vitiligo in association with erythema dyschromicum perstans
DESCRIPTION
Twenty seven years old female patient two years ago after delivery has noticed appearance of irregular hypo- and achromic macules on her trunk, extremities and face. Two months ago she has seen on her trunk and extremities oval gray-blue hyperpigmented macules which are accompanied from a slight pruritus.She has common complains of weight reduction of 5-6 kg, palpitation, sleep disturbance, fatigue and some joint pain. Clinically our patient is IV phototype. She has two different type of exanthema. First type - vitiligo is presented from symmetrical distributed over the trunk, extremities and face hypopigmented and achromic macules from 0,5 cm to 20 cm in diameter. The second type exanthema has symmetrical distribution and involves abdomen, back and proximal part of extremities. The lesions are gray-blue macules with oval shape and size from 0,5 cm to 2 cm in diameter. There is no change in mucous membrane.Deviations of the investigations include slight elevated ECR, reduced HGB, HCT, MCV, MCH, MCHC, monocytosis, reticulocytosis, low serum Fe, increase TIBC, decrease LDH, positive serological test for H. pylori, increased Tg-Ab and TSH-RAb, very low TSH, elevated FT4, nasal smear – S. aureus, vaginal smear – S. agalactiae. Ultrasound of thyroid gland shows normal topic, size, structure and enhanced blood flow.Conducted by the clinical laboratory research fund and consultative examinations are specified comorbidities Grave’s disease, iron deficiency anemia, bacterial colpitis, and chronic gastritis.Histopathological examination of the edge or the hyperchrome lesion show minor hydropic degeneration of basal layer, sparce, superficial, perivascular lymphocyte infiltrat, and macrophages containing melanin (incontinentia pigmenti).Differentially were discussed lichen planus, postinflammatory hyperpigmentation, contact dermatitis, fixed drug reaction.Based on the anamnesis, clinical picture, laboratory results and conducted histological examination answer the question what is this second type exanthema is Erythema dyschromicum perstans.Conducted treatment for accompanying diseases is with Ciprofloxacin, Ferrous sulfate, Vitamins, Thiamazol, eradication therapy for H. pylori and local application of Mupirocin nasal ointment. We have made 7 procedures UVB 311 nm narrow band with slight improvement.There are only few previously described cases of Erythema dyschromicum perstans & vitiligo in the same patient. These cases include patients with darker skin. In both diseases there is HLA-DR4 association in the pathogenesis. There are some common features between two diseases which include predominance of cytotoxic T-cell and almost the same ratio of CD4/CD8, Ia antigen positivity in the dendritic cells in epidermis and dermis and increased number of epidermal Langerhans cells. - Disclaimer- This PPT is loaded as student material "as is", from the VRF Vitiligo Master Class Barcelona November 2011; VRF does not endorse or otherwise approve it.TRANSCRIPT
VitiligoVitiligoin association within association with
Erythema dyschromicum perstansErythema dyschromicum perstans
Violina Todeva Violina Todeva 11
E. Hristakieva, D. Karshakova, D. Gancheva 1
S. Yordanova 2
1 University Clinic Stara Zagora, Bulgaria Department of Dermatology and Venereology2 Medical Institute - Ministry of Interior, Bulgaria Department of Endocrine Diseases
AnamnesisAnamnesis
Duration: 2 years Trigger: childbird
Presentation: irregular hypo- and achromic macules
Localisation: trunk, extremities, face
Subjective complaints: (-) Therapy: supplements
P.M.R., ♀♀ 227 years7 years
Clinical FindingsClinical Findings
Mucous membranes and skin appendages - unchanged
IV phototypeIV phototype
Symmetrical distribution Trunk, extremities, face Diameter – 0,5 – 20 cm Irregular shape Sharply circumscribed Hypopigmented macules Achromic macules
Clinical FindingsClinical Findings
Mucous membranes and skin appendages - unchanged
Symmetrical distribution Trunk, extremities
Diameter – 0,5 – 2 cm Oval shape, gray-blue macules
InvestigationsInvestigations
Hematological tests ESR - 20/40 mm; HGB - 110g/l; HCT - 0,34 L/L; MCV - 80 fL; MCH -
25,2 pg; MCHC - 315 g/L; Mo - 11%; Ret - 9‰; Biochemical tests
Serum Fe - 6,1 µmol/L; TIBC - 65,5 µmol/L, LDH - 105 U/L Serological tests
H. pylori - 8,0 U/ml Immunological tests
Tg-Ab - 219 IU/ml, TSH-RAb - 7 IU/mL Hormonal tests
TSH - 0,038 mIU/L, FT4 - 26,07 ng/L Microbiological tests
Nasal smear - S. aureus; vaginal smear - S. agalacticae Parasitological tests
Negative Urine
Referent
Laboratory testsLaboratory tests
InvestigationsInvestigations
Ultrasound of thyroid gland normal topic, size and structure enhanced blood flow
Instrumental tests:
Endocrinologist
Haematologist
Gastroenterologist
Rheumatologist
Consultations:
Comorbidities
Grave’s disease
Iron deficiency anemia
Bacterial colpitis
Chronic gastritis
HystopathologyHystopathology
Epidermal changes increased epidermal
pigment hydropic degeneration of
basal layer
Dermal changes incontinentia pigmenti
(Macrophages containing melanin)
sparce, superficial, perivascular lymphocyte infiltrat
H&E x 20 H&E x 40
Erythema dyschromicum perstansErythema dyschromicum perstans
Contact dermatitis Fixed drug reaction Addison disease Hemochromatosis Secondary syphilis Urticaria pigmentosa Macular amyloidosis Late pinta Leprosy
Lichen planus – pigmentosus et actinicus Postinflammatory hyperpigmentation
TherapyTherapy
Emollients Mupirocin nasal ointment
Systemic
Local
Ciprofloxacin 2x500 mg Ferrous sulfate 1x325 mg Vitamins (Vit.B6, Vit.B9, Vit.C) Thiamazol 2x10 mg H. pylori eradication
UVB 311 nm narrow bandPhysical
VitiligoVitiligo
Incidence 0,1-3%
Peak 2nd and 3rd decade
Children 25% of all patients
Gender ♂ : ♀ up to 1:1,3
Ethnic, racial incidence equal
Socioeconomic factors irrelevant
Family history 20% - 30%
Monozycotic twins 23% concordance
Epidemiology
Dermatology for skin of color, A. Kelly, S. Taylor, 2009, p. 317-318, p.99
Etiology & Pathogenesis of Vitiligo
Autoimmune hypothesis, humoral and cell-mediated immune aberrations Common linkages with other autoimmune diseases Increased frequency of organ specific Ab Melanocyte Ab, tyrosinase and tyrosinase-related proteins 1 and 2 Ab, MCHR1 Ab Activation of cytotoxic T-lymphocyte, decrease in helper T-lymphocyte Elevated levels of IL-2 in blood and skin, lesional skin expression TNF-α, IL-6, IF-γ
Genetic predisposition Multifactor, polygenetic disorder HLA-DR4, -Dw7, -DR7, -DR1, -B13, -Cw6, -DR53, -A19 Chromosomes – 1, 2, 7, 8, 11, 17, 19, 22
Viral infection CMV HSV
Neural theory Segmental vitiligo Peripheral nerve ending released compounds that may inhibit melanogenesis – neuropeptide Y Lesional autonomic dysfunction – increased sweating
Oxidative stress Blood – low catalase and glutathione, elevated superoxide dismutase, xanthine oxidase Skin – defective recycling of tetrahydrobiopterin, increased hydrogen peroxide, decreased
catalase Self-destruction/ Autocytotoxic
Formation of phenolic compounds during synthesis of melanin Environmental compounds – catechols, phenols, sulfhydryls
Dermatology for skin of color, A. Kelly, S. Taylor, 2009, p. 318-319
Clinical manifestation of Vitiligo
Localized Focal: one or more patches in the same area; Segmental: limited to a dermatome or Blashko
lines; Mucosal: only mucous membranes.
Generalized Vulgaris – disseminated lesions without region
predilection; Acrofacialis – distal extremities and facial
(periorificial) Lip-tip variety
Universalis Complete or almost complete depigmentation
Clinical variants Trichrome, Quadrichrome, Pentachrome Confeti type
Thieme Clinical Companions, Dermatology, W. Sterry et all, p.375Fitzpatrick,s Dermatology in general medicine Klauss Wolf, 2008, 617-618
Vitiligo & associated disordersVitiligo & associated disorders
Rook’s Textbook of Dermatology, 2010, p.58.46Fitzpatrick’s Dermatology in general medicine Klauss Wolf, 2008, 619
AUTOIMMUNEDISEASES
Vogt-Koyanagi-Haradasyndrome
Ocular disorders
Alezzandrinisyndrome
Morphoealichen sclerosus
Aseptic meningitis
Premature grayingPoliosis (Leucotrichia)
Malignant melanomaHalo naevus
VITILIGO
Thyroid – Graves disease, Hashimoto thyroiditis Addison disease Diabetes mellitus Hypoparathyroidism Pernicious anemia Alopecia areata Myasthenia gravis Autoimmune polyendocrine syndromes
Classification of the APSClassification of the APS
APS-1 Chronic candidiasis, Chronic hypoparathyroidism, Addison’s
disease (at least two present) APS-2
Addison’s disease (always present) + autoimmune thyroid diseases and/or type 1 diabetes mellitus
APS-3 Autoimmune thyroid diseases associated with other
autoimmune diseases (excluding Addison’s disease and/or hypoparathyroidism)
APS-4 Combinations not included in the previous groups
Betterle C.; Zanchetta R., Update on autoimmune polyendocrine syndromes (APS). Acta Biomed Ateneo Parmense 2003;74:9-33
Autoimmune polyendocrine syndromesAutoimmune polyendocrine syndromes
Autoimmune polyendocrine syndromes type IIIAutoimmune polyendocrine syndromes type III
Betterle C.; Zanchetta R., Update on autoimmune polyendocrine syndromes (APS). Acta Biomed Ateneo Parmense 2003;74:9-33
AUTOIMMUNE POLYENDOCRINE SYNDROMES TYPE 3AUTOIMMUNE POLYENDOCRINE SYNDROMES TYPE 3
AUTOIMMUNE THYROID DISEASESAUTOIMMUNE THYROID DISEASES
Hashimoto’s thyroiditisHashimoto’s thyroiditis
Idiopathic MyxoedemaIdiopathic Myxoedema
Asymptomatic thyroiditisAsymptomatic thyroiditis
Endocrine exophthalmusEndocrine exophthalmus Grave’s diseaseGrave’s disease
Type 1 DMType 1 DMHirata’s syndromeHirata’s syndrome
Premature ovarian failurePremature ovarian failureLymphocitic hypophysitisLymphocitic hypophysitis
NeurohypophysitisNeurohypophysitis
Atrophic gastritisAtrophic gastritisPernicious anemiaPernicious anemia
Coeliac diseaseCoeliac disease
Chronic inflamm.Chronic inflamm.bowel diseasesbowel diseases
Autoimmune hepatitisAutoimmune hepatitisPrimary biliary cirrhosisPrimary biliary cirrhosisSclerosing cholangitisSclerosing cholangitis
VitiligoVitiligoAlopeciaAlopecia
AutoimmuneAutoimmunethrombocytopeniathrombocytopenia
Autoimmune hemol. anemiaAutoimmune hemol. anemiaAnti-phospholipid syndromeAnti-phospholipid syndrome
Miastenia gravisMiastenia gravisStiff-mann syndromeStiff-mann syndrome
Multiple sclerosisMultiple sclerosis
LESLESLEDLED
Mixed connectivitisMixed connectivitisRheumatoid arthritisRheumatoid arthritis
Reactive arthritisReactive arthritisSclerodermiaSclerodermia
SSöögren`s syndromegren`s syndrome
VasculitisVasculitis
++ ++ ++ ++
EndocrineEndocrineDiseasesDiseases
3 A3 A
GastrointestinalGastrointestinalApparatusApparatus
3 B3 B
SkinSkin/ Hemopoietic/ Hemopoieticsystem/ Nervous systemsystem/ Nervous system
3 C3 C
Collagen Diseases/Collagen Diseases/VasculitisVasculitis
3 D3 D
Erythema dyschromicum perstans, 1961Erythema dyschromicum perstans, 1961Oswaldo Ramiretz, San Salvador, 1957Oswaldo Ramiretz, San Salvador, 1957
Los cenicientos, Ashy dermatosisLos cenicientos, Ashy dermatosis Epidemiology
predominantly III-VI Fitzpatrick skin type slightly higher incidence in women peak 2nd and 3rd decades
Etiology: intestinal whipworm infection endocrine disorders (thyroid disease) radiographic contrast media ammonium nitrate ingestion occupational cobalt allergy chronic hepatitis C HIV infection exposure to chlorothalonil – fungicide in banana plantation
Marion Sulzberg1895–1983
Dermatology for skin of color, A. Kelly, S. Taylor, 2009, p. 167
Genetic susceptibility Aberrant immune response targeting basal cell layer
antigens Abnormal cell mediated immunity Increased expression of intercellular adhesion molecule
1 and MHC class II (HLA-DR4) within the basal cell layer
Ia antigen expression of keratinocytes OKT5 and OKT6 staining of Langerhans’ cells Presence of thrombospondin receptor CD36 Cellular dermal infiltrate express CD69 and cytotoxic cell
marker CD94
Erythema dyschromicum perstansErythema dyschromicum perstans
Pathogenesis
Discussion Lichen planus pigmentosus Lichen planus actinicus Postinflammatory hyperpigmentation
Dermatology for skin of color, A. Kelly, S. Taylor, 2009, p. 167Erythema dyschromicum perstans, R. Schwarz, MD; Chief Editor: Dirk M Elston, MD
EDP spares oral, genital mucosa, scalp, nails, palms, soles
DiscussionDiscussion
Few cases of Erythema dyschromicum perstans & vitiligo in the same patient
Darker skin HLA-DR4 association A Gross et all, Source Institute of
Biomedicine, Caracas, Venezuela
Predominance of cytotoxic T-cell Ia antigen positivity Increased Langerhans cells in epidermis
Erythema dyschromicum perstans and vitiligo, Narayan S Naik MD, Dermatology Online Journal 9(4): 25 From the Ronald O. Perelman Department of Dermatology, New York University Mononuclear cell subpopulations and infiltrating lymphocytes in erythema dyschromicum perstans and vitiligo. Gross A, Tapia FJ, Mosca W, PerezRM, Briceño L, Henriquez JJ, Convit J.SourceInstitut of Biomedicine, Caracas, Venezuela.
Alter immuneregulation
TRICHROME VITILIGO VULGARIS&
GRAVE’S DISEASE&
ERYTHEMA DYSCHROMICUM PERSTANS
Immune cellparticipation
Autoimmunepathogenesis
ConclusionConclusion
Thank you for your attentionThank you for your attention!!