T cell diseases of the skin Flashcards
1
Q
Skin homing T cell antigens
A
- CCR4
- CLA
2
Q
Lung homing T cell antigens
A
- VLA-1
3
Q
Gut homing T cell antigens
A
- α4β7 integrin
- CCR9
4
Q
TRM phenotype
A
- Accumulate in barrier tissues following T cell activation in these tissues
- Persist in these tissues and confer antigen-dependent protection
- Sessile and non-recirculating
5
Q
There are ___ memory T cells residing in every square cm of skin
A
There are 1 million memory T cells residing in every square cm of skin
6
Q
The population of resident T cells within skin is ___% of the circulating human T cell population.
A
The population of resident T cells within skin is 200% of the circulating human T cell population.
7
Q
Local skin infection leads to the seeding of ___ with TRMs specific for antigens of the infectious agent.
A
Local skin infection leads to the seeding of the local area to a high degree and the total skin surface to a lower degree with TRMs specific for antigens of the infectious agent.
8
Q
TRM and skin-tropic TCM give rise to distinct ____
A
TRM and skin-tropic TCM give rise to distinct inflammatory lesions in the skin
9
Q
Inflammatory skin diseases caused by TRM
A
Psoriasis and mycosis fungoides
10
Q
Cutaneous T cell lymphomas
A
- aka CTCLs
- Heterogeneous collection of non-Hodgkin’s lymphomas derived from skin-trafficking T cells
- Mycosis fungoides and Sezary syndrome are most common
- MF has a good prognosis, Sezary syndrome patients often do not live past 3-4 years of diagnosis without hematopoietic stem cell transplant. This is because MF is skin-limited while Sezary syndrome has systemic symptoms in lymphatics and blood
- MF is a malignancy of TRMs, SS is a malignancy of TCMs
11
Q
Mycosis fungoides
A
- Skin-limited CTCL, malignancy of intradermal TRMs
- Survival decreases with progression of skin lesions from patches, to plaques, to tumors
- Treatment is palliative, not curative
- Most lesions have some pruritis, ranging from little to severe
12
Q
Early mycosis fungoides is often mislabeled as ___.
A
Early mycosis fungoides is often mislabeled as atypical psoriasis or eczema.
13
Q
How do you tell early MF apart from other skin diseases?
A
- Lesions often irregular in shape
- peculiar in color (reddish brown, violaceous, or orange)
- asymmetric in distribution
- May be slightly scaled in patch-phase
- Sometimes manifests as poikiloderma
- Lymphadenopathy found in advanced disease
- Skin biopsy is crucial to diagnose
14
Q
A
Mycosis fungoides
15
Q
A
Mycosis fungoides
16
Q
Histopathologic findings of mycosis fungoides
A
- Pautrier’s microabscesses within the epidermis (microabscesses of lymphocytes, often atypical lymphocytes)
- Lymphocytic inflammation in the dermis, often with atypical lymphocytes
- Lymphocytes with convoluted, cerebriform nuclei
-
Oligoclonality of T cells
*
17
Q
The TRMs involved in mycosis fungoides are ___.
A
The TRMs involved in mycosis fungoides are usually CD4, but sometimes CD8.
18
Q
Treatment of mycosis fungoides
A
- Topical steroids (in early disease)
- UV light (UVA or UVB) in combination with psoralens
- Topical agents such as nitrogen mustard or topical retinoids
- Electron beam therapy
- Low dose irradiation
- Chemotherapy for systemic disease
19
Q
Sezary syndrome
A
- aka leukemic CTCL
- Triad of: complete erythema, generalized lymphadenopathy, and abnormal T cells in the skin
- T cell oligoclonality, CD4/CD8 ratio >10, absolute Sezary cell count at least 1,000 per microliter
- May cause marked exfoliation
- Edema, lichenification, pruritis, diffuse scaling
- Lymphadenopathy, alopecia, onychodystrophy and palmoplantar hyperkeratosis common findings
20
Q
Sezary cell
A
21
Q
Differential for Sezary syndrome
A
- May be difficult to distinguish from non-malignant forms of erythroderma
- Psoriatic erythroderma at top of list
- Atopic dermatitis or other dermatitis (irritant, contact)
- pityriasis rubra pilaris
- drug eruption (TEN)
- idiopathic erythroderma
22
Q
A
Sezary syndrome
23
Q
Histopathology of Sezary syndrome
A
- Epidermotropism of MF often absent in Sezary syndrome
- In up to 1/3 patients, histopathologic findings nonspecific
- Involved lymph nodes characteristically show a dense, monotonous infiltrate of Sézary cells and disturbance of normal architecture
- Neoplastic T cells have a mature CD3 + , CD4 + , CD8 – phenotype and characteristically lack CD7 and CD26 expression
24
Q
Treatment of Sezary syndrome
A
- Being a leukemia, systemic treatment is required by definition
- alemtuzumab (anti-CD52) is a T cell depleting agent that is quite effective, full remission in 50% of patients, response rate 100%
- Most other treatments <30% response rate
- extracorporeal photopheresis
- Systemic IFN-α or IFN-γ therapy
- systemic retinoids, methotrexate, HDAC inhibitors and chemotherapy regimens
- In all patients with Sézary syndrome, a definitive cure requires stem cell transplantation.
25
Extracorporeal photophoresis
* White blood cells are removed from the patient several hours after psoralen ingestion, are externally exposed to UVA, and reinfused into the circulation
* Its mechanism of action remains unclear but it appears to involve the generation of tolerogenic dendritic cells and increasing numbers of regulatory T cells.
26
Wood's light
Special frequency of light which accentuates depigmented skin. Used to help visualize vitiligo and other depigmenting skin diseases.
27
White spots should be examined for:
* Partial versus complete pigment loss
* Presence of absence of scale
28
Differential for white spots on skin
* Post-inflammatory hypopigmentation
* Vitiligo
* Tuberous sclerosis
* Tinea versicolor
* Pityriasis alba
Of these, only vitiligo results in **complete** loss of pigment from lesions, and **only tinea versicolor and pityriasis alba are associated with scale.**
29
Vitiligo key clinical features
* Wood's light accentuates completely depigmented macules without scale
* Commonly seen in periorificial and dorsal hands, elbows, and knees
* Vitiligo is a common cause of depigmentation
30
Vitiigo
* Aquired autoimmunity against self melanocytes, resulting in depigmentation in non-scaling patches
* 1% prevalence, incidence highest in 10-30 y.o. group
* Otherwise asymptomatic, but often medical attention is sought to avoid cosmetic disfigurement
*
31
Macules of vitiligo are ___ in shape.
Macules of vitiligo are **round or oblong** in shape.
32
Vitiligo may affect. . .
* Any area of skin or mucous membrane
* Most common over extensor bony surfaces and periorificial areas
* Involvement of hairy areas may result in depigmentation of hair
33
Vitiligo involving the hair follicles of the eyelash
34
Classification of vitiligo
* Localized vitiligo
* Focal : one or more macules in one area, but not clearly in a segmental distribution
* Unilateral/segmental : one or more macules involving a unilateral segment of the body, usually stop at midline
* Mucosal : mucous membranes alone
* Generalized vitiligo
* Vulgaris : scattered patches that are widely distributed
* Acrofacial : distal extremities and face
* Mixed : various combinations of segmental, acrofacial and/or vulgaris
* Universal vitiligo
* Complete or nearly complete depigmentation
35
Vitiligo chart
36
\_\_% of vitiligo patients have generalized vitiligo
**90%** of vitiligo patients have generalized vitiligo
37
Autoimmune diseases associated with vitiligo
* Grave's disease
* Pernicious anemia
* Addison's disease
38
Histopathology of vitiligo
* Loss of melanocytes in affected areas (may require special stains to appreciate)
39
Pathology of vitiligo
Three potential etiologies
1. Autoimmune (driven by CD8 T cells and IFNg. Anti-IFNg therapies reverse pathology in these cases)
2. Neural (Neurochemical mediators driving melanocyte apoptosis. Known to be the true etiology for many cases of disease)
3. Self-destruction (due to intrinsic defects in the melanocytes or due to defective defense against oxidative stress leading to destruction of melanocyte)
40
Treating vitiligo
* No cure, but there are treatments to slow down or halt progress
* Topical, high-potency steroids effective in some patients
* Topical macrolides also effective without steroid downsides
* UVB therapy recommended for widespread vitiligo (308 nm narrow-band UVB therapy ideal)
* Skin grafting from unaffected area
* Melanocyte isolation, culture, and re-introduction is in trial right now
* Covermark and Dermablend are cosmetics which are designed to cover vitiligo patches and blend in with unaffected skin
* In selected individuals, depigmentation of remaining pigmented skin may be the therapy of choice. This is done with 20% benoquin. It is irreversible, so the patient must be SURE
* Type II IFN and JAK inhibitor studies currently underway, early results positive
41
The course of vitiligo is \_\_\_.
The course of vitiligo is **unpredictable**.
42
\_\_\_ may occur in cases of chronic vitiligo.
**Spontaneous repigmentation** may occur in cases of chronic vitiligo.
Although, it is often incomplete
43
Most concerning aspect of vitiligo
* Social stigma and body image
* particularly deeply pigmented patients may suffer social stigmatization
* In some cultures, vitiligo has been confused with the white spots of leprosy and has resulted in social ostracism
44
Key features of alopecia areata
* Form of autoimmunity
* Acute onset of well-circumscribed, oval patches of non-scarring alopecia
* No gender preference, onset typically early adulthood
45
Alopecia areata
46
Alopecia areata association with other autoimmune diseases
* 25% of patients have another form of autoimmunity
* Type 1 diabetes common comorbidity
* Grave's disease
* vitiligo
47
Concordance rate for alopecia areata
55%
Suggests powerful genetic influence, but also important environmental/developmental factors
48
Non-autoimmune associations with alopecia areata
* Atopic dermatitis the single most common comorbidity
*
49
Anatomy of pilosebaceous unit
50
Physical examination of alopecia areata
* Well-circumscribed, round or ovoid patches
* Sometimes erythema and slight tenderness
* Subsequent slight depression of scalp and studding with exclamation point hairs
* Eyebrows, eyelashes, beard, and other body hair may also be affected
* Fine stripping or pitting of nails also associated
51
alopecia totalis
loss of all scalp hair
52
alopecia universalis
Loss of all body hair
53
Differential for alopecia
* Alopecia areata
* Secondary syphilis
* Trichotillomania (Ill-marginated,
irregular patches of alopecia containing the stubble of broken hairs are typical)
* Fungal infection (usually assc. with redness and scale)
54
Histopathology of alopecia areata
* presence of small, dystrophic hair structures
* lymphocytic infiltrate surrounds the early anagen hair bulbs
55
Normal anagen hair follicle keratinocytes typically lack expression of . . .
. . . both Class I and Class II MHC! Suggests immunologic privilege of the human hair follicle bulb
56
Treatment of alopecia
* There is no cure
* For local lesions, topical potent steroids or intralesional injection of triamcinolone sometimes effective
* immunotherapy by induction of allergic contact dermatitis
* Phototherapy
* topical minoxidil
* oral cyclosporine
* Novel strategies are inhibition of JAKs and induction of CTLA-4
57
Course of alopecia areata
* Large areas/long duration (\>1 year) associated with poor prognosis
* Overall though, variable and unpredictable
* Most patients with localized disease have spontaneous recovery. However, relapses are not uncommon
58
TRM vs TCM on flow
59
Tinea versicolor
Fungal infection. A common cause of pigment loss
