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Genital erosions and ulcers in childhood and adolescence
J Pediatr Adolesc Gynecol (2004) 17:151–153
Tips for Clinicians Genital Erosions and Ulcers in Childhood and Adolescence Editor: Cynthia Holland-Hall, MD Author: Deborah Bartholomew, MD Department of Obstetrics and Gynecology, The Ohio State University College of Medicine and Public Health, Columbus, Ohio, USA
Introduction Genital erosions and ulcers in children and adolescents present a complex diagnostic dilemma. Most lesions are exquisitely painful and result in considerable anxiety and emotional distress for both the patient and family, not to mention the physician’s frustration in trying to expediently diagnose and treat a lesion which is rarely seen in general practice. The differential is vast and may have serious medical implications.1 A basic approach to the evaluation of genital ulcers and erosions is presented along with treatment options. First, a few basic definitions are needed. Erosions involve focal loss of the epidermis, whereas ulcers are deep and extend into the dermis. Secondary infection can occur with any loss of mucosal or skin integrity, further confusing the clinical presentation. Examples of erosions include genital herpes, lichen sclerosus, and candidiasis. Ulcers include genital apthae and fixed drug eruptions. Taking a History A detailed history is essential. The evolution of the lesion is important information to obtain. Did the lesion start as a vesicle and progress to a pustule? Are there any associated skin or oral lesions? Is the lesion recurrent or an isolated event? Does the patient complain of tender groin nodes or have a vaginal discharge? A sensitive inquiry about sexual activity is key. It is helpful to interview the patient in private, stressing the importance of disclosure to help direct therapy. Assure the patient of confidentiality. Adolescents frequently equate sexual activity with penile vaginal Address correspondence to: Deborah Bartholomew, MD, The Ohio State University College of Medicine and Public Health, 516 Means Hall, 1654 Upham Dr., Columbus, OH 43210.
쑖 2004 North American Society for Pediatric and Adolescent Gynecology Published by Elsevier Inc.
penetration and dismiss other forms of sexual expression. Inoculation of infectious agents can occur through digital and oral genital contact. The possibility of abuse must always be considered. All medications, including over the counter remedies, must be disclosed.
Physical Examination Physical examination of the external genitalia can be accomplished in the frog leg or knee chest position. Gentle lateral labial traction allows visualization of the vestibule and the vaginal introitus. Keep in mind that by the time the lesion is examined, considerable healing may already have occurred. Significant erosions may be present secondary to scratching pruritic lesions. Discharge should be collected for microscopy and culture. If fungal infection is suspected, the lesion can be scraped with a 15 blade and a KOH prep made for microscopy. Fungal cultures are helpful if the KOH microscopy exam is negative. Although some lesions are easily diagnosed by visual inspection, most require further testing, even a biopsy, as there is considerable overlap in their clinical appearance (Table 1).
Causes of Genital Erosions and Ulcers An infectious etiology should not be excluded based on history alone. Genital herpes is the most common cause of genital erosions. Classic primary herpes with associated adenopathy and multiple vesicles progressing to pustules over 10–14 days is easy to diagnose. Recurrent genital herpes may be subtle and elusive, lasting only 5–7 days. If the lesion has progressed from the vesicular to the pustular stage, the culture may be negative. Take the sample from the base of the lesion, unroofing any crust. If direct immunofluorescence is available, the sample can be smeared on 1083-3188/04/$22.00 doi:10.1016/j.jpag.2004.01.010
152
Bartholomew: Genital Erosions and Ulcers in Childhood and Adolescence
Table 1. Laboratory Evaluation KOH prep of discharge or lesion Yeast culture, if KOH negative Hemophilus ducreyi culture Herpes culture HSV-1, HSV-2, IgG, IgM RPR ANA Monospot and/or EBV titers HIV Biopsy
a glass slide. DNA studies and direct immunofluorescence are sensitive and yield rapid results. A simple Pap smear of the lesion, although not the most sensitive test, can give an immediate answer if the classic multinuclear giant cells are seen. The decision to do type specific serologic testing with IgG and IgM titers is based on clinical suspicion, realizing that it is not uncommon to have immunity to herpes simplex type I, due to the general prevalence of the virus. In the setting of immunosuppression, the lesions last longer, and are more extensive and necrotic. Shingles or herpes zoster can also occur in the immunosuppressed population. The distinction is easy in that the lesions follow a dermatome and are unilateral. Treatment with antivirals, such as acyclovir and valacyclovir, can decrease the duration and severity of both genital herpes and shingles. If syphilis is in the differential, realize that serum serological tests may be negative at presentation of the initial lesion. The firm, indurated, painless ulcer usually lasts 6–8 weeks with a positive Rapid Plasma Reagin (RPR) test developing within 2 weeks. The fluorescent treponema antibody absorption test is very specific and is more likely to be positive early. If available, dark-field microscopy can be used to identify the causative organism in the ulcer before serologic tests become positive. Although rare in the United States, chancroid is increasing in incidence. The ulcer is exquisitely painful and is associated with suppurative inguinal adenopathy. In contrast to the ulcer of syphilis, induration is absent. Culture for Haemophilus ducreyi is possible on selective media and it is important to inform the lab to look for this organism. Candidal infections confined to the vulvar skin may not be associated with discharge, but classically have satellite lesions at the edge. A sore throat may suggest concomitant oral ulcers or mononucleosis. Self limited genital ulcers have been associated with Epstein Barr Virus (EBV) infection.2 Keep in mind when evaluating for this infection, however, that the monospot heterophile antibody test may not be reliable in preschool-age children; EBV titers are the more appropriate serologic test to use in this population.
Associated symptoms of headache, photophobia, arthralgia, fever, and myalgia may suggest multisystem disease and an underlying vasculitis. Lupus can be associated with idiopathic genital ulcers. Any chronic medical condition or use of immune suppressant medication increases the likelihood of secondary infection. Fixed drug eruptions can involve the genitalia and some of the offending medications are commonly used, such as ibuprofen (Table 2). Ulcers are recurrent, in the same location, each time the drug is ingested. Mild prodromal symptoms often accompany genital ulcers or may be the reason for the initial drug ingestion. Erosive lichen sclerosus of the genitalia may result in considerable scarring, agglutination, and loss of the labia minora.3 Anterior agglutination of the labia may bury the clitoris and urethra, with pooling of urine in the vagina. Excoriation and erosion of the genitalia result from chronic scratching secondary to recalcitrant pruritus. It can be so severe as to suggest sexual abuse. Secondary infection with bacteria and yeast may further complicate the presentation. The classic symmetrical white hourglass lesion has a peculiar sheen similar to parchment paper. If the appearance is classic, biopsy can be avoided and treatment initiated with an ultrapotent, Class I or II steroid ointment.4 If there is any question as to the diagnosis, a small 3 mm punch biopsy is necessary. Pretreatment with 5% lidocaine cream and use of a 30 gauge needle for injection allows a painless biopsy. The key to use of ultrapotent steroid ointment is to use it sparingly. A thin layer is applied to the genitalia with care to avoid the genitocrural folds and anus. It can be applied daily and requires frequent reassessment to avoid overuse and resultant atrophy. It is helpful to dispense only a 15 g tube at a time. Once the symptoms are controlled, the frequency can be decreased to once or twice a week. The therapy can be stopped provided that close surveillance continues with prompt initiation of therapy for recurrent symptoms. The goal is to normalize the skin texture and control the pruritus. Scarring and architectural loss may be permanent. Surgical separation of fused labia can only be accomplished after the disease is under control. It is a fallacy that puberty cures the disease. Table 2. Medications Causing Fixed Drug Eruptions Nonsteriodal anti-inflammatory drugs Metronidazole Acetaminophen Sulfonamides Tetracycline Phenytoin Oral contraceptives Barbiturates Phenolphthalein
Bartholomew: Genital Erosions and Ulcers in Childhood and Adolescence
Unfortunately, there is no cure, but control can easily be achieved. Apthous genital ulcers are deep painful lesions that occur suddenly, last for weeks and heal with scarring. If genital ulcers are associated with oral canker sores, then Behc¸et’s disease must be considered. To diagnose this multisystem vascular disease, a triad of genital and oral ulcers with an associated uveitis must be present. The criteria for diagnosis have been revised to include oral ulcers associated with two other criteria, which may include genital ulcers.5 Examples of vasculitis involving other areas include genital ulcers, cerebritis, retinitis, uveitis, colitis, and erythema nodosum, to name a few. The extent of the work-up is dependent on the symptomatology. The vast majority of Behc¸et’s cases occur in patients of Mediterranean, Middle Eastern, or Asian descent and probably represent a genetic alteration in immunity. Biopsy of the ulcer reveals a necrotizing arteritis, which is diagnostic. Most of the cases that are seen in practice are isolated genital apthae and are called apthous minor. Ulcers involving the oral and genital mucosa without evidence of vasculitis involving other organ systems are called apthous major. Treatment consists of prompt use of systemic steroids early in the course and then tapering off as the lesions heal. Topical ultrapotent steroid ointment can be used for milder cases. If recurrences are frequent, treatment with other medications including azathioprine, dapsone, cyclosporine, methotrexate, or hydroxychloroquine sulfate may be necessary. Other causes of aphthous ulcers include pyoderma gangrenosum, fixed drug eruptions, mononucleosis and lupus. Recurrent deep, necrotic genital ulcers can also occur in patients with human immunodeficiency virus and are not necessarily due to herpes virus, but rather represent severe apthous ulcers. Although uncommon, vulvar manifestations of Crohn’s disease may precede the gastrointestinal symptoms. Cicatricial and, rarely, bullous pemphigoid can present in childhood and may mimic lichen sclerosus with extensive scarring.6 Biopsy of the adjacent normal skin surrounding the lesion must be transported in saline for diagnostic immunofluorescent studies. Bullous erosive diseases such as erythema multiforme and toxic epidermal necrolysis involve mucous membranes including the vagina and the vulva.7 This area is frequently overlooked and not treated. Extensive scarring can result with obliteration of the vagina. It is important to keep the labia separated and to prevent coaptation of the vaginal walls. Application of zinc oxide externally and daily insertion of a plastic tampon applicator coated with steroid ointment is all that is needed to prevent scarring.
153
Table 3. General Treatment Guidelines Remove all irritants No pads, underwear, tight clothes Sitz baths with warm water, 15 min, qid, and pat dry or cool hair dryer Domeboro compresses 1 packet/500ml water Petrolatum or zinc oxide barrier after soak Analgesics Oral fluconazole for secondary yeast Cefadroxil for secondary bacterial infection Catheterize, if necessary
Treatment Principles Therapy for genital erosions and ulcers is directed at pain relief, general supportive care, prevention of scarring, and specific treatment based on the diagnosis (Table 3). Some of the conditions are chronic, such as lichen sclerosus, but can be controlled with improvement in the quality of life. Others are self limited or easily treated once an appropriate diagnosis is obtained. A methodical approach to evaluation will allow appropriate diagnosis and therapy. Further information regarding diagnosis and management of vulvar erosions and ulcers can be obtained from our colleagues in dermatology.8,9
References 1. Rosen T, Brown TJ: Genital ulcers. Evaluation and treatment. Dermatol Clin 1998; 16:673 2. Taylow S, Drake SM, Dedicoat M, et al: Genital ulcers associated with acute Epstein-Barr virus infection. Sex Transm Infect 1998; 74:296 3. Powell J, Wojnarowska F: Childhood vulvar lichen sclerosus: An increasingly common problem. J Am Acad Dermatol 2001; 44:803 4. Garzon MC, Paller AS: Ultrapotent topical corticosteroid treatment of childhood genital lichen sclerosus. Arch Dermatol 1999; 135:525 5. International Study Group for Behc¸et’s Disease: Criteria for the diagnosis of Behc¸et’s disease. Lancet 1990; 335:1078 6. Farrell AM, Kirtschig G, Dalziel K, et al: Childhood vulval pemphigoid: a clinical and immunopathological study of 5 patients. Br J Dermatol 1999; 140:308 7. Marren P, Wojnarowska F, Venning V, et al: Vulvar involvement in autoimmune bullous diseases. J Reprod Med 1993; 38:101 8. McKay M: Differential diagnosis of the vulvar ulcer. In: Obstetric and Gynecologic Dermatology, (2nd ed.). Edited by M Black, M McKay. London, Mosby International, 2002, pp 187–207 9. Margesson LJ: Inflammatory diseases of the vulva. In: Genital Skin DisordersEdited by BJ Fisher, LJ Margesson. St. Louis, MO, Mosby, 1998, pp 154–176
Tips for Clinicians Genital Erosions and Ulcers in Childhood and Adolescence Editor: Cynthia Holland-Hall, MD Author: Deborah Bartholomew, MD Department of Obstetrics and Gynecology, The Ohio State University College of Medicine and Public Health, Columbus, Ohio, USA
Introduction Genital erosions and ulcers in children and adolescents present a complex diagnostic dilemma. Most lesions are exquisitely painful and result in considerable anxiety and emotional distress for both the patient and family, not to mention the physician’s frustration in trying to expediently diagnose and treat a lesion which is rarely seen in general practice. The differential is vast and may have serious medical implications.1 A basic approach to the evaluation of genital ulcers and erosions is presented along with treatment options. First, a few basic definitions are needed. Erosions involve focal loss of the epidermis, whereas ulcers are deep and extend into the dermis. Secondary infection can occur with any loss of mucosal or skin integrity, further confusing the clinical presentation. Examples of erosions include genital herpes, lichen sclerosus, and candidiasis. Ulcers include genital apthae and fixed drug eruptions. Taking a History A detailed history is essential. The evolution of the lesion is important information to obtain. Did the lesion start as a vesicle and progress to a pustule? Are there any associated skin or oral lesions? Is the lesion recurrent or an isolated event? Does the patient complain of tender groin nodes or have a vaginal discharge? A sensitive inquiry about sexual activity is key. It is helpful to interview the patient in private, stressing the importance of disclosure to help direct therapy. Assure the patient of confidentiality. Adolescents frequently equate sexual activity with penile vaginal Address correspondence to: Deborah Bartholomew, MD, The Ohio State University College of Medicine and Public Health, 516 Means Hall, 1654 Upham Dr., Columbus, OH 43210.
쑖 2004 North American Society for Pediatric and Adolescent Gynecology Published by Elsevier Inc.
penetration and dismiss other forms of sexual expression. Inoculation of infectious agents can occur through digital and oral genital contact. The possibility of abuse must always be considered. All medications, including over the counter remedies, must be disclosed.
Physical Examination Physical examination of the external genitalia can be accomplished in the frog leg or knee chest position. Gentle lateral labial traction allows visualization of the vestibule and the vaginal introitus. Keep in mind that by the time the lesion is examined, considerable healing may already have occurred. Significant erosions may be present secondary to scratching pruritic lesions. Discharge should be collected for microscopy and culture. If fungal infection is suspected, the lesion can be scraped with a 15 blade and a KOH prep made for microscopy. Fungal cultures are helpful if the KOH microscopy exam is negative. Although some lesions are easily diagnosed by visual inspection, most require further testing, even a biopsy, as there is considerable overlap in their clinical appearance (Table 1).
Causes of Genital Erosions and Ulcers An infectious etiology should not be excluded based on history alone. Genital herpes is the most common cause of genital erosions. Classic primary herpes with associated adenopathy and multiple vesicles progressing to pustules over 10–14 days is easy to diagnose. Recurrent genital herpes may be subtle and elusive, lasting only 5–7 days. If the lesion has progressed from the vesicular to the pustular stage, the culture may be negative. Take the sample from the base of the lesion, unroofing any crust. If direct immunofluorescence is available, the sample can be smeared on 1083-3188/04/$22.00 doi:10.1016/j.jpag.2004.01.010
152
Bartholomew: Genital Erosions and Ulcers in Childhood and Adolescence
Table 1. Laboratory Evaluation KOH prep of discharge or lesion Yeast culture, if KOH negative Hemophilus ducreyi culture Herpes culture HSV-1, HSV-2, IgG, IgM RPR ANA Monospot and/or EBV titers HIV Biopsy
a glass slide. DNA studies and direct immunofluorescence are sensitive and yield rapid results. A simple Pap smear of the lesion, although not the most sensitive test, can give an immediate answer if the classic multinuclear giant cells are seen. The decision to do type specific serologic testing with IgG and IgM titers is based on clinical suspicion, realizing that it is not uncommon to have immunity to herpes simplex type I, due to the general prevalence of the virus. In the setting of immunosuppression, the lesions last longer, and are more extensive and necrotic. Shingles or herpes zoster can also occur in the immunosuppressed population. The distinction is easy in that the lesions follow a dermatome and are unilateral. Treatment with antivirals, such as acyclovir and valacyclovir, can decrease the duration and severity of both genital herpes and shingles. If syphilis is in the differential, realize that serum serological tests may be negative at presentation of the initial lesion. The firm, indurated, painless ulcer usually lasts 6–8 weeks with a positive Rapid Plasma Reagin (RPR) test developing within 2 weeks. The fluorescent treponema antibody absorption test is very specific and is more likely to be positive early. If available, dark-field microscopy can be used to identify the causative organism in the ulcer before serologic tests become positive. Although rare in the United States, chancroid is increasing in incidence. The ulcer is exquisitely painful and is associated with suppurative inguinal adenopathy. In contrast to the ulcer of syphilis, induration is absent. Culture for Haemophilus ducreyi is possible on selective media and it is important to inform the lab to look for this organism. Candidal infections confined to the vulvar skin may not be associated with discharge, but classically have satellite lesions at the edge. A sore throat may suggest concomitant oral ulcers or mononucleosis. Self limited genital ulcers have been associated with Epstein Barr Virus (EBV) infection.2 Keep in mind when evaluating for this infection, however, that the monospot heterophile antibody test may not be reliable in preschool-age children; EBV titers are the more appropriate serologic test to use in this population.
Associated symptoms of headache, photophobia, arthralgia, fever, and myalgia may suggest multisystem disease and an underlying vasculitis. Lupus can be associated with idiopathic genital ulcers. Any chronic medical condition or use of immune suppressant medication increases the likelihood of secondary infection. Fixed drug eruptions can involve the genitalia and some of the offending medications are commonly used, such as ibuprofen (Table 2). Ulcers are recurrent, in the same location, each time the drug is ingested. Mild prodromal symptoms often accompany genital ulcers or may be the reason for the initial drug ingestion. Erosive lichen sclerosus of the genitalia may result in considerable scarring, agglutination, and loss of the labia minora.3 Anterior agglutination of the labia may bury the clitoris and urethra, with pooling of urine in the vagina. Excoriation and erosion of the genitalia result from chronic scratching secondary to recalcitrant pruritus. It can be so severe as to suggest sexual abuse. Secondary infection with bacteria and yeast may further complicate the presentation. The classic symmetrical white hourglass lesion has a peculiar sheen similar to parchment paper. If the appearance is classic, biopsy can be avoided and treatment initiated with an ultrapotent, Class I or II steroid ointment.4 If there is any question as to the diagnosis, a small 3 mm punch biopsy is necessary. Pretreatment with 5% lidocaine cream and use of a 30 gauge needle for injection allows a painless biopsy. The key to use of ultrapotent steroid ointment is to use it sparingly. A thin layer is applied to the genitalia with care to avoid the genitocrural folds and anus. It can be applied daily and requires frequent reassessment to avoid overuse and resultant atrophy. It is helpful to dispense only a 15 g tube at a time. Once the symptoms are controlled, the frequency can be decreased to once or twice a week. The therapy can be stopped provided that close surveillance continues with prompt initiation of therapy for recurrent symptoms. The goal is to normalize the skin texture and control the pruritus. Scarring and architectural loss may be permanent. Surgical separation of fused labia can only be accomplished after the disease is under control. It is a fallacy that puberty cures the disease. Table 2. Medications Causing Fixed Drug Eruptions Nonsteriodal anti-inflammatory drugs Metronidazole Acetaminophen Sulfonamides Tetracycline Phenytoin Oral contraceptives Barbiturates Phenolphthalein
Bartholomew: Genital Erosions and Ulcers in Childhood and Adolescence
Unfortunately, there is no cure, but control can easily be achieved. Apthous genital ulcers are deep painful lesions that occur suddenly, last for weeks and heal with scarring. If genital ulcers are associated with oral canker sores, then Behc¸et’s disease must be considered. To diagnose this multisystem vascular disease, a triad of genital and oral ulcers with an associated uveitis must be present. The criteria for diagnosis have been revised to include oral ulcers associated with two other criteria, which may include genital ulcers.5 Examples of vasculitis involving other areas include genital ulcers, cerebritis, retinitis, uveitis, colitis, and erythema nodosum, to name a few. The extent of the work-up is dependent on the symptomatology. The vast majority of Behc¸et’s cases occur in patients of Mediterranean, Middle Eastern, or Asian descent and probably represent a genetic alteration in immunity. Biopsy of the ulcer reveals a necrotizing arteritis, which is diagnostic. Most of the cases that are seen in practice are isolated genital apthae and are called apthous minor. Ulcers involving the oral and genital mucosa without evidence of vasculitis involving other organ systems are called apthous major. Treatment consists of prompt use of systemic steroids early in the course and then tapering off as the lesions heal. Topical ultrapotent steroid ointment can be used for milder cases. If recurrences are frequent, treatment with other medications including azathioprine, dapsone, cyclosporine, methotrexate, or hydroxychloroquine sulfate may be necessary. Other causes of aphthous ulcers include pyoderma gangrenosum, fixed drug eruptions, mononucleosis and lupus. Recurrent deep, necrotic genital ulcers can also occur in patients with human immunodeficiency virus and are not necessarily due to herpes virus, but rather represent severe apthous ulcers. Although uncommon, vulvar manifestations of Crohn’s disease may precede the gastrointestinal symptoms. Cicatricial and, rarely, bullous pemphigoid can present in childhood and may mimic lichen sclerosus with extensive scarring.6 Biopsy of the adjacent normal skin surrounding the lesion must be transported in saline for diagnostic immunofluorescent studies. Bullous erosive diseases such as erythema multiforme and toxic epidermal necrolysis involve mucous membranes including the vagina and the vulva.7 This area is frequently overlooked and not treated. Extensive scarring can result with obliteration of the vagina. It is important to keep the labia separated and to prevent coaptation of the vaginal walls. Application of zinc oxide externally and daily insertion of a plastic tampon applicator coated with steroid ointment is all that is needed to prevent scarring.
153
Table 3. General Treatment Guidelines Remove all irritants No pads, underwear, tight clothes Sitz baths with warm water, 15 min, qid, and pat dry or cool hair dryer Domeboro compresses 1 packet/500ml water Petrolatum or zinc oxide barrier after soak Analgesics Oral fluconazole for secondary yeast Cefadroxil for secondary bacterial infection Catheterize, if necessary
Treatment Principles Therapy for genital erosions and ulcers is directed at pain relief, general supportive care, prevention of scarring, and specific treatment based on the diagnosis (Table 3). Some of the conditions are chronic, such as lichen sclerosus, but can be controlled with improvement in the quality of life. Others are self limited or easily treated once an appropriate diagnosis is obtained. A methodical approach to evaluation will allow appropriate diagnosis and therapy. Further information regarding diagnosis and management of vulvar erosions and ulcers can be obtained from our colleagues in dermatology.8,9
References 1. Rosen T, Brown TJ: Genital ulcers. Evaluation and treatment. Dermatol Clin 1998; 16:673 2. Taylow S, Drake SM, Dedicoat M, et al: Genital ulcers associated with acute Epstein-Barr virus infection. Sex Transm Infect 1998; 74:296 3. Powell J, Wojnarowska F: Childhood vulvar lichen sclerosus: An increasingly common problem. J Am Acad Dermatol 2001; 44:803 4. Garzon MC, Paller AS: Ultrapotent topical corticosteroid treatment of childhood genital lichen sclerosus. Arch Dermatol 1999; 135:525 5. International Study Group for Behc¸et’s Disease: Criteria for the diagnosis of Behc¸et’s disease. Lancet 1990; 335:1078 6. Farrell AM, Kirtschig G, Dalziel K, et al: Childhood vulval pemphigoid: a clinical and immunopathological study of 5 patients. Br J Dermatol 1999; 140:308 7. Marren P, Wojnarowska F, Venning V, et al: Vulvar involvement in autoimmune bullous diseases. J Reprod Med 1993; 38:101 8. McKay M: Differential diagnosis of the vulvar ulcer. In: Obstetric and Gynecologic Dermatology, (2nd ed.). Edited by M Black, M McKay. London, Mosby International, 2002, pp 187–207 9. Margesson LJ: Inflammatory diseases of the vulva. In: Genital Skin DisordersEdited by BJ Fisher, LJ Margesson. St. Louis, MO, Mosby, 1998, pp 154–176