Case Discussion

Paraneoplastic Pemphigus

Presented by Ri 吳曉婷 ,黃啟倫

陳 XX, 44 y/o married women

DM (-), HTN(-)

Denied other systemic disease

Denied any allergic history

Denied previous HSV infection

Basic Data

• The 44 y/o female patient visited our ER on 2002/04/01 due to refractory diffuse oral and pharyngeal ulcer for about 8 days.

• Besides, she had productive cough for about 1 month and conjunctivitis (LMD & herb medicine)

• Under the impression of Steven-Johnson syndrome related to HSV infection or drug, she was admitted to 15A ward for further care.

Brief History and Admission Course (I)

Brief History and Admission Course (II)

• Physical examination General appearance: ill-looking Consciousness: clear Conjunctiva: injected Sclera: anicteric Oral mucosa: diffuse erosion with yellowish crust

over the whole buccal and lingual mucosal surface

Brief History and Admission Course (III)

• 4/2 : admission and start IV steroid treatment; skin biopsy

was done

• 4/8 : Skin biopsy result (lower lip) : suprabasilar blister with

sloughed epidermis, pemphigus was likely

Fever was noted─ suspect UTI related

Empiric antibiotics were used

• 4/13 : DC steroid due to poor infection control

Brief History and Admission Course (IV)

• 4/14 : Skin biopsy (Back) : suprabasilar acantholysis with blister formation Direct immunofluoresence stain : linear C3 deposition at basement membrane zone IgG at intercellular space of epithelium check tumor marker: CA125(202.64)↑ Highly suspect paraneoplastic pemphigus• 4/15 : Abd. sonography : splenomegaly with hypoechoic lesion, susp. tumor infiltration (Lymphoma) No pelvic mass was noted

Brief History and Admission Course (V)

• 4/16 : Abd. CT :

1.Huge hypodense splenic tumor of 13x11x18 cm

2.Hypodense mass at the pelvis with ascites

3.1.2 cm hypodense lesion at liver

Imp: 1.Uterine tumor with spleen and liver metastasis

2.Non-Hodgkin’s lymphoma

Brief History and Admission Course (VI) Biopsy of the splenic tumor was unfeasible due to high hemorrhagic

risk→ diagnostic laparoscopic splenectomy was suggested Solumedrol 40mg q12h iv was used to control her pemphigus

activity

• 4/18 : consult infection specialist for poor control of infection intraperitoneal TB was suspected• 4/22 : fever subsided after four combined anti-TB therapy (Isoniazid, Rifampin, Pyrazinamide and Ethambutal). • 4/23 : scheduled for op but was postponed due to difficult intubation risk • 5/13 : operation

During Anesthesia

• Patient’s condition: WBC Hb PLT BP

9570 8.9 149K 65/110

• ETGA• Laryngoscopic intubation, with 7.0 mm tube fixed at 20cm,

checked by fibroscope• Agents : Rubinol, pentothol, Fentanyl, Atropin, S.C.C,

Atracurium, Enlon• Monitoring : CVP, pulse oxymetry, A-line, pressure cuff, ECG

pad• Cuff pressure < 20 cmH2O; Airway pressure < 15 cm H2O• Tidal volume < 10c.c./kg

• No vaseline gel was used over face

Extubtion

• Performed with fibroscope, no new visecles or bullae noted in the airway

• Could breath spontaneously• No airway obstruction• No hemoptysis• No skin lesion at the site of IV cannulation and BP

cuff placement• No lesion at pressure point• P’t was transferred to ICU

Post-operative Course

• Profound new vesicles were found when she was transferred back to the ward and the Solu-medrol was increased to 240mg per day. New vesicles stopped in 5 days and old ones healed almost completely.

Solu-medrol was tapered to 80mg per day after new vesicles stopped formation.

• Pathology of the splenic tumor revealed mixed small cleaved and large B-cell lymphoma

• BM aspiration : (+)• BM biopsy : (-)

Post-operative Course

• 5/22 : Epigastralgia WBC : 15990, Amylase : 1171, Lipase: 3695 Acute pancreatitis was likely Abd. CT showed acute pancreatitis with hemorrhage complication • 5/27 : Transfer to 13B ward for further care• 5/30 : Acute pancreatitis was controlled (Amylase :218; Lipase : 428; LDH: 1017) She was transferred to 12D ward for chemotherapy

Bullous Disease

• Pemphigus Vulgaris

• Pemphigus Foliaceus

• Paraneoplastic Pemphigus

• Bullous Pemphioid

• Cicatricial Pemphigoid

• Pemphigoid Gastationis

• Dermatitis Herpitifomis

• Linear IgA Bullous Dermatitis

• Epidermolysis Bullosa Acquisita

Pemphigus and Pemphigoid Disease

Level of acantholysis

Area involved Antigen

Pemphigus vulgaris

Suprabasilar layer

Skin & mucous

(stratified squamous epi.)

Desmoglein 3

Pemphigus foliaceus

Granular layer Skin(+)

Mucous(-)

Desmoglein 1

Paraneoplastic pemphigus

Suprabasilar layer

Numerous Desmoglein

Plakin, etc

Bullous pemphigoid

Subepidermal layer

Skin(+)

Mucous: little

BP230 Ag

BP180 Ag

Paraneoplastic Pemphigus

• Autoimmune disease that accompanies an overt or occult neoplasm and cause blisters

• The most commonly associated neoplasms: -- Non-Hodgkin’s lymphoma -- Chronic lymphocytic leukemia -- Castleman’s disease -- Thymoma -- Retroperitoneal scarcoma -- Waldenstrom’s macroglobulinemia

International Journal of Dermatology 2001,40:367-72

Lancet 1999, 354:667-72

Clinical Manifestations

• Mucosal: intractable stomatitis causing erosions and ulcerations in the oral mucosa

• Cutaneous: trunk and proximal extremities flaccid or tense blisters with or without erosions

• Respiratory: obstructive ventilatory defect inflammation, vesiculation of tracheobronchial epi.

Airway Involvement

Histology P. vulgaris PNP

Tongue Stratified squa. epi. Yes Yes

Floor of the month Stratified squa. epi Yes Yes

Soft palate Stratified squa.epi. Yes Yes

Oropharynx Stratified squa. epi. Yes Yes

Nasopharynx Pseudostratified ciliated columnar epi*

Yes Yes

Larynx Pseudostratified ciliated columnar epi*

Yes Yes

Trachea & bronchus Pseudostratified ciliated columnar ep

No Yes

Immunologic Studies

• Immunoprecipitation studies: gold standard for the diagnosis of paraneoplastic pemphigus

• Respiratory and urinary bladder epi: desmoplakin(+), desmoglein(-) for distinguishing paraneoplastic pemphigus from other forms of pemphigus

Pathogenesis

• Combination of humoral and cell-mediated autoimmunity

• Neoplasm of immune origin may cause dysregulation of immune system

• Antigenic components that cross-react with epidermal cell surface proteins

Diagnosis

Respiratory Failure in Paraneoplastic Pemphigus

• Bronchiolitis obliterans • Infection, toxic effects induced by chemotherapy,

neoplasia and autoantibody-mediated pulmonary injury

• Acantholysis with deposits of IgG in the bronchial epithelium.

• Antiplakin antibodiesNEJM 1999; 340(18): 1406-10, 1999

Case 1

• 46 y/o female• Abdominal hysterctomy and bilateral salphingo-

oophorectomy• Pemphigus vulgaris for 8 years• Prednisone 10mg + azathioprine 100mg• PE: painful bullous formations in the mouth and

oropharynx

Regional anaesthesia in pemphigus vulgaris. Anaesthesia, 1992; 47:74

Process and Results

• Spinal anesthesia• Hydrocortisone 100mg iv. preoperative and

during surgery• 25-gauge spinal needle inserted at the L2-3• No lesions at the site of spinal needle puncture,

blood pressure cuff, intravenous cannulation, or oxygen mask application (the face has been pretreated with vaseline gel)

Case 2

• 45 y/o man• Exploratory laparotomy for suspected PPU• Pemphigus vulgaris with bullae over face, trunk,

extremities, oral cavity and pharynx• Prednisolone 60mg/day + NSAID

Anaesthetic management of a patient with pemphigus vulgaris for emergency laparotomy. Anaesthesia 2000; 55:155-162

Process and Results

• General anesthesia• Monitors: CVP, A-line, pulse oximetry, end-tital gas

monitoring• Facial lesions were covered with 1% hydrocortisone cream

and soft cotton sponges before placing the facemask• Pre-OP laryngoscope: bleeding from mucosal lesion of

oropharynx throat pack soaked with saline adrenaline• Induction: thiopental + succinylcholine• Maintenance: NO 66% + halothane 0.5% in oxygen• Extubation under deep halothane anesthesia• Hydrocortisone pre-operative and post-operative

Case 3

• 49 y/o female, Stage IV vulvar carcinoma• Radical vulvectomy and bil. femoral and pelvic node

disection• Bullous pemphigoid diagnosed 2 months before• Admitted for iv steroid administration and hydration

before surgery due to poor control• Prednisone 80mg + azathioprine 50mg bid• PE: ulcerated lesion on the lower gums, no intraoral

lesionsAnesthetic management of a patient with bullous pemphigoid.

Anesth Analg 1989; 69:537-40

Process and Results

• Spinal anesthesia

• Premedicated with morphine, scopolamine and hydrocortisone

• Adhesive tape, the IV catheter, precordial stethoscope, ECG pads and blood pressure cuff as usual

• New bullous and erythematous lesions of the face and inframammary area

• No lesions at the site of spinal needle puncture, blood pressure cuff placement, or IV cannulation

• No lesions at pressure points

Discussion

• New bullae formation

• Infection and dehydration

• Side effects of medication

• Choice of anesthesia

• Endotracheal intubation

New Bullae Formation

• Prevention of :

-- friction and trauma

-- local anesthesia infiltration

-- spirit swab

-- adhesive tape

-- ECG electrodes and blood pressure cuff

Infection and Dehydration

• Fluid replacement for dehydration

• Correct electrolyte abnormalies

• The choice of injection site should be away from skin lesion

Side Effects of Medication

• Steroid

-- sodium and fluid retention, hypokalemic alkalosis,

peptic ulcer, hyperglycemia, impaired wound healing

• Azathioprine

-- reversible leukopenia and thrombocytopenia, secondary to bone-marrow supression, and hepatotoxicity with biliary stasis

Choice of Anesthesia

• Controversial• Ketamine• 131 patients, ETGA

-- no intraoperative or postoperative airway

obstruction

-- 6 instances of facial and intraoral bullae

formation

Endotracheal Intubation

• ET tube should be liberally lubricated

• Face and lips should be pretreated with 1%hydrocortisone cream and vaseline gel

• Maintaining minimal cuff inflation pressure

• Macintosh rather than a Miller laryngoscope blade

• Smaller tube

• ET tube should be secured with a soft cloth bandage

• Postoperative laryngoscope?

In Our Patient

• Potential of more generalized involvement

• Avoid of adhesive tape

• Avoid of ECG electrodes and blood pressure cuff if possible

• Pretreatment of face and lip

• Smaller ET tube

Thanks For Your Attention