Grandround:  1/14/2015

Unit  7c

Prof  T.M.Munyao.

Department  of  Clinical  Medicine  and  Therapeutics.

Pemphigus  Vulgaris

Outline

• Summary:  Case  presentation    • Background:  Definition,  Blistering  diseases.    • Presentation.  • Complications.  • Diagnosis.  • Differential  diagnoses  • Management.  • Conclusion.

Summary:  Case  presentation.

• 44  year  old  patient  ,  diagnosed    in  2009.    

• Good  control  on  follow  up  for  3  years  (2012).  

• Absconded,  presented  with  a  flare  in  term  pregnancy  after  2  years  

July  2014.  

• Uneventful  pregnancy,  controlled  on  prednisone  10  mg  od.  

• Treatment  stopped  28/12/14.  Admitted  in  flare  on  5  Jan  2015.

Background.

Definition:

Pemphigus  vulgaris.    

Common  potentially  life  threatening  immunobullous  disorder    characterised  by  flaccid  vesicles  and  bullae  and  erosions  due  to  suprabasal  epidermal  clefts.

Blistering  (Vesiculobullous)  diseases.

• Clinical  Syndrome.  

• Disorders  of  cohesion  failure  of  structural  proteins.  

• Hereditary  due  to  genetic  mutations.  

• Acquired:  Autoimmunity,  drug  induced  or  paraneoplastic.  

Pemphigus  vulgaris.

Pathophysiology.  

• Circulating  IgG  autoantibodies.  

• Bind  to  desmoglein  3  in  suprabasal  keratinocytes  desmosomes.  

• Non  inflammatory  stereotactic  clefts.  • Acantholysis

Presentation.

• Adults,  no  gender  predisposition,  1-­‐2/1m  population.  

• Primary  lesions:  spontaneous  Skin:  Flaccid  bullae  and  vesicles  Mucous  membranes-­‐  erosions  Positive  Nikolsky  and  Asboe  Hansen  sign  positive.  

• Secondary  lesions  Skin:  erosions,  crusting,  scaling  collarettes,  dyspigmentation.

Pemphigus..

• Lesions  are  frequently  secondarily  infected.  

• Oral  lesions  may  preceed  skin  lesion  by  months  or  years.  

• Causes  impairment  of  feeding  due  to  pain.  

• Erosional  lesional  surface  area  of  >30%  body  surface  area  deemed  ‘cutaneous  failure  syndrome’  

Further  clinical  history:

• Explore  exposure  to  drugs:  captopril,  frusemide  etc  

• Consider  malignancy  as  per  risk  and  indicators.

Complications.

• Sepsis.  • Cutaneous  failure.  • Exfoliative  erythroderma.

Diagnosis.

• Clinical  features  • Histology            Deep  seated  Suprabasal  clefts  with  acantholytic  keratinocytes.  

• Immunofluorescence        Direct-­‐Non  lesional  tissue  reticulate  pattern        Indirect:  IgG4.  • Immunoprecipitation,  immunoblotting  

Differential  diagnoses.

• Pemphigus  foliaceous  • Pemphigoid  group.  • SSSSyndrome  • Fixed  drug  eruption.

Management.

• Holistic  diagnosis  and  management.  • Cutaneous  failure  management  • Skin  lesional  care  • Systemic  therapy:  Prednisone  1mg/kg  bwt,  <21  days,  scale  down  gradually  initially  by  1/3rd  and  less  subsequently.  Maintainace  dose  15-­‐30  mg/day.  Follow  pt.  

• Combination:  Steroid  sparing:  Azathioprine,  Cyclophosphamide,  Methotrexate  

• Rituximab.  • IVIG,  Plasmaphresis.

Prognosis.

• Undiagnosed/unmanaged  cutaneous  failure>70%  

• Counselling,  Control  and  follow  up.  • Least  immunomodulation  dose  for  remission.

Conclusion.

• Pemphigus  is  a  common  and  serious  immunobullous  disease.  

• Adverse  outcomes  are  preventable  by  prompt  holisic  diagnosis  and  management.

• Thank  you.