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Michael D. Tharp
The Clark W. Finnerud, M.D.
Professor and Chair
Department of Dermatology
Rush University Medical Center
Chicago, Illinois, USA
   Most common pigmentary disorder
   Patchy loss of pigment from the skin, hair
    and oral mucosa
   Reported frequency 0.1-2.0% in various
    populations
   Familial tendency with approximately 20%
    of probands having at least one affected
    first degree relative
   Autoimmune mediated?
Segmental              Clinical Features
Zosteriformis          macules distributed
                       along a dermatome

Non Segmental          Clinical Features
Localized or partial   few scattered macules
Acrofacialis           macules localized to
                       face, distal hands and
                       feet
Mucosal                macules on mucous
                       membranes
Generalized            more widespread
                       macules (face, hands,
                       feet, axillae, limbs)
   Thyroid disease
   Diabetes mellitus
   Adrenal insufficiency
   Lupus erythematosus
   Alopecia areata
   Myasthenia gravis
   Pernicious anemia
   Rheumatoid arthritis
   Sarcoidosis
   Chronic active hepatitis
   Vogt–Koyanagi–Harada syndrome
   Psoriasis
   Lichen planus
   C2 and C4 deficiency
   APS, autoimmune polyglandular syndromes
   Skin cancer/melanoma?
   A questionnaire was given to 2546 pts with
    vitiligo from the United Kingdom and U.S.

   Vitiligo pt groups:
     Vitiligo Society: UK
     National Vitiligo Society: USA
   A questionnaire was given to 2546 pts with
    vitiligo from the United Kingdom and U.S.
     Approx 70% female
     18% of first degree relatives had vitiligo
   19.4% of probands had autoimmune
    thyroid disease (88% hypothyroidism and
    12% hyperthyroidism)
   5.7% of first degree relatives with
    autoimmune thyroid disease
   1.9% had pernicious anemia
     13 fold increase over the general population
   0.38% with Addison’s disease
     76 fold increase over the general population
   8 fold increase in SLE
   2 fold increase in Crohn’s disease
   No increase in:
       alopecia areata
       diabetes mellitus
       multiple sclerosis
       myasthenia gravis
       psoriasis
       RA
       Scleroderma
       Sjogren’s synd.
CONCLUSIONS
 Vitiligo is associated with other autoimmune
  disorders
 Thyroid disease and pernicious anemia were
  frequent
 Addison’s dis, SLE and inflammatory bowel dis
  uncommon
 The above disorders also increased in
  probands’ first degree relatives: suggesting
  shared common susceptibility genes
   204 with vitiligo (0.61%) were obtained
    from 33,252 medical records:
       66% pts: localized vitiligo
       15% with generalized vitiligo
       13% with acromucosal vitiligo
       6% with segmental vitiligo

   Autoimmune disorders were found in 6
    (2.9%) of patients
   113 vitiligo pts were tested for diseases
    associated with polyglanduar autoimmune
    syndrome (APS)
   58% generalized vitiligo
   38% acrofacial vitiligo
   3% segmental vitiligo
Betterle, Acta Bio Med 74:9, 2003
   22 pts: APS-3C (thyroid and vitiligo)
   3 pts: APS-3B+C (thyroid, vitiligo and
    autoimmune gastritis)
   1 pt: APS-3C+A (thyroid, vitiligo, alopecia
    areata and anti-adrenal gland abs, + ANA
   5 pts: APS-4(vitiligo, myasthenia gravis,
    bullous pemphigoid, alopecia, autoimmune
    gastritis, +ANA)
Vitiligo      APS   APS APS APS
Type          3C    3B+C 4  3C+A

Generalized   11     3   3   1

Acrofacial    10     0   2   0

Segmental      1    0    0   0
(Anti-thyroid)   (Anti-gastic)
   22/113 pts with vitiligo had 3 or more autoimmune
    disorders (APS)
   Thyroid disease was common (39%)
   Addison’s disease rare (1/113) but higher frequency
    than the reported general population
   ANA positivity was seen in 3% of pts which is
    typical for the general population
   Recommend periodic screening of vitiligo pts for
    other autoimmune diseases
Clin Exp Dermatol 31,746,2006
   156 pts with vitiligo underwent an eye exam
   40% had some fundal abnormality
   Transillumination of the iris
     Whites 23%
     Blacks 5%
   Fundiscopic findings
     Focal pigment hypertrophy (18%)
     Hypopigmented spots (9%)
     Retinal scars (6%)
     Chorodial nevi (4%)
     Uveitis (1%): inflammation rarely seen
   Uveitis has been reported to be another ocular abnormality
    associated with vitiligo
   Vogt-Koyanagi_Harada syndrome (3 phases)
     Meningocephalic phase ( headache, meningismus, seizures and/or
        muscle weakness or paralysis) preceded by fever, nausea/vomiting :
        aspectic meningitis
       Acute ophthalmic phase (eye pain, photophobia, altered visual acuity):
        uveitis, iriditis, retinal detachment
       Otic involvement (dysacousia)
       Poliosis
       Vitiligo

   Alezzandrini syndrome
     Whitening of the hair, eyebrows and eyelashes
     Unilateral depigmentation of the skin on the forehead, nose, cheek,
        upper lip and chin along with decreased visual acuity and atropic iris

   Non-inflammatory depigmented lesions in the fundus seen in vitiligo
Thyroid disease
Diabetes mellitus
Adrenal insufficiency
Lupus erythematosus
Alopecia areata
Myasthenia gravis
Pernicious anemia
Rheumatoid arthritis
Sarcoidosis
Chronic active hepatitis
Vogt–Koyanagi–Harada
syndrome
Psoriasis
Lichen planus
C2 and C4 deficiency
APS, autoimmune
polyglandular syndromes.

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Vitiligo comorbities by Prof. Michael Tharp

  • 1. Michael D. Tharp The Clark W. Finnerud, M.D. Professor and Chair Department of Dermatology Rush University Medical Center Chicago, Illinois, USA
  • 2. Most common pigmentary disorder  Patchy loss of pigment from the skin, hair and oral mucosa  Reported frequency 0.1-2.0% in various populations  Familial tendency with approximately 20% of probands having at least one affected first degree relative  Autoimmune mediated?
  • 3. Segmental Clinical Features Zosteriformis macules distributed along a dermatome Non Segmental Clinical Features Localized or partial few scattered macules Acrofacialis macules localized to face, distal hands and feet Mucosal macules on mucous membranes Generalized more widespread macules (face, hands, feet, axillae, limbs)
  • 4. Thyroid disease  Diabetes mellitus  Adrenal insufficiency  Lupus erythematosus  Alopecia areata  Myasthenia gravis  Pernicious anemia  Rheumatoid arthritis  Sarcoidosis  Chronic active hepatitis  Vogt–Koyanagi–Harada syndrome  Psoriasis  Lichen planus  C2 and C4 deficiency  APS, autoimmune polyglandular syndromes  Skin cancer/melanoma?
  • 5. A questionnaire was given to 2546 pts with vitiligo from the United Kingdom and U.S.  Vitiligo pt groups:  Vitiligo Society: UK  National Vitiligo Society: USA
  • 6.
  • 7.
  • 8. A questionnaire was given to 2546 pts with vitiligo from the United Kingdom and U.S.  Approx 70% female  18% of first degree relatives had vitiligo  19.4% of probands had autoimmune thyroid disease (88% hypothyroidism and 12% hyperthyroidism)  5.7% of first degree relatives with autoimmune thyroid disease
  • 9. 1.9% had pernicious anemia  13 fold increase over the general population  0.38% with Addison’s disease  76 fold increase over the general population  8 fold increase in SLE  2 fold increase in Crohn’s disease  No increase in:  alopecia areata  diabetes mellitus  multiple sclerosis  myasthenia gravis  psoriasis  RA  Scleroderma  Sjogren’s synd.
  • 10. CONCLUSIONS  Vitiligo is associated with other autoimmune disorders  Thyroid disease and pernicious anemia were frequent  Addison’s dis, SLE and inflammatory bowel dis uncommon  The above disorders also increased in probands’ first degree relatives: suggesting shared common susceptibility genes
  • 11. 204 with vitiligo (0.61%) were obtained from 33,252 medical records:  66% pts: localized vitiligo  15% with generalized vitiligo  13% with acromucosal vitiligo  6% with segmental vitiligo  Autoimmune disorders were found in 6 (2.9%) of patients
  • 12.
  • 13. 113 vitiligo pts were tested for diseases associated with polyglanduar autoimmune syndrome (APS)  58% generalized vitiligo  38% acrofacial vitiligo  3% segmental vitiligo
  • 14. Betterle, Acta Bio Med 74:9, 2003
  • 15. 22 pts: APS-3C (thyroid and vitiligo)  3 pts: APS-3B+C (thyroid, vitiligo and autoimmune gastritis)  1 pt: APS-3C+A (thyroid, vitiligo, alopecia areata and anti-adrenal gland abs, + ANA  5 pts: APS-4(vitiligo, myasthenia gravis, bullous pemphigoid, alopecia, autoimmune gastritis, +ANA)
  • 16. Vitiligo APS APS APS APS Type 3C 3B+C 4 3C+A Generalized 11 3 3 1 Acrofacial 10 0 2 0 Segmental 1 0 0 0
  • 17. (Anti-thyroid) (Anti-gastic)
  • 18.
  • 19. 22/113 pts with vitiligo had 3 or more autoimmune disorders (APS)  Thyroid disease was common (39%)  Addison’s disease rare (1/113) but higher frequency than the reported general population  ANA positivity was seen in 3% of pts which is typical for the general population  Recommend periodic screening of vitiligo pts for other autoimmune diseases
  • 20. Clin Exp Dermatol 31,746,2006
  • 21. 156 pts with vitiligo underwent an eye exam  40% had some fundal abnormality  Transillumination of the iris  Whites 23%  Blacks 5%  Fundiscopic findings  Focal pigment hypertrophy (18%)  Hypopigmented spots (9%)  Retinal scars (6%)  Chorodial nevi (4%)  Uveitis (1%): inflammation rarely seen
  • 22. Uveitis has been reported to be another ocular abnormality associated with vitiligo  Vogt-Koyanagi_Harada syndrome (3 phases)  Meningocephalic phase ( headache, meningismus, seizures and/or muscle weakness or paralysis) preceded by fever, nausea/vomiting : aspectic meningitis  Acute ophthalmic phase (eye pain, photophobia, altered visual acuity): uveitis, iriditis, retinal detachment  Otic involvement (dysacousia)  Poliosis  Vitiligo  Alezzandrini syndrome  Whitening of the hair, eyebrows and eyelashes  Unilateral depigmentation of the skin on the forehead, nose, cheek, upper lip and chin along with decreased visual acuity and atropic iris  Non-inflammatory depigmented lesions in the fundus seen in vitiligo
  • 23. Thyroid disease Diabetes mellitus Adrenal insufficiency Lupus erythematosus Alopecia areata Myasthenia gravis Pernicious anemia Rheumatoid arthritis Sarcoidosis Chronic active hepatitis Vogt–Koyanagi–Harada syndrome Psoriasis Lichen planus C2 and C4 deficiency APS, autoimmune polyglandular syndromes.