kerdel-Vegas F, Kerdel F. American leishmaniasis. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:301-12.
5. Laskaris G. Color Atlas of Oral Diseases. Stuttgart:Georg Thieme Verlag, 1988:146-7.
6. Parish LC, Witkowski JA, Vassileva S. Color Atlas of Cutaneous Infections. Turin:Blackwell Science, 1995:163-6.
7. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:373-88.
8. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:110-3.

DONOVANOSIS
GRANULOMA VENEREUM
GRANULOMA INGUINALE

DEFINITION: Donovanosis is a sexually transmitted disease of the tropical and subtropical disease, that affects mostly the anal and genital areas.

ETIOLOGY: It is caused by an Gram negative intestinal saprophyte, Calymmatobacterium (Donovania) granulomatis.

PATHOGENESIS: In general but not exclusively, it is considered a sexually transmitted disease, mainly of homosexual males, with low social economical level, and in theirs 20 to 45 years of age. Hematogenous dissemination is rare.

ORAL MANIFESTATIONS: Oral manifestations are very rare. Unilateral, chronic, progressive and indolent ulcers with satellite lesions caused by autoinoculation are the characteristic findings. The initial lesion is a small indurated nodule that soon ulcerates and becomes a painless shallow ulcer with some vegetation, that easily bleeds. There is a serous exudate and destructive lesions can extend to many centimeters.

ASSOCIATED FINDINGS: In men, it generally affects the prepuce, glans or anal area and, in women, the labium minora or majora and less frequently the inguinal and anal regions. There is no adenopathy and sometimes elephantiasis of the scrotum or esthiomene occurs resulting from the cicatricial process.

MICROSCOPIC FINDINGS: In histopathology, small rods can be found inside the macrophages.

DIAGNOSIS: The diagnosis is confirmed by the finding of the agent in direct exam with either Giemsa or Wright stains. Inoculation of the material in the vitelin sac of chicken embryo can be performed.

DIFFERENTIAL DIAGNOSIS: Oral syphilitic chancre, ulcerous tuberculosis, and squamous cell carcinoma are easily differentiated when the agent is found.

TREATMENT: Streptomycin, 1-2g/day for 10-20 days, tetracycline, 2g/ day for 15-20 days or sulfamethoxazol, 800mg, and trimethoprim, 160mg, twice a day for 15-30 days are used. Erythromycin, gentamicin, minocycline, ampicillin and others can also be employed in case of allergy.

Fig1. Donovanosis - Ulcerated an vegetating lesion on anal region. Courtesy of Cleide Ishida, MD, Rio de Janeiro, Brazil
Fig2. Donovanosis - Infiltration of the lip. Courtesy of Cleide Ishida, MD, Rio de Janeiro, Brazil.
Fig3. Donovanosis - Irregular ulcer on the oral mucous membrane of the lip. Courtesy of Cleide Ishida, MD, Rio de Janeiro, Brazil.
Fig4. Donovanosis - Irregular ulcers on the palate. Courtesy of Cleide Ishida, MD, Rio de Janeiro, Brazil.
Fig5. Donovanosis - Small rods inside the macrophages. Giemsa stain. Courtesy of Cleide Ishida, MD, Rio de Janeiro, Brazil.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:196-7.
2. Canizares O, Olansky S, Olansky A, Olansky D. Donovanosis. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:504-9.
3. Highet AS, Hay RJ, Roberts SOB. Bacterial infections. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:953-1031.
4. Rothenberg RB. Granuloma inguinale. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2757-9.
5. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:279-86.
6. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:77-8.

SYPHILIS

DEFINITION: Syphilis is an exclusive human treponemal venereal disease that leads to cutaneous and internal lesions.

ETIOLOGY: The agent is a flagellated and very mobile spirochete, Treponema pallidum, morphologically and serologically identical to others treponemas.

PATHOGENESIS: Transmission can be sexual, congenital, or by other contacts. There is no predilection for either sex and it is universal with a higher incidence in the tropical areas because of the low social-economical level. Its incidence increases depending upon the human sexual behavior. Penetration occurs through mucous and semimucous membranes. There are two forms, each one with various phases: sexually transmitted, with recent (primary and secondary), latent and late (tertiary) phases, and congenital, with recent and late phases.

Initial lesions are caused by cellular and vascular responses to the agent. These lesions disappear and usually 2 to 3 months and later there is a immunocomplex deposition, that causes a generalized eruption. The late phase is characterized by an intense hypersensitivity reaction.

ORAL MANIFESTATIONS: Oral lesions may appear in all phases. In recent, primary phase, if the inoculation site was the oral mucosa, a typical chancre appears 3 to 4 weeks after penetration, as a round, painless superficial ulcer with a raised and endured border. During the secondary period of recent phase, mucous patches may be present. Gummatous ulcer, characteristic lesion of late syphilis, may occur in the mouth during this phase, as well as leukoplasia, hard palate perforation, superficial and interstitial glossitis.

In recent congenital syphilis, mucous patches and oral radiated fissures be present.

ASSOCIATED FINDINGS: The initial chancre has the same characteristic as in the mouth and is more frequent in genital areas. Usually there is bilateral, painless, regional poliadenopathy. Spontaneous involution occurs in 1 to 4 months. Secondary syphilis arises as a generalized monomorphous asymptomatic eruption. The patient may have poliadenopathy, muscular pain, discrete fever, headache, pharyngitis, and palmo-plantar involvement. This generalized eruption, called syphilides, can be erythematous (roseola), papular, papulodesquamative (psoriasiform) or follicular (lichenoid). In this phase, patchy alopecia, anal and genital lesions (condylomata lata), madarosis and paronychia may occur. The late phase is characterized by nodular an/or gummatous lesions on the skin, skeletal, eye, cardiovascular, and nervous system involvement.

Congenital syphilis, when transmitted early in pregnancy, aborts the fetus or death at birth occurs. If transmission occurs later during pregnancy, the affected children are underweight and pale. A bullous eruption, particularly of palmo-plantar region, may be followed by a maculopapular or papulopustular generalized eruption. In its late phase there are gummatous and nodular lesions, painful bone involvement, keratitis, deafness and articular alterations. Severe active congenital syphilis may lead to characteristic signs that are saddle nose, Hutchinson teeth, high arched palate, atrophy of upper maxilla, mulberry molar, and others.

MICROSCOPIC FINDINGS: Histopathology of early syphilis may reveal some treponema around vascular walls and an intense vasculitis with a dense infiltrate of lymphocytes and plasmocytes. Usually during secondary period treponema are present as well as an infiltrate of hystiocytes, lymphocytes and numerous plasmocytes. In late syphilis a granuloma with no treponema and sometimes caseous necrosis is found.

DIAGNOSIS: Finding of treponema in early phase confirms diagnosis. Dark field observation, silver impregnation (Levaditi and Warthin-Starry stains) and direct immunofluorescence may help this search. VDRL (venereal disease research laboratory) and FTA-abs (fluorescent treponema antibody absorption) are the serological tests most widely used. When nervous system involvement is suspected liquor exam must be performed.

DIFFERENTIAL DIAGNOSIS: Depending on the phase, oral lesions may be confused with a variety of disease. Syphilitic chancre may resemble aphtha, leishmaniasis and ulcerous tuberculosis; mucous patches may mimic candidosis, lichen planus, lupus erythematosus; gummatous lesions can be confused with squamous cell carcinoma, paracoccidioidomycosis, and other types of ulcers. Serological tests confirms the diagnosis. Late syphilis is the phase most difficult to diagnose.

TREATMENT: Treatment of choice is benzathin penicillin in an intramuscular single dosage of 2.4 million units for primary syphilis, 4.8 million units for secondary syphilis and 12 million units for tertiary syphilis divided in ten days. For neurosyphilis procaine or aqueous penicillin must be used because benzathine does penetrate hemato-encephalic barrier. Congenital syphilis is treated intramuscular or intravenously with 50 thousands units/kg/day for 10 days of aqueous or procaine penicillin. For patients with allergy to penicillin, erythromycin or tetracycline, in a dosage of 2g/day for 30 days can be administered.

Fig1. Recent Syphilis - Primary period - Chancre - Round ulcer with an endured border on the oral mucosa.
Fig2. Recent Syphilis - Primary period - Chancre - Round ulcer with an endured border on the tongue. Courtesy of Ivo Bussoloti Filho, MD, São Paulo, Brazil.
Fig3. Recent Syphilis - Secondary period - Mucous patches on the tongue. Courtesy of Iphis Campbell, MD, Brasília, Brazil.
Fig4. Recent congenital Syphilis - Mucous patches and oral radiated fissures.
Fig5. Recent Syphilis - Treponema in dark field observation.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:137-43.
2. Laskaris G. Color Atlas of Oral Diseases. Stuttgart:Georg Thieme Verlag, 1988:124-30.
3. Morton RS. The treponematoses. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1085-126.
4. Olansky S, Olansky A, Olansky D. Venereal Syphilis. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:509-24.
5. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:311-26.
6. Sanchez M, Luger AFH. In: Syphilis. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2703-43.
7. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:70-3.

ORAL CANDIDOSIS
MONILIASIS

DEFINITION: Candidosis is a primary or secondary infection involving yeasts of the genus Candida, which are normal inhabitants of the alimentary tract and the mucocutaneous regions.

ETIOLOGY: Candida albicans is the predominant yeast of genus Candida found in most oral candidiasis. Other species, also representing normal flora of mucocutaneous areas, can be pathogenic (C. tropicalis, C. krusei, and others).

PATHOGENESIS: Varying predisposing factors and general conditions in which normal equilibrium between Candida and host may be sufficiently disturbed to lead to a pathologic state: a) extreme youth; b) pregnancy; c) administration of steroids; d) endocrine dysfunctions; c) diabetes; f) prolonged administration of antibiotics; g) immunosuppressive agents; h) drug abusers; i) accidental barriers breaks such trauma, burns and others; and j) general debility (genetic, iatrogenic and acquired).

ORAL MANIFESTATIONS: A cream-white to grey pseudomembrane covers the tongue, soft palate, buccal mucosa and the oral surfaces. Erythematous candidiasis is usual in AIDS patients as well as in old people who may also present chronic cheilitis.

ASSOCIATE FINDINGS: Patients with general debility could develop systemic disease.

MICROSCOPIC FINDINGS: Direct examination is composed of necrotic material, leukocytes, loose epithelial cells, bacteria, and food material along with intertwined pseudohyphae and hyphae yeast cells.

DIAGNOSIS: Diagnosis is made through clinical signs and symptoms, mycological examination and histopathologic appearance and depends on demonstration of the organism.

DIFFERENTIAL DIAGNOSIS: In some patients, leukoplakia, lichen planus, tertiary syphilis, and other lesions resemble cutaneous candidiasis.

TREATMENT: As candidosis is primarily an opportunistic infection, prognosis depends almost entirely on the type and severity of the predisposing conditions or diseases.

Topical treatment has been considered of choice with the use of one per cent crystal violet, one per cent nystatin, amphotericin B suspensions, clotrimazole, ketoconazole or econazole cream.

New oral agents in a single dosage, such as ketoconazole (200-400mg), itraconazole (200-400mg) and fluconazole (150-300mg) can be prescribed. For more severe and extensive infections, intravenous amphotericin B (1mg/kg/day in dextrose with maximum total dose of 2g), can be administered very slowly.

Fig1. Oral Candidosis - Cream-white pseudomembrane plaques on the tongue.
Fig2. Oral Candidosis - Cream-white pseudomembrane plaques cover the tongue.
Fig3. Oral Candidosis - Erythematous candidiasis on the palate and chronic cheilitis.
Fig4. Oral Candidosis - Chronic cheilitis.
Fig5. Oral Candidosis - Pseudohyphae and hyphae yeast cells. Direct examination. Gram stain.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:150-2.
2. Canizares O. Candidiasis. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:34-7.
3. Hay RJ, Roberts SOB, MacKenzie DWR. Mycology. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1127-216.
4. Kwon-Chung, KJ, Bennett JE. Medical Mycology. Malvern:Lea & Febiger, 1992:280-336.
5. Lacaz CS, Porto C, Martins JEC. Micologia médica. 8ed. São Paulo:Sarvier, 1991:216-24.
6. Laskaris G. Color Atlas of Oral Diseases. Stuttgart:Georg Thieme Verlag, 1988:138-43.
7. Martin AG, Kobayashi GS. Yeast infections: candidiasis, pytiriasis (tinea) versicolor. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2452-67.
8. Parish LC, Witkowski JA, Vassileva S. Color Atlas of Cutaneous Infections. Turin:Blackwell Science, 1995:121-25.
9. Rippon JW, Medical Mycology. 3ed. Philadelphia:W.B. Saunders, 1988:532-81.
10. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:327-42.
11. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:90-1.

ENTOMOPHTHOROMYCOSIS CONIDIOBOLAE
CHRONIC RHINOFACIAL ZYGOMYCOSIS RHINOENTOMOPHTHOROMYCOSIS

DEFINITION: Chronic and rare infection of the nose and adjacent areas, involving fungi members of the phylum Zygomycota and order Entomophthorales. Most cases have occurred in Central and West Africa, Brazil, Colombia and Caribbean, mainly in healthy adults.

ETIOLOGY: Conidiobolus coronatus is the etiologic agent.

PATHOGENESIS: Infection by C. coranatus results from direct implantation of spores on nasal mucosa. Local trauma can facilitate the implantation that probably starts in the turbinates inferior and extends, slowly or sometimes rapidly, to ostia, foramina, paranasal sinuses, oropharynx and palate.

ORAL MANIFESTATION: Large erythematous infiltrated and progressive plaques occur mainly on the palate.

ASSOCIATED FINDINGS: Usually bilateral or less frequently unilateral distortion of the subcutaneous tissue of the nasal region, associated with a mucoid discharge and nasal obstruction.

MICROSCOPIC FINDINGS: Histopathology shows pyogranulomatous inflammatory reaction in the tissue with hyphae sparsely septate with an eosinophilic halo (Splendore-Hoeppli phenomenon) surrounding them.

DIAGNOSIS: The diagnosis is made through the clinical sings, the histopathologic appearance and laboratory identification of the fungus.

DIFFERENTIAL DIAGNOSIS: Differentiation is mainly with lymphatic edema and subcutaneous malignant lymphoma.

TREATMENT: Some lesions have spontaneous cure or following surgery. Lesions usually respond to oral treatment with potassium iodide (forty to sixty drops of saturated potassium iodide three times a day for three to four months). Amphotericin B (1mg/kg/day), clotrimoxazole, ketoconazole and itraconazole can also be used.

Fig1. Entomophthoromycosis - Bilateral distortion of the nasal region. Courtesy of Valdir Bandeira, MD, Recife, Brazil.
Fig2. Entomophthoromycosis - Erythematous infiltrated plaque on the palate. Courtesy of Valdir Bandeira, MD, Recife, Brazil.
Fig3. Entomophthoromycosis. Erythematous infiltrated plaque on the palate. Courtesy of Valdir Bandeira, MD, Recife, Brazil.
Fig4. Entomophthoromycosis. Hypha sparsely septate an eosinophilic halo.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:159.
2. Harman R. Subcutaneous zygomycosis. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:85-7.
3. Hay RJ, Roberts SOB, MacKenzie DWR. Mycology. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1127-216.
4. Kwon-Chung KJ, Bennett JE. Medical Mycology. Malvern:Lea & Febiger, 1992:447-63.
5. Lacaz CS, Porto C, Martins JEC. Micologia médica. 8ed. São Paulo:Sarvier, 1991:355-70.
6. Restrepo A. Treatment of tropical mycoses. J Am Acad Dermatol 1994;31(3 Pt 2):Suppl.91-102.
7. Rippon JW. Medical Mycology. 3ed. Philadelphia:W.B. Saunders, 1988:681-713.
8. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:343-58.
Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:102.

LARVA MIGRANS
CREEPING ERUPTION

DEFINITION: Larva migrans is characterized by itchy serpiginous tracks that primarily affect the feet, hands or buttocks and rarely the mouth. It is common on tropical countries.

ETIOLOGY: Larva migrans is caused by larvae from hookworms of various animals, mainly dogs and cats. The nematode Ancilostoma braziliense is the main etiologic agent. Other larvae can cause the disease, such as: A. caninum, A. ceylonicum, Uncinaria stenocephala, etc.

PATHOGENESIS: Adult hookworms live mainly in the intestines of animals and release ova into the feces. Ova are thus found in sand or soil contaminated by animals and, under favorable conditions of temperature and humidity, hatch into non-infectious rhabdoid larvae that later become filariform infective larvae. They are found in the upper half inch of the sand or soil.

The mouth infection, as the skin one, probably occurs by direct contact with contaminated sands, but the ingestion of contaminated food may also be responsible.

ORAL MANIFESTATION: Larva migrans is rare in the mouth, but when it happens it can involve the tongue, lips, cheeks, floor of the mouth, palate and oropharynx. The symptoms are itch and burn. Clinical examination shows erythematous areas and tortuous whitish lines. Many larvae may be active, producing bizarre patterns. Larvae move a few millimeters to a few centimeters each day.

ASSOCIATED FINDINGS: It may be associated to cutaneous larva migrans.

MICROSCOPIC FINDINGS: Circular or ovoid structures, compatible with nematode larva can be found inside cavities of subepithelial regions of the mouth.

DIAGNOSIS: Diagnosis is mainly clinical.

TREATMENT: Broad spectrum antihelminthic such as thiabendazole: 5 to 50 mg/kg for two to four days and rarely longer, and albendazole: 400mg daily for one to three days can be used with success and topical thiabendazole as 15% cream is also effective in cutaneous larva migrans.

Fig1. Larva migrans - Erythematous areas and tortuous whitish lines on the cheek. Courtesy of Oslei Paes de Almeida, PhD, Piracicaba, Brazil.
Fig2. Larva migrans - Erythematous areas and tortuous whitish lines on the palate. Courtesy of Oslei Paes de Almeida, PhD, Piracicaba, Brazil.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:169-70.
2. Burns DA. Diseases caused by arthropods and other noxious animals. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1265-324.
3. Canizares O. Larva migrans. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:332-4.
4. Farah FS, Klaus SN, Frankenberg S, Klion AD, Nutman TB. Protozoan and helminth infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2769-87.
5. Lopes MA, Zaia AA, de Almeida, OP, Scully C. Larva migrans that affect the mouth. Oral Surg Oral Med Oral Pathol 1994;77:362-7.
6. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:373-88.
7. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:115-6.

CERVICOFACIAL ACTINOMYCOSIS

DEFINITION: Chronic suppurative and granulomatous disease is characterized by peripheral spread and formation of multiple fraining sinus tracts. Theses sinuses drain from suppurative pyogenic lesions and the exsudate contains firm, lobulated grains or microcolonies of the etiologic agent.

ETIOLOGY: Members of the family Actinomycetaceae, called higher bacteria, a group that consist of commensals, is found in oral cavity and other mucosal areas.

Actinomyces israelli is the predominant organism in human infections.

PATHOGENESIS: The organism penetrates through trauma in mucous membrane of the mouth, by way of carious teeth. Salivary glands are sometimes involved.

ORAL MANIFESTATIONS: The most common initial symptoms are pain and swelling. Primary lesion is usually in the mandible or maxilla and probably arises as a direct extension from a periodontal abscess formed in turn as the result of carious teeth, dental extraction or trauma to the jaw.

ASSOCIATED FINDINGS: Dull red indurated nodule on the cheek or submaxillary region may be associated and multiple sinuses, discharging purulent material containing sulphur granules, may close temporarily and reopen later.

MICROSCOPIC FINDINGS: Microscopy reveals an acute pyogenic response, which evolves into a chronic granulomatous lesion, suppuration, and abscess formation. Granules have an adherent mass of polymorphonuclear neutrophils that are attached to radially arranged eosinophilic "clubs".

DIAGNOSIS: Diagnosis is made through the clinical signs and symptoms, laboratory examination, direct and culture methods, and histopathologic appearance, depending on the demonstration of organisms.

DIFFERENTIAL DIAGNOSIS: Cervicofacial actinomycosis must be differentiated from a number of chronic infections and neoplastic diseases.

TREATMENT: Penicillin is considered the treatment of choice. Regimens vary from 1 to 6 million units to 10 to 20 million units of intravenous penicillin G per day, depending on the severity of disease. Therapy is administered for thirty to forty five days prior to surgical incision, drainage, or excision, or the lesions are allowed to heal by secondary intention.

Fig1. Cervicofacial Actinomycosis - Red indurated nodule on the submaxillary region. Courtesy of Ivo Bussoloti Filho, MD, São Paulo, Brazil.
Fig2. Cervicofacial Actinomycosis - Lesion arises as a direct extension from a periodontal abscess. Courtesy of Ivo Bussoloti Filho, MD, São Paulo, Brazil.
Fig3. Cervicofacial Actinomycosis - Granule - Adherent mass of polymorphonuclear neutrophils attached to radially arranged eosinophilic "clubs". Hematoxylin and eosin stain.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:157-9.
2. Hay RJ, Roberts SOB, MacKenzie DWR. Mycology. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1127-216.
3. Kwon-Chung KJ, Bennett JE. Medical Mycology. Malvern:Lea & Febiger, 1992:560-93.
4. Lacaz CS, Porto C, Martins JEC. Micologia médica. 8ed. São Paulo:Sarvier, 1991:59-84.
5. Padilha-Gonçalves A, Canizares O, Hay R, Harman R. Actinomycosis. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:99-101.
6. Parish LC, Witkowski JA, Vassileva S. Color Atlas of Cutaneous Infections. Turin:Blackwell Science, 1995:145-6.
7. Rippon JW. Medical Mycology. 3ed. Philadelphia:W.B. Saunders, 1988:30-52.
8. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:343-58.
9. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:92-3.
10. Shadomy HJ, Utz JP. Deep fungal infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2468-97.

HISTOPLASMOSIS CAPSULATUM

DEFINITION: Histoplasmosis is a deep fungal infection with worldwide distribution.

ETIOLOGY: Histoplasmosis is caused by Histoplasma capsulatum var. capsulatum, a dimorphic fungus found in soil or in excrement of chickens, starlings, blackbirds, pigeon and bats.

PATHOGENESIS: Infection is initiated after inhalation of spores and results in a variety of clinical manifestation. Approximately 95 per cent of cases are subclinical. The remaining patients may have a chronic progressive lung disease, a chronic cutaneous or systemic disease, or an acute fatal systemic infection.

ORAL MANIFESTATION: Histoplasmosis can occur mainly in the mouth of patients infected with HIV. Mucous lesion includes painful ulcers, nodules, vegetating and necrotic lesions.

ASSOCIATED FINDINGS: In the skin lesions resemble molluscum contagiosum, erythematosus macules, necrotic papules and nodules.

MICROSCOPIC FINDINGS: Yeast cells within histiocytes have an uniform size and are visible in Gram, Giemsa, Wright's or hematoxylin and eosin stained smears. They resemble Leishmania donovani but lack the kinetoplast.

DIAGNOSIS: Clinical signs, histopathologic appearance and laboratory identification of the fungus make the diagnosis.

DIFFERENTIAL DIAGNOSIS: Lesions may resemble cryptococcosis, leishmaniasis, lymphomas and even sarcoidosis.

TREATMENT: Intravenous amphotericin B, 0,5 to 0,6 mg/kg in a daily dosage during acute stage, and then oral itraconazole 200 to 400 mg weekly are used.

Fig1. Histoplasmosis. Ulcer and necrotic lesion on the tongue before treatment.
Fig2. Histoplasmosis. Same patient after treatment.
Fig3. Histoplasmosis. Yeast cells within histiocytes. Hematoxylin and eosin stain.

SUGGESTED READINGS
1. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:157.
2. Hay R. Histoplasmosis. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:97-9.
3. Hay RJ, Roberts SOB, MacKenzie DWR. Mycology. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1127-216.
4. Kwon-Chung KJ, Bennett JE. Medical Mycology. Malvern:Lea & Febiger, 1992:464-513.
5. Lacaz CS, Porto E, Martins JEC. Micologia médica. 8ed. São Paulo:Sarvier, 1991:327-39.
6. Laskaris G. Color Atlas of Oral Diseases. Stuttgart:Georg Thieme Verlag, 1988:144-5.
7. Parish LC, Witkowski JA, Vassileva S. Color Atlas of Cutaneous Infections. Turin:Blackwell Science, 1995:140-1.
8. Rippon JW. Medical Mycology. 3ed. Philadelphia:W.B. Saunders, 1988:381-423.
9. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:343-58.
10. Shadomy HJ, Utz JP. Deep fungal infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2468-97.
11. Swindells S, Dureham T, Johansson SL et al. Oral histoplasmosis in a patient infected with HIV. A case report. Oral Surg Oral Med Oral Pathol 1994;77:126-30.

CUTANEOUS TUBERCULOSIS

DEFINITION: Tuberculosis of the skin is a spectrum of skin condition due to infection with obligatory mycobacterial pathogens. Orificial tuberculosis and papulonecrotic tuberculid can occur in the mouth.

ETIOLOGY: Etiologic agents are Mycobacterium tuberculosis, M. bovis, and, under certain conditions, bacillus Calmette-Guérin (BCG), an attenuated strain of M. bovis.

PATHOGENESIS: Infection may be exogenous (from an outside source), it may occur after autoinoculation (orificial tuberculosis) or it may be endogenous (continuous extension of a tuberculosis process, by way of the lymphatics or by hematogenous dissemination).

Some conditions represent recurrent disseminated or systemic skin reactions to toxins of tubercle bacilli: the tuberculids.

ORAL MANIFESTATION: There are two types that may occur in the mouth: orificial tuberculosis characterized by circular or irregular ulcer which floor is often covered by pseudomembranous material, and papulonecrotic tuberculid showing red, symptomless papules that develops a central necrosis and result in red pitted scars.

ASSOCIATED FINDINGS: Cavitary pulmonar tuberculosis, ulcerative tuberculosis of the pharynx and larynx are frequently associated with oral lesions. Papulonecrotic tuberculid, characterized by papules and pitted scars on the knees, elbows, buttocks and lower trunk are also associated.

MICROSCOPIC FINDINGS: Orificial tuberculosis shows tubercles with caseation may be found deep in dermis and papulonecrotic tuberculid, necrosis of upper dermis and inflammatory tuberculoid infiltrate surrounding the necrotic area. Obliterative or granulomatous vasculitis of blood vessels may also be present.

DIAGNOSIS: Diagnosis of orificial tuberculosis is made by the finding of painful ulcers inside the mouth in patients with pulmonary tuberculosis, presence of acid-fast organisms and positive culture. Papulonecrotic tuberculid is diagnosed by the clinical picture and histopathology.

DIFFERENTIAL DIAGNOSIS: Orificial tuberculosis must be differentiated from syphilitic lesions, aphthous ulcers and carcinomas, and papulonecrotic tuberculid from pityriasis lichenoides et varioliformis acuta.

TREATMENT: Triple chemotherapy is used with isoniazid (5-10 mg/kg/day up to 300 mg/day), rifampicin (10-20 mg/kg/day up to 600 mg) and ethambutol (15-25 mg/kg/day), for six months.

Fig1. Orificial Tuberculosis - Irregular ulcer covered by pseudomembranous material on the cheek. Courtesy of Ivo Bussoloti Filho, MD, São Paulo, Brazil.
Fig2. Orificial Tuberculosis - Irregular ulcer covered by pseudomembranous material on the palate. Courtesy of Ivo Bussoloti Filho, MD, São Paulo, Brazil.
Fig3. Papulonecrotic tuberculid - Red papules with central necrosis and red pitted scars. Courtesy of Iphis Campbell, MD, Brasília, Brazil.
Fig4. Orificial Tuberculosis - Tubercles with caseation in deep dermis.

SUGGESTED READINGS
1. Adriaans B, Dominguez-Soto L, Canizares O, Harman R. Tuberculosis of the skin. In: Canizares O, Harman R. Clinical Tropical Dermatology. 2ed. Boston:Blackwell Scientific, 1992:201-15.
2. Azulay RD. Dermatologia. Rio de Janeiro:Guanabara Koogan, 1985:132-5.
3. Laskaris G. Color Atlas of Oral Diseases. Stuttgart:Georg Thieme Verlag, 1988:132-4.
4. Parish LC, Witkowski JA, Vassileva S. Color Atlas of Cutaneous Infections. Turin:Blackwell Science, 1995:43-6.
5. Sampaio SAP, Castro RM, Rivitti EA. Dermatologia Básica. 4ed. São Paulo:Artes Médicas, 1989:287-310.
6. Savin JA. Mycobacterial infections. In: Champion RH, Burton JL, Ebling FJG. eds. Rook, Wilkinson, Ebling Textbook of Dermatology. 5ed. Londres:Blackwell Scientific, 1992:1033-63.
7. Schaller KF. ed. Color Atlas of Tropical Dermatology and Venereology. Berlin:Springer-Verlag, 1994:37-8.
8. Sehgal VN, Bhattacharya SN, Jain S, Loganik K. Cutaneous tuberculosis: the evolving scenario. Int J Dermatol 1994; 33:97-104.
9. Tappeiner G, Wolff K. Tuberculosis and other mycobacterial infections. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg JM, Austen KF. Dermatology in General Medicine. 4ed. New York:McGraw-Hill, 1993:2370-95.