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Adolescent Medicine
Case Scenario’s
RUBA RIZK, MD, FAAP
CONSULTANT, ADOLESCENT MEDICINE
AL JALILA CHILDREN’S SPECIALTY HOSPITAL
Objectives
Case 1:
Review approach to vulvar ulcers
Review detailed differential of vulvar ulcers
THE CASE OF THE
PERIMENARCHEAL GIRL WITH
RECURRENT VULVAR ULCERS
CASE 1
Case
12 yo F presents to the ER with “vaginal sores and fever” for the past 6 days
6 days ago developed fever to 102F with sore throat and oral “canker sores”
◦ Seen by PCP where RST done was Positive
◦ Prescribed cephalexin for 10 days
2 days later developed painful vulvar “sores” that progressively worsened
causing severe pain, discomfort, dysuria and inability to ambulate
Sent to ER by PCP
Case
Similar episode 6 weeks earlier where she developed sore throat, oral “canker
sores” and high fevers initially followed three days later by dysuria and vulvar
ulcers
At onset of sore throat she was seen by her pediatrician
◦ RST negative
◦ Sent home
Once vulvar ulcers developed went again to pediatrician
◦ Prescribed topical ABX and cephalexin PO for 10 days
◦ Culture of “sores” sent that grew E. coli and Salmonella species
She remained febrile for ~10 days but eventually fever, oral and vulvar ulcers all
resolved completely
Case
ROS: decreased appetite, +fever, no weight loss, no URI symptoms, +sore throat,
+dysuria, no frequency/hematuria, no diarrhea, no abdominal pain, no rash, no
joint pain, no vision changes/eye pain/redness
Menstrual history: Menarche 11.5 yrs, regular qMo x5d
PMH: recurrent “strep throat” and recurrent episodes of “canker sores” mostly
on her tongue about five times per year
Case
PSH: PET tubes at 11mo
FH: Ethnicity: Irish-American
◦ Parents healthy; PGM w hemolytic anemia
HEADDS
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Lives with her parents. Great relationship
Gifted student, 100% average; enjoys music and dancing
Denies sexual activity, denies sexual abuse or being inappropriately touched
Denies toxic habits
ED Course
Febrile
S/P Morphine
ID C/S
◦ Started on IV cephalexin
Admitted for pain management
Physical Exam: Pertinents
Oropharynx: diffuse glossitis with
superficial mucosal ulceration and
inflammation on exam of her
oropharynx. Pharyngeal erythema with
exudates
Neck: No LAD
External genitalia: marked swelling of
the vulva with deep ulcers, some
covered with black eschar, on the labia
and in the vagina with evidence of
necrosis
No rash
Thoughts?
CON CE R N S?
I N V ESTIGATIONS?
Labs
WBC:19,200 N:66% Bands: 13%
ESR: 65 mm/hr
CRP: 14.5 mg/dl
Throat culture: normal flora
Bacterial culture of the vulvar ulcers grew a few E. coli and moderate candida albicans with normal skin flora
Viral culture: negative
HSV, CMV, EBV, and HIV were negative or indicated remote infection
Gonorrhea and chlamydia negative
Lupus w/u was negative
Biopsy of ulcer: “ulcer with suppurative inflammation. PAS stain is negative for hyphae. Immunohistochemical studies show no
reactivity for herpes virus antigen and LMP (EBV-encoded membrane protein). In the context of the clinical findings, these
histopathologic features are compatible with the clinical impression of Behcet’s syndrome”
Hospital Course
Pain: continuous and bolus IV morphine via PCA
ABX: IV cefazolin and acyclovir
Topical betamethasone ointment & lidocaine gel to vulva
Day 1: GYN consulted, ID on board
Day 3: examination under anesthesia with biopsy of the vulvar ulcers was done; and Rheum C/S
Day 4: ENT C/S
Day 6: Adolescent Medicine C/S
Day 7: Opthalmology C/S
D8: Medrol Pack started, ABX dcd
D13: DC home
1 week follow up
No fever or pain
Taking no medications
Examination of oropharynx: normal with no lesions and moderately enlarged
(3+) tonsils without erythema or exudate
Examination of vulva: most of the ulcers had healed without scars; the largest
one had some granulation tissue but there was no tenderness or swelling
5 week follow up
3rd similar episode with throat pain, high fevers to 105F, and 3days later, vulvar
pain
Exam: enlarged hyperemic tonsils with bilateral exudates, no cervical
lymphadenopathy, and 2 ulcers covered with grayish eschar on the labia majora
at 3 o’clock and 7 o’clock around the vaginal introitus. +tender to touch
LAB: WBC: 12,500; ESR :45 mm/hr; and CRP: 2.4 mg/dl
TX: 7d methylprednisolone taper & augmentin 10 days
F/U 4d later: afebrile the past 3 days, denied pain in her throat or vulva. On
exam, pharyngitis resolved, one of the vulvar ulcers had no eschar and was
nearly healed and the other was much improved
Follow Up
Episodes of periodic fevers associated with aphthous stomatitis and pharyngitis > ?? a variant of PFAPA syndrome, referred to tonsillectomy
Tonsillectomy done 3mo after 3rd episode
2 weeks post-op developed fevers to 103F and, 2 days later, multiple painful oral
aphthous ulcers. NO vulvar ulcers or pain. On exam after 1 week of illness, >5
ulcers seen on buccal mucosa, tongue, and posterior pharynx and she had
tender anterior and posterior lymph nodes bilaterally
Treated her with a 7d methylprednisolone taper with quick resolution of the
stomatitis, adenitis, and fever
Follow up
19 months after the tonsillectomy she has had no further episodes of fever or
ulcers, either genital or oral
Vulvar Ulcers
Rare clinical presentation, especially in non-sexually-active perimenarcheal girls
Source of intense anxiety, pain, and sometimes shame
Painful genital ulcers are associated with sexually-transmitted herpes simplex
virus types I and II and this is often the first diagnosis that comes to the
clinician’s mind
Non-sexually transmitted causes of vulvar ulcers include
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Epstein-Barr virus (EBV)
Cytomegalovirus (CMV)
Drug reaction
Dermatologic and autoimmune conditions such as Behcets disease
Manifestation of a systemic illness such as Crohns disease
In sexually active adolescents, sexually transmitted infections are the usual
culprits and Herpes simplex virus is the usual suspect
Less common but well studied and understood
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Syphilis
Lymphogranuloma venereum (LGV)
Chancroid
HIV-associated ulcerations
Non-sexually transmitted infectious causes of vulvar ulcers are less understood
◦ Candida is very common however, in the presence of our patient’s associated symptoms
much less likely
◦ Epstein-Barr virus (EBV)
EBV
Common cause of non sexually transmitted vulvar ulcers
In a review of 26 cases reported in the literature, median age of onset was 14.5 years and the
majority of cases occurred in non-sexually active adolescents
Patients presented with symptoms of mononucleosis, including fever, fatigue and tonsillitis, with
associated painful genital ulcers as the dominating symptom of EBV infection
Diagnosis is usually made by serology showing IgM antibodies to EBV viral capsid antigens
Treatment is supportive based on symptoms
EBV is going unrecognized by many clinicians who falsely label these adolescents with the
diagnosis of HSV
Few cases of Cytomegalovirus (CMV) infection have also been reported in the literature as a
cause of vulvar ulceration in immunocompetent patients
Behcet’s Disease
A complex multisystem disease characterized by mucocutaneous manifestations
including recurrent Oral apthous ulcers, Genital ulcers, Uveitis , Skin lesions
Diagnosis is based on criteria proposed by the International Study Group for
Behcet’s Disease and includes the presence of recurrent oral ulcerations along
with at least 2 of the following:
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recurrent genital ulcerations
ocular lesions such as uveitis
skin lesions such as erythema nodosum
positive pathergy test
Other clinical manifestations include arthritis, vasculitis, gastrointestinal lesions
and central nervous system involvement, classically meningoencephalitis.
Behcet’s Disease
Onset is usually in the third decade although pediatric cases are not uncommon
Equal male to female affliction
Most prevalent in Turkey and the Middle East
Pathogenesis is multifactorial and not well understood
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Genetic predisposition, with high prevalence of the HLA-B51 allele in affected persons
Immune response to infectious triggers such as herpes simplex virus and Streptococcus species
Immune dysregulation
Inflammatory mediators have all been implicated
Prognosis and clinical course depends on the degree of systemic involvement with ocular lesions
causing most morbidity
Treatment is complex and also dependent on the systems involved but is typically a combination
of corticosteroids, both topical and systemic, immunosuppressant’s, cytotoxic agents, colchicine
and NSAID’s
Apthosis
Aphthosis or recurrent aphthous stomatitis
Painful, shallow ulcers covered by a grayish pseudomembrane and surrounded
by an erythematous halo that are typically present on the buccal mucosa,
tongue, soft palate and labial mucosa
Recurrent aphthous stomatitis is classified as either simple or complex
Apthosis
Simple aphthosis represents the common oral aphthous ulcer that is short lived
and heals within 7-10 days
Complex aphthosis represents recurrent, severe, oral and genital ulcerations
that are numerous, persistent and without manifestations of systemic disease
Complex aphthosis warrants further evaluation for underlying etiologies such as
hematologic abnormalities caused by nutritional deficiencies including iron,
vitamin B12 and folate deficiencies. Inflammatory bowel disease and celiac
disease must also be ruled out
Both typically present in children and adolescents and ulcers tend to decrease in
frequency and severity with age
Crohn’s Disease
A chronic inflammatory granulomatous bowel disease, remains a poorly recognized and often
misdiagnosed cause of vulvar disease in women
A recent review article looked at 55 cases of Crohn’s disease with vulvar involvement and found
that vulvar Crohn’s disease affects women aged 12-64 years most of whom are premenaupausal
Vulvar Crohn’s disease typically presents as swelling, pruritis and erythema and progressive
painful labial genital ulcers that can often develop into condyloma-like lesions and/or skin tags
Duration of symptoms ranged from 1-18 months
A biopsy is required for definitive diagnosis showing the typical non-caseating granulomatous
lesion
Treatment for the majority included metronidazole with or without prednisolone. Most of these
cases were published prior to the era of TNF and antibody suppressors treatments that are now
considered the mainstay therapy for patients with Crohn’s
PFAPA
The syndrome of periodic fevers, with apthous stomatitis, pharyngitis and
adenitis first described by Marshall in 1987 was subsequently termed PFAPA in
1989
PFAPA is diagnosed clinically through history, physical examination and over time
Typically presents before age 5, although in recent literature adolescent and
adult-onset PFAPA cases have been described
Characterized by periodic, abrupt onset high fevers, lasting an average of 5 days,
occurring at intervals of 3-8 weeks
These fevers must be associated with at least one of the 3 cardinal symptoms:
oral aphthosis, pharyngitis, or cervical adenitis
PFAPA
There is a notable absence of upper respiratory tract infections
The children are completely asymptomatic between episodes and have normal growth
and development
Cyclic neutropenia must be excluded by laboratory testing, which usually shows
leukocytosis and elevated inflammatory markers
There is a slight male predominance and no ethnic predilection
The exact pathogenesis is unknown
◦ infectious etiology vs immune dysregulation
A genetic basis for PFAPA has not been found and it has been described as a
nonhereditary autoinflammatory disease, characterized by episodic bouts of
inflammation without the presence of autoantibodies or autoreactive T cells
PFAPA
These children usually undergo an extensive investigation before the diagnosis is
made
No well established treatment for the syndrome, however, glucocorticoids,
cimetidine and colchicine have all been used with varying success
Recent literature has focused on tonsillectomy as a treatment for PFAPA
syndrome
Several studies, including a randomized clinical trial, have confirmed either
complete resolution or marked decrease in the frequency and severity of
episodes after tonsillectomy
Conclusion
With the exception of her somewhat older age, our patient fulfills the diagnostic
criteria for PFAPA
Given the constellation of her symptoms and specifically the presence of vulvar
ulcers, we considered other underlying etiologies before making the
presumptive diagnosis of PFAPA
The literature has reported several cases of genital ulcerations possibly as part
of the PFAPA clinical picture
References
• Huppert JS, Gerber MA, Deitch H, et al. Vulvar ulcers in young females: a manifestation of aphthosis. J Pediatri Adolesc Gynecol 2006;19:195-204
• Portnoy J, Ahronheim GA, Ghibu F, et al: Recovery of Epstein-Barr virus from genital ulcers. N Engl J Med 1984; 311:966
• Sisson BA, Glick L. Genital ulceration as a presenting manifestation of infectious mononucleosis. J Pediatr Adolesc Gynecol 1998;11:185
• Healy CM, Thornhill MH. An association between recurrent oro-genital ulceration and non-steroidal anti-inflammatory drugs. J Oral Pathol Med 1995;24:46
• McCarty MA, Garton RA, Jorizzo JL: Complex aphthosis and Behcet’s disease. Dermatol Clin 2003; 21:41
• Sakane T, Takeno M, Suzuki N, et al: Behcet’s disease. N Engl J Med 1999; 341:1284
• Andreani SM, Ratnasingham K, Dang HH et al. Crohn’s disease of the vulva. Internat J of Surg 2010;8:2-5
• Lee WI, Yang MH, Lee KF, et al. PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenitis. Clinical Rheumatol 1999;18:207-213
• Tasher D, Somekh E, Dalal I. PFAPA syndrome: new clinical aspects disclosed. Arch Dis Child 2006:981-984
• Renko M, Salo E, Putto-Lauria A, et al. A randomized controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. J
Pediatr 2007;151:289-292
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• Parikh SR, Reiter ER, Kenna MD, Robertson D. Utility of tonsillectomy in two patients with the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and
cervical adenitis. Arch Otolaryngol Head Neck Surg 2003;129(6):670-673
• Halvorsen JA, Brevig T, Aas T et al. Genital ulcers as initial manifestation of Epstein-Barr Virus infection: two new cases and a review of the literature. Acta Derma
Venereol 2006;86:439-42
• Gurler A, Boyvat A, Tursen U. Clinical manifestations of Behcet’s disease: an analysis of 2147 patients. Yonsei Med J 1997;38:423-35
• Ferguson MM,Wray D, Carmichael HA et al. Coeliac disease associated with recurrent apthae. Gut 1980;21;223-6
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