T cell diseases of the skin Flashcards
Skin homing T cell antigens
- CCR4
- CLA
Lung homing T cell antigens
- VLA-1
Gut homing T cell antigens
- α4β7 integrin
- CCR9
TRM phenotype
- Accumulate in barrier tissues following T cell activation in these tissues
- Persist in these tissues and confer antigen-dependent protection
- Sessile and non-recirculating
There are ___ memory T cells residing in every square cm of skin
There are 1 million memory T cells residing in every square cm of skin
The population of resident T cells within skin is ___% of the circulating human T cell population.
The population of resident T cells within skin is 200% of the circulating human T cell population.
Local skin infection leads to the seeding of ___ with TRMs specific for antigens of the infectious agent.
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.
TRM and skin-tropic TCM give rise to distinct ____
TRM and skin-tropic TCM give rise to distinct inflammatory lesions in the skin
Inflammatory skin diseases caused by TRM
Psoriasis and mycosis fungoides
Cutaneous T cell lymphomas
- 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
Mycosis fungoides
- 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
Early mycosis fungoides is often mislabeled as ___.
Early mycosis fungoides is often mislabeled as atypical psoriasis or eczema.
How do you tell early MF apart from other skin diseases?
- 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
Mycosis fungoides
Mycosis fungoides
Histopathologic findings of mycosis fungoides
- 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
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Oligoclonality of T cells
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The TRMs involved in mycosis fungoides are ___.
The TRMs involved in mycosis fungoides are usually CD4, but sometimes CD8.
Treatment of mycosis fungoides
- 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
Sezary syndrome
- 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
Sezary cell
Differential for Sezary syndrome
- 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
Sezary syndrome
Histopathology of Sezary syndrome
- 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
Treatment of Sezary syndrome
- 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.
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.
Wood’s light
Special frequency of light which accentuates depigmented skin. Used to help visualize vitiligo and other depigmenting skin diseases.
White spots should be examined for:
- Partial versus complete pigment loss
- Presence of absence of scale
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.
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
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
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Macules of vitiligo are ___ in shape.
Macules of vitiligo are round or oblong in shape.
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
Vitiligo involving the hair follicles of the eyelash
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
Vitiligo chart
__% of vitiligo patients have generalized vitiligo
90% of vitiligo patients have generalized vitiligo
Autoimmune diseases associated with vitiligo
- Grave’s disease
- Pernicious anemia
- Addison’s disease
Histopathology of vitiligo
- Loss of melanocytes in affected areas (may require special stains to appreciate)
Pathology of vitiligo
Three potential etiologies
- Autoimmune (driven by CD8 T cells and IFNg. Anti-IFNg therapies reverse pathology in these cases)
- Neural (Neurochemical mediators driving melanocyte apoptosis. Known to be the true etiology for many cases of disease)
- Self-destruction (due to intrinsic defects in the melanocytes or due to defective defense against oxidative stress leading to destruction of melanocyte)
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
The course of vitiligo is ___.
The course of vitiligo is unpredictable.
___ may occur in cases of chronic vitiligo.
Spontaneous repigmentation may occur in cases of chronic vitiligo.
Although, it is often incomplete
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
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
Alopecia areata
Alopecia areata association with other autoimmune diseases
- 25% of patients have another form of autoimmunity
- Type 1 diabetes common comorbidity
- Grave’s disease
- vitiligo
Concordance rate for alopecia areata
55%
Suggests powerful genetic influence, but also important environmental/developmental factors
Non-autoimmune associations with alopecia areata
- Atopic dermatitis the single most common comorbidity
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Anatomy of pilosebaceous unit
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
alopecia totalis
loss of all scalp hair
alopecia universalis
Loss of all body hair
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)
Histopathology of alopecia areata
- presence of small, dystrophic hair structures
- lymphocytic infiltrate surrounds the early anagen hair bulbs
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
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
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
TRM vs TCM on flow
Tinea versicolor
Fungal infection. A common cause of pigment loss
