Transcript case report

case report
Names of your group members ?
History of illness
 Shuang Jukun, male, 36 years old. Admission date: Mar 2nd,2012.
 Chief complaint: oral mucosal erosion for 3 months, vesicles and
erosion on face, trunk and extremities for 1 month.
 History of present disease: 3 months ago, the patient complained of
oral erosion with no obvious precipitating cause. 1 month ago,
vesicles and bullae started appearing on his knees, generalizing
eventually to the extremities, face and trunk. Vesicles broke down
easily to form erosion. He was diagnosed to be suffering from
pemphigus vulgaris at the local hospital and was treated with methyl
prednisolone 120~240 mg/d for 20 days with little improvement. He
was subsequently seen at our department for diagnosis and
treatment.
 History of past illness: negative. No medicine taken.
 History of familial illness: negative.
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Physical examination
 T: 37.1℃(Celsius degree)
Pulse: 90 bpm
Respire: 20
breath per minute
BP:130/80 millimetre of mercury
 Systemic examination: normal. Genitalia is normal.
 Specific examination: thick greyish white crust on his scalp.
Conjunctival hyperemia. Erosion on periocular skin and oral mucosa.
Extensive moist reddish erosion on his face, neck, trunk and
extremities, with bleeding. Nikolsky‘s sign (+). Neck, axilla, and groin
creases are covered by yellowish discharge.
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Pathology?
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Defining characteristics
 Male youth with chronic course of
disease
 Oral mucosa erosion. Extensive
vesicle and bullae easily to break.
Nikolsky's sign (+).
 Pathology showed bullae above
basement membrane. DIF found IgG
and C3 deposition in spinous cell.
Serum Dsg1 Ab and Dsg3 Ab
elevated.
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Diagnosis: pemphigus vulgaris
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Clinical features — Pemphigus vulgaris is characterized by
flaccid bullae that typically begin in the oropharynx and then may
spread to involve the skin, with a predilection for the scalp, face,
chest, axillae, and groin. The bullae rupture easily, so that the
patient often presents with only erosions and no intact bullae .
Virtually all patients have oropharyngeal disease at some point in
the course of disease. Other mucous membranes may also be
involved . A Nikolsky sign may be present
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Lesions typically are painful, particularly after the blisters
rupture. Open denuded areas can become secondarily infected.
Severe oral involvement may impair oral intake. Lesions do not
resolve without therapy and often heal with postinflammatory
hyperpigmentation. The pigmentary changes generally resolve
within one to two years and do not leave scarring.
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Diagnosis — The diagnosis of pemphigus requires biopsy of skin
lesions. A deep shave or 4-mm punch biopsy should be
performed for routine light microscopy from an early, small
vesicle or from the edge of a new erosion; histologically there is
evidence of intraepithelial acantholysis without disruption of the
basement membrane
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Enzyme-linked immunosorbent assay (ELISA) — Enzyme-linked
immunosorbent assay (ELISA) is also useful for the diagnosis of
pemphigus, and can assist with the identification of the
pemphigus subtypes. Patients with pemphigus foliaceus will
exhibit serum positivity for antibodies against Dsg 1, but not Dsg
3. Individuals with pemphigus vulgaris with both mucosal and
cutaneous features are typically positive for both Dsg 1 and Dsg 3
antibodies. Patients with mucosal-predominant pemphigus
vulgaris often have an assay that is positive for only Dsg 3.
Measurements of circulating autoantibodies against Dsg in serum
specimens correlate loosely with clinical activity and can be
useful for gauging disease activity in some patients
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PEMPHIGUS FOLIACEUS
Pemphigus foliaceus occurs less commonly than pemphigus
vulgaris in the United States and Europe, but is more prevalent in
Africa . It is characterized by erythema, scaling, and crusting that
first appears on the face and scalp , and later involves the chest
and back . An endemic form, occurring in certain areas of Brazil,
is called fogo selvagem; other endemic forms have been
described as well . Histologically the lesions are more superficial
so that erosions, rather than blisters, are typically observed.
Unlike pemphigus vulgaris, mucous membrane involvement does
not occur. The drugs most often implicated are penicillamine and
other thiol (SH) compounds, including captopril, or drugs such as
piroxicam that are metabolized to thiols
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PARANEOPLASTIC PEMPHIGUS
Paraneoplastic pemphigus occurs in patients with a known or
occult neoplasm. It is typically associated with lymphoreticular
malignancies, including non-Hodgkin lymphoma, chronic
lymphocytic leukemia, Castleman's disease, thymoma, and
Waldenstrom's macroglobulinemia.
Patients with paraneoplastic pemphigus often have severe
mucocutaneous disease with ocular and oral blisters and skin
lesions that resemble erythema multiforme, bullous pemphigoid,
or lichen planus . This can be the initial presentation of
malignancy or may occur in individuals with a known neoplastic
process. A clue to the presence of paraneoplastic pemphigus in the
former case is the presence of apparently severe oral pemphigus
with atypical cutaneous findings.
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Differential Diagnosis
The differential diagnosis of pemphigus vulgaris includes:
If mouth erosions predominate, consider herpes simplex virus,
aphthae, lichen planus, or erythema multiforme
If widespread erosions predominate, consider pyoderma,
impetigo, or other bullous diseases (eg, bullous pemphigoid,
bullous drug eruptions)
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Differential diagnosis
Erythema multiforme and Stevens-Johnson syndrome / toxic
epidermal necrolysis — Erythema multiforme and Stevens-Johnson
syndrome are hypersensitivity reactions that often present with both
skin lesions and mucosal involvement. Erythema multiforme is
frequently related to herpes simplex infections, but also may be
caused by other infections (eg, Mycoplasma pneumoniae) or
medications, or may be idiopathic. Stevens-Johnson syndrome is
most commonly induced by drugs. Target skin lesions are a
characteristic feature of erythema multiforme; erythematous,
purpuric macules and sloughing skin may occur in Stevens-Johnson
syndrome.
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Different Diagnosis
Bullous Pemphigoid (BP)
 BP most frequently affects elderly people.
 BP is mediated by autoantibodies that bind to the bullous
pemphigoid antigens 230 and 180.
 BP often starts with pruritus and exhibits urticarial and
erythematous lesions. Later, large, tense blisters develop both
on erythematous and normal skin, most bullae rupture within a
week, leaving an eroded base that, unlike the situation with
pemphigus, does not spread and heals rapidly. Nikolsky`s sign
is negative.
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?bullous pemphigoid
 Bullous pemphigoid — A common presentation for bullous pemphigoid is a widespread
blistering eruption in a middle-aged or elderly patient who is taking multiple
medications. Proper diagnosis is especially important to determine if the bullae are due
to bullous pemphigoid or are drug-induced, so that the etiologic agent may be identified
and removed.
 The eruption is usually generalized, sites of predilection being the trunk and limbs,
mucosa can also be involved.
 The histopathology shows subepidermal blisters, often filled with eosinophils. Direct
immunofluorescence shows a linear band of IgG and C3 along the basement
membrane zone.
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Dermatitis Herpetiformis
 Dermatitis herpetiformis usually begins in the
second to fifth decades.
 Dermatitis herpetiformis presents initially with a few
mild itchy papules or vesicles, but in time the
disease evolves into its classic presentation of
intensely burning urticarial papules, vesicles, and
rarely bullae, either isolated or in groups such as in
herpes simplex or zoster.
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?dermatitis herpetiformis
 Blisters are usually distributed symmetrically on the areas of elbows, knees, scalp,
neck, shoulder, and buttock. Mucosal involvement occurs rarely.
 Microabscesses composed mainly of neutrophils and a few eosinophils are found in the
subepidermal vesicles and dermal papillae. Direct immunofluorescence shows granular
IgA, usually accompanied by C3 deposits in the dermal papillae and superficial dermis.
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Linear IgA Bullous Dermatosis
 LABD is divided into childhood LABD, whose
symptoms appear in children under age 10,and adult
LABD, which occurs in adults aged 40 or older.
 Erythema multiforme-like lesions and tense blisters
occur over the entire body accompanied by intense
itching which are similar to the manifestations of
dermatitis herpetiformis.
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Linear Ig A Bullous Dermatosis
 Lesions may also occur in the mucous membranes. The lesions tend to aggregate on
the genitalia and inner regions of the thighs in children. In some cases, it may heal
spontaneously.
 Subepidermal blistering is evident. By direct immunoflorescence, linear IgA and C3 can
be found along the epidermal basement membrane in samples taken from normalappearing skin around the lesions.
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Laboratory test results
 Complete blood count
Leukocyte count : 13
15×109/L, Neutrophil counts : 76
80%
 Biochemistry:
Albumin: 24
29g/L, ALT: 102
60U/L, AST: 111
38U/L
 Desmoglein antibody test:
Dsg1 Ab: 236.9U/ml, Dsg3 Ab: 197.4U/ml
 Microbiological tests :
4/3 swab culture (erosions along creases): Proteus vulgaris,
7/3 fungal microscopy and swab culture of erosions and oral mucosa :
negative
9/3 blood bacterial cultures: negative
15/3 swab cultures (erosions along creases): Methicillin-resistant
Staphylococcus aureus(MRSA)
15/3 sputum microscopic examination: aspergillus x 2
20/3 sputum culture: aspergillus
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Treatment
Proper therapeutic[,θerə'pju:tik] choices are
determined by the patient’s age ,the degree
of involvement, the subtype of
pemphigus,and the progression of the
condition .
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 Treatment — Patients should be referred to a
dermatologist for initial consultation and management of
the disease. Long-term follow-up is the rule; some
patients require years to life-long suppressive therapy. A
minority of patients (approximately 10 percent) achieve
complete remission after initial treatment and do not need
continued drug therapy; the majority require maintenance
therapy to stay in remission
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1.systemic glucocorticoids[,glu:kəu'kɔ:ti,kɔid]
 low-dosage (45–60 mg/d) with high-dosage (120–180 mg/d)
prednisone did not demonstrate a difference in any
outcome, including the time to disease control and relapse
rate. All patients achieved remission; however, most expert
opinions suggest the initial use of 1 mg/kg/d corticosteroids.
 Steroids ['stiərɔidz] have been used as the baseline treatment
and cornerstone of pemphigus management since the 1950s.
 Average amount： 60–120 mg/d prednisone.
 Indicators of treatment response：new blister formation,
healing of existing erosions, the resolution of the positive
Nikolsky’s sign and serum antibody levels
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 If poor treatment response after 1 week, the dose should
be increased by a third or a fourth of the initial dose. Be
aware of the need to also treat secondary bacterial infection.
 After lesions are controlled ,we should continue steroid
treatment for another 2 -3 weeks before tapering the dose
 Maintenance dose: 10–15mg/d, or 20–30 mg/d, oral
formulations, every other day dosing (e.o.d)
 For severe cases: Pulsed therapy 250–1000 mg/d
methylprednisolone for 3-5 days. Repeat pulsed therapy can
be considered after an interval of 15-30days.
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2.Immunosuppressive Therapies
 Cyclophosphamide [,saikləu'fɔsfəmaid]
 Cyclophosphamide is an alkylating agent that selectively
inhibits lymphopoietic cells while sparing hematopoietic
[,hemətəupɔi'i:tik] cells. It has been shown to be useful in a
wide variety of autoimmune conditions by inhibiting cyclical
production of antibody-producing B lymphocytes.
 There is a significant steroid sparing effect when combined
with steroids as compared with prednisone alone .
 Dosage 1.5–2.5 mg/kg/d.
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Azathioprine[,æzə'θaiəpri:n]
Azathioprine is a purine synthesis inhibitor
originally developed for use in organ
transplantation.
Dosage 1.5–2.5 mg/kg.d.
Mycophenolate ? More details
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 Comparison of the steroid-sparing capacities of azathioprine,
mycophenolate, and cyclophosphamide has shown no significant
benefit or detriment of one particular treatment over another with the
evidence available at hand.
 Drug safety is another aspect to take into consideration when
choosing an appropriate therapeutic modality. Cyclophosphamide
carries significant health risks, including fertility issues and long-term
cancer risks .
 Azathioprine has risks of hepatotoxicity and myelosuppression, which
are also side effects shared with mycophenolate mofetil and
cyclophosphamide .
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 In terms of cost, mycophenolate is more expensive than azathioprine
and cyclophosphamide.
 This can be a disincentive to patients as well as health care providers
 Expert opinion often recommends that cyclophosphamide be avoided
for safety reasons.
 At this stage, selection of immunosuppressive agents is on an
individualized basis, taking into consideration patient age, fertility, and
comorbidities.
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Antiinflammatory Therapies
 Dapsone
 Sulfasalazine and pentoxifylline
 Intravenous immunoglobulin (IVIG) has been used as a component of
combined therapy for severe pemphigus since 1989.
 There was also a benefit in terms of reduced pemphigus activity
score 19??? and reduced antibody titres demonstrated with IVIG
therapy.
 Plasmapheresis
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Topical Therapies
 Topical epidermal growth factor
 Topical pimecrolimus
 Traditional Chinese Medicine
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SUMMARY
 The optimal therapeutic [,θerə'pju:tik] strategy for
pemphigus vulgaris and pemphigus foliaceus is not known.
With multiple treatment modalities and regimens available,
treatment choice is complex.
 Systemic glucocorticoids are central to the effective
management of pemphigus, although evidence is not clear as
to the optimal dose or regimen.
 Evidence supports a steroid sparing role for adjuvant
immunosuppressants or modulatory agents; although, there
were no associated direct benefits in terms of remission or
disease control.
 Topical preparations seem to decrease the time required for
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of erosions.
Any management strategy for individual patients
should include consideration of potential benefits
and adverse events unique to the individual patient.
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 Methyl
prednisolone:
2/3 500mg × 3 days
 Cyclophosphamide:
•Antibacterial:
•Antifungal:
2/3 1g for once
↓
5/3 250mg × 3 days
↓
7/3 120mg × 5 days
12/3 80mg × 4 days
•7/3 Penicillin G
4 million U bid × 2 days
↓
 9/3 Intravenous
•9/3 Cefoperazone and
immunoglobulin IVIG: Sulbactam 1.5 bid × 5
days
20g × 3 days
•14/3 Imipenem and
Cilastatin 1g bid × 4
days
 Prednisone PO:
↓
19/3 30mg bid × 5
days
•18/3 Levofloxacin 0.3 ×
3 days
•12/3 Fluconazole
0.1 bid × 6 days
•18/3 Voriconazole
0.2 bid
↓
24/3 25mg bid
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Progress and Prognosis
 After treatment of this case at our department, more than 80% of the
surface area affected by vesicle formation and erosions underwent
epithelialization with a resolution of fever. There were no new vesicle
formation and there was disappearance of the positive Nikolsky‘s
sign.
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Thank you for your attention !