Autoimmune Skin Disease

What is Pemphigus Vulgaris and Foliaceus?

Pemphigus Vulgaris is an autoimmune blistering disorder affecting the intra-epidermal layer of skin
→ causes acantholysis or detachment of keratinocytes from one another by targeting the desmosome proteins

1) Pemphigus Vulgaris is caused by antibodies against desmoglein 1 and/or 3 resulting in the formation of flaccid blisters on the mucosa and skin
→ patients will present with a positive Nikolsky sign where rubbing the skin causes the skin to shear off

2) Pemphigus Foliaceus is a form of pemphigus where there is antibodies against desmoglein 1 and only involves the skin

What are the characteristic histologic features of Pemphigus?

Pemphigus will cause tombstone formation in the epidermis where the keratinocytes form a tombstone shape as they separate from one another
→ will cause a immunofluorescence that lights up and surrounds individual cells

What is Bullous Pemphigoid?

Bullous Pemphigoid is an autoimmune subepidermal (dermal) skin condition that causes the formation of tense blisters and bullae

1) Seen most often in elderly patients that will be extremely itchy and have the formation of these large tense blisters
→ will have a negative nikolsky sign compared to pemphigus

What is Cicatricial Pemphigoid?

Cicatricial Pemphigoid or scarring pemphigoid is a subepidermal autoimmune condition affecting the mucosal surfaces

1) seen along the eye, mouth, etc 

What is the immunofluorescence and histological pattern for bullous and cicatricial pemphigoid

Pemphigoid will have eosinophilic infiltration and immunofluorescence of IgG and C3 along the dermal-epidermal junction

What is paraneoplastic pemphigus?

Paraneoplastic pemphigus is an autoimmune blistering disease that affects the mucosa intradermally
1) Leads to lesions in the mouth that are resistant to therapy as well as lesions along the palms and soles

2) Commonly associated with diseases like
→ non-hodgkin lymphoma
→ chronic lymphocytic leukemia
→ castleman’s disease
→ malignant and benign thymoma
→ Sarcoma
→ Waldenstrom’s macroglobulinemia

What is Dermatitis Herpetiformis?

Dermatitis Herpetiformis is a subepidermal condition associated with celiac disease or thyroid abnormalities

1) Associated with anti-transglutaminase 3 or anti-endomysial antibodies
→ associated with HLA-DQ2 and results in a destruction of villous surface of the small intestine

2) Blisters forming on the elbows, knees, and butt

What are the histological features of dermatitis herpetiformis?

Histology shows neutrophilic papillitis with subepidermal blisters
→ Immunofluorescence will show granular IgA on the papillae or the finger like projections extending from the dermis into the epidermis

What is Systemic Lupus Erythematous?

SLE is an autoimmune connective tissue disease that commonly presents in young middle aged women with a photodistributed malar rash (butterfly rash of the face) and will commonly present with heart issues and renal issues

1) Associated with systemic lupus
→ positive ANA, anti-smith, and ds-DNA antibodies

What is Discoid Lupus Erythematosus?

Discoid Lupus Erythematosus is a form of cutaneous lupus that causes red macules and plaques that will often scar and hyper pigment

1) Discoid Lupus often remains localized to the skin and does not have mucosal involvement
→ may have positive antibodies for ANA and ssDNA 

2) May cause hair loss with scarring on the area where there is hair loss

What is Subacute Cutaneous Lupus?

Subacute Cutaneous Lupus is a form of cutaneous lupus erythematosus that causes red/pink polycyclic annular patches and plaques that occur on sun exposed areas

1) Often occur following usage of a drug like ACE inhibitors and Calcium Channel Blockers

2) Many have joint pain and have positive antibodies associated with systemic lupus

What is Neonatal Lupus?

Neonatal Lupus is a condition affecting children with mothers that have subacute cutaneous lupus or mothers with anti-Ro

1) May cause children to develop permanent heart block, thrombocytopenia, and liver disease
→ classically have polycyclic erythematous plaques

What is the difference between bullous and tumid lupus?

Bullous - blistering

Tumid - deeper down and results in an indentation without changes to the overlying skin

What are the histological changes associated with lupus?

In histological examination, patients with lupus will have superficial and deep lymphocytes in the skin
→ patients also have mucin or a light blue staining around the connective tissue 

What is Dermatomyositis?

Dermatomyositis is a connective tissue disease that can present as amyopathic or inflammatory

1) Can present with or without muscle weakness. When it does have muscle weakness, it has proximal muscle weakness
→ the rashes that dermatomyositis causes are pruritic and may have pink-violet discoloration of the eyelids
→ has photosensitive distribution that is described as having a shawl-like distribution
→ Gottron’s papules or the formation of papules along the joints

2) Often presents with systemic issues like difficulty swallowing and breathing

3) patients with dermatomyositis should be screened for cancer due to the disease being paraneoplastic

What is a useful way to differentiate lupus and dermatomyositis?

Dermatomyositis will have involvement of the joints commonly referred to as gottron’s papules
→ lupus on the other hand has involvement in between the joints 

What is Morphea?

Morphea is localized scleroderma and is a condition that causes excessive collagen production and scarring of the dermis and subcutaneous tissue

1) Morphea leads to pain and disfigurement along with joint dysmotility due to the skin becoming thicker
→ Lacks involvement of internal organ involvement

2) Has several subtypes but is most commonly a plaque, generalized or linear
→ causes the formation of thickened plaques or indurated areas of skin

What is Lichen Sclerosis Atrophicus?

Lichen Sclerosis Atrophicus is a disease that presents with smooth wrinkled soft white patches that often involves the genitals due to loss of collagen in the dermis
→ may have a progressive involvement that leads to scarring of the genitals and can lead to skin cancer

What is Generalized Scleroderma?

Scleroderma can be either generalized or localized

1) Generalized - systemic involvement
→ Fibrosis of the skin due to thickening of the collagen
→ will often have puffy fingers or Raynaud’s phenomenon where there is changes in color of the fingers in response to cold or stress
→ positive for anti-Scl-70 (anti-DNA topoisomerase-I) and anti-RNA polymerase III

What is Limited Scleroderma?

Limited Scleroderma presents as CREST
→ Calcinosis or calcium deposition in the skin
→ Raynaud’s Phenomenon - changing of finger skin color in response to stress or cold
→ Esophageal dysmotility
→ Sclerodactyly - thickening of fingers
→ Telangiectasias

Associated with anticentromere antibodies

What is Raynaud’s?

Raynaud’s Disease is a color change in the digits due to cold or stress
→ Can be primary or secondary to some other condition (like scleroderma)
→ may cause gangrene of the fingers

1) Caused by multifactorial issues leading to vasospasm in the fingers
→ increased alpha 2 activity and elevated endothelian-1

What is the histology of morphea and scleroderma?

Thick collagen

What is Small Vessel Vasculitis

Small Vessel Vasculitis is a finding associated with an autoimmune disease affecting the small vessels. May lead to the formation of erythematous plaques or papules/macules 

1) Classic one is Henoch Schonlein Purpura due to IgA deposition
→ causes purpura and joint pain
→ abdominal pain and renal disease and is commonly seen in children

What is Vitiligo?

Vitiligo is depigmented white patches caused by autoimmune destruction of melanocytes via autoreactive CD8 T-cells

What is Alopecia Areata?

Alopecia is an autoimmune condition against the hair
→ is non-scarring and is identifiable through new hair growth with exclamation point hairs
→ has bald patches in the hair

Causes inflammation around the hair follicles