Seborrheic dermatitis is a scaly dermatitis on the scalp (dandruff) and face.
 - due to Pitysporium species
 - can be seen in AIDS as an opportunistic infection

Autoimmune Diseases
These are a group of disease where antibodies  (or CMI) are produced against self antigens, causing disease process.

Normally one's immune competent cells do not react against one's own tissues. This is due to self tolerance acquired during embryogenesis. Any antigen encountered at that stage is recognized as self and the clone of cells capable of forming the corresponding antibody is suppressed.

Mechanism of autoimmunity

(1) Alteration of antigen

-Physicochemical denaturation by UV light, drugs etc. e.g. SLE.
- Native protein may turn antigenic  when a foreign hapten combines with it, e.g. Haemolytic anemia with Alpha methyl dopa.

(2) Cross reaction: Antibody produced against foreign antigen may cross react with native protein because of partial similarity e.g. Rheumatic fever.

(3) Exposure of sequestered antigens: Antigens not normally exposed to immune competent cells are not accepted as self as tolerance has not been developed to them. e.g. thyroglobulin, lens protein, sperms.

(4) Breakdown of tolerance : 
Emergence of forbidden clones (due to neoplasia of immune system as in lymphomas and lymphocytic leukaemia)
Loss of suppressor T cells as in old age and CMI defects

Autoimmunity may be
Organ specific.
Non organ specific (multisystemic)

I. Organ specific

(1) Hemolytic anaemia:

Warm or cold antibodies (active at 37° C or at colder temperature)
They may lyse the RBC by complement activation or coat them and make them vulnerable to phagocytosis

(2) Hashimoto's thyroiditis:
 
Antibodies to thyroglobulin and microsomal antigens.
Cell mediated immunity.
Leads to chronic. destructive thyroiditis.

(3) Pernicious anemia

Antibodies to gastric parietal cells and to intrinsic factor.

2. Non organ specific.

Lesions are seen in more than one system but principally affect blood vessels and
connective tissue (collagen diseases).

1. Systemic lupus erythematosus  (SLE). Antibodies to varied antigens are seen. Hence it is possible that there is abnormal reactivity of the immune system in self recognition.

Antibodies have been demonstrated against:

Nuclear material (antinuclear I antibodies) including DNA. nucleoprotein etc. Anti nuclear antibodies are demonstrated by LE cell test.
Cytoplasmic organelles- mitochondria, rib osomes, Iysosomes.
Blood constituents like RBC, WBC. platelets, coagulation factors.

Mechanism. Immune complexes of body proteins and auto antibodies deposit in various
organs and cause damage as in type III hypersensitivity

Organs involved
Skin- basal dissolution and collagen degeneration with fibrinoid vasculitis.
Heart- pancarditis.
Kidneys- glomerulonephritis of focal, diffuse or membranous type 
Joints- arthritis. 
Spleen- perisplenitis and vascular thickening (onion skin).
Lymph nodes- focal necrosis and follicular hyperplasia.
Vasculitis in other organs like liver, central or peripheral nervous system etc,

2. Polyarteritis nodosa. Remittant .disseminated necrotising vasculitis of small and medium sized arteries

Mechanism :- Not definitely known. Proposed immune reaction to exogenous or auto antigens 

Lesion : Focal panarteritis- a segment of vessel is involved. There is fibrinoid necrosis
with initially acute and later chronic inflammatory cells. This may result in haemorrhage
and aneurysm.

Organs involved. No organ or tissue is exempt but commonly involved organs are :
- Kidneys.
- Heart.
- Spleen.
- GIT

3. Rheumatoid arthritis. A disease primarily of females in young adult life. 

Antibodies
- Rheumatoid factor (An IgM antibody to self IgG)
- Antinuclear antibodies in 20% patients.

Lesions

- Arthritis which may progress on to a crippling deformity.
- Arteritis in various organs- heart, GIT, muscles.
- Pleuritis and fibrosing alveolitis.
- Amyloidosis is an important complication.

4. Sjogren's  Syndrome. This is constituted by 

- Kerato conjunctivitis sicca
-Xerostomia
-Rheumatoid arthritis. 

Antibodies

- Rheumatoid factor
- Antinuclear factors (70%).
- Other antibodies like antithyroid, complement fixing Ab etc
- Functional defects in lymphocytes. There is a higher incidence of lymphoma

5. Scleroderma (Progressive systemic sclerosis)
Inflammation and progressive sclerosis of connective tissue of skin and viscera.

Antibodies

- Antinuclear antibodies.
- Rheumatoid factor. .
- Defect is cell mediated.

lesions

Skin- depigmentation, sclerotic atrophy followed by cakinosis-claw fingers and mask face.
Joints-synovitis with fibrosis
Muscles- myositis.
GIT- diffuse fibrous replacement of muscularis resulting in hypomotility and malabsorption
Kidneys changes as in SLE and necrotising vasculitis.
Lungs – fibrosing alveolitis.
Vasculitis in any organ or tissue.

6.Wegener’s granulomatosis. A complex of:
Necrotising lesions in upper respiratory tract.
Disseminated necrotising vasculitis.
Focal or diffuse glomerulitis.

Mechanism. Not known. It is classed with  autoimmune diseases because of the vasculitis  resembling other immune based disorders.
 

Eczematous Dermatitis
Eczematous dermatitis includes a large category of skin lesions characterized by severe pruritus and distinctive gross and microscopic features.
 - type I hypersensitivity is involved with atopic dermatitis in patients who have an allergic history.
 - type IV hypersensitivity is involved in contact dermatitis (poison ivy).
 - acute eczematous dermatitis is characterized by a weeping, pruritic rash, while a chronic eczematous dermatitis presents with dry, scaly, plaque-like thickening of the skin, a process called lichenification.  

AMYLOIDOSIS

Definition. Extra cellular  deposition of an eosinophilic hyaline homogenous material in Various organs, occurring in a variety of clinical  states.

Staining reactions

Iodine :- Brown, turning blue on addition of H2SO4 (gross and microscopic Stain).
P.A.S. – Positive  (Magenta pink).
Congo Red -Orange red which on polarisation gives green birefringence.
Von Geison's –Khaki colour.
Thioflavin T -Yellow fluorescence.

Amyloid is called typical if it given the above staining  reactions Other wise it is termed atypical or para-amyloid.

Classification 

1.    Systemic  amyloidosis associated with underlying disease (secondary),

(A) Chronic infections like 

- Tuberculosis.
- Bronchiectasis.
- Lung abscess.
- Osteomyelitis.
- Syphilis.

(B) Chronic inflammations of varied etiology:

- Rheumatoid arthritis.
- Ulcerative colitis.
- Regional enteritis.
- Lupus erythematosus.

(C) Neoplastic proliferations:

- Of immune system – Multiple myeloma, Hodgkin’s disease.
- Cancers like Renal cell carcinoma etc.

II Systemic primary amyloidosis  with no underlying cause.

III Heredofamilial types.

- Amyloidosis with mediterranean fever.
- Amyloid polyneuropathy.
- Amyloid nephrophathy
- Familial cardiac amyloidosis
- Familial cutaneous amyloid.
- Lattice corneal dystrophy

IV. Localised amyloidosis:

- Senile - in heart, brain, seminal vesicles.
- Amyloidoma of tongue, bronchial tree, skin.
- In islets of Langerhans in Diabetes mellitus.
- In medullary thyroid carcinoma.

Deposition sites
In relation to reticulin  and collagen fibres and to basement, membranes especially
subendothelial. 

Organs involved commonly are : 

Secondary amyloidosis

- Liver.
- Spleen.
- Kidney
- Lymph nodes.
- Adrenals.

Primary amyloidosis

- Heart
- Tongue and gingiva.
- Gastro intestinal tract.
- Lung.
- Wall of small vessels.

Nature and pathogenesis of amyloid
It is primarily made up of protein arranged in two patterns

- There are filaments twisted together to from the fibrils. These chemically resemble light chains of immunoglobulins
- Rods composed of stacked rings. These are made up of alpha globulin components of plasma proteins (P-components)

- In addition to these, extracts of crude amyloid contain  mucopolysacharides complement and gamma globulins.

- Origin of amyloid :- current concept is that it is a direct product of cells of the immune sustem with some abnormality in their immune response

The abnormality may be due to :
- A genetic enzyme defect.
- Prolonged antigenic challenge.
- Neoplastic transformation
- Supression of normal. Response as in induced tolerance.

Neutropenia: Neutropenia is an abnormally low number of neutrophils  
Causes

-Typhoid, paratyphoid. .
-Viral and ricketseal infections.
-Malaria, Kala azar.
-Hypersplenism.
-Aplastic and megaloblastic anaemia.
-Marrow infiltration by malignancies, lymphomas etc.
-SLE.

Gout
This is a disorder caused by the tissue accumulation of excessive amounts of uric acid, an end product of purine metabolism. It is marked by recurrent episodes of acute arthritis, sometimes accompanied by the formation of large crystalline aggregates called tophi & chronic joint deformity. All of these are the result of precipitation of monosodium urate crystals from supersaturated body fluids. Not all individuals with hyperuricemia develop gout; this indicates that influences besides hyperuricemia contribute to the pathogenesis. Gout is divided into primary (90%) and secondary forms (10%). 

Primary gout designates cases in whom the basic cause is unknown or when it is due to an inborn metabolic defect that causes hyperuricemia.

In secondary gout the cause of the hyperuricemia is known.

Pathologic features 

The major morphologic manifestations of gout are
1. Acute arthritis
2. Chronic tophaceous arthritis
3. Tophi in various sites, and
4. Gouty nephropathy

Acute arthritis

- The synovium is edematous and congested,
- There is an intense infiltration of the synovium & synovial fluid by neutrophils.
- Long, slender, needle-shaped monosodium urate crystals are frequently found in the cytoplasm of the neutrophils as well as in small clusters in the synovium.

Chronic tophaceous arthritis:

- This evolves from repetitive precipitation of urate crystals during acute attacks. The urates can heavily encrust the articular surfaces and form visible deposits in the synovium.
- The synovium becomes hyperplastic, fibrotic, and thickened by inflammatory cells, forming a pannus that destroys the underlying cartilage, and leading to erosions of subjacent bone.
- In severe cases, fibrous or bony ankylosis occurs, resulting in loss of joint function. 

Tophi

These are the pathognomonic hallmarks of gout.
- Tophi can appear in the articular cartilage, periarticular ligaments, tendons, and soft tissues, including the ear lobes. Superficial tophi can lead to large ulcerations of the overlying skin.
- Microscopically, they are formed by large aggregations of urate crystals surrounded by an intense inflammatory reaction of lymphocytes, macrophages, and foreign-body giant cells, attempting to engulf the masses of crystals.

Gouty nephropathy

- This refers to the renal complications associated with urate deposition including medullary tophi, intratubular precipitations and renal calculi. Secondary complications such as pyelonephritis can occur, especially when there is urinary obstruction.

Pathogenesis

- Although the cause of excessive uric acid biosynthesis in primary gout is unknown in most cases, rare patients have identifiable enzymatic defects or deficiencies that are associated with excess production of uric acid.
- In secondary gout, hyperuricemia can be caused by increased urate production (e.g., rapid cell lysis during chemotherapy for lymphoma or leukemia) or decreased excretion (chronic renal failure), or both. Reduced renal excretion may also be caused by drugs such as thiazide diuretics, because of their effects on uric acid tubular transport.
- Whatever the cause, increased levels of uric acid in the blood and other body fluids (e.g., synovium) lead to the precipitation of monosodium urate crystals. The precipitated crystals are chemotactic to neutrophils & macrophages through activation of complement components C3a and C5a fragments. This leads to a local accumulation of neutrophils and macrophages in the joints and synovial membranes to phagocytize the crystals. The activated neutrophils liberate destructive lysosomal enzymes. Macrophages participate in joint injury by secreting a variety of proinflammatory mediators such as IL-1, IL-6, and TNF. While intensifying the inflammatory response, these cytokines can also directly activate synovial cells and cartilage cells to release proteases (e.g., collagenases) that cause tissue injury.

- Repeated bouts of acute arthritis, however, can lead to the permanent damage seen in chronic tophaceous arthritis.

b Pseudogout (chondrocalcinosis) (Calcium pyrophosphate crystal deposition disease). Pseudogout typically first occurs in the age 50 years or older. It involves enzymes that lead to accumulation and eventual crystallization of pyrophosphate with calcium. The pathology in pseudogout involves the recruitment and activation of inflammatory cells, and is reminiscent of gout. The knees, followed by the wrists, elbows,
shoulders, and ankles, are most commonly affected. Approximately 50% of patients experience significant joint damage.

Infectious Arthritis can cause rapid joint destruction and permanent deformities. Microorganisms can lodge in joints during hematogenous dissemination, by direct inoculation or by contiguous spread from osteomyelitis or a soft tissue abscess.

Suppurative Arthritis is a subtype of infectious arthritis in which the bacteria seed the joint during episodes of bacteremia. Haemophilus influenzae predominates in children under age 2 years, S. aureus is the main causative agent in older children and adults, and gonococcus is prevalent during late adolescence and young adulthood. 

There is sudden onset of pain, redness, and swelling of the joint with fever, leukocytosis, and elevated ESR. In 90% of nongonococcal suppurative arthritis, the infection involves only a single joint-usually the knee. Joint aspiration is typically purulent, and allows identification of the causal agent.