Lymphopenia:
Causes

-As part of pancytopenia.
-Steroid administration.

Rickettsial Diseases

Epidemic Typhus

An acute, severe, febrile, louse-borne disease caused by Rickettsia prowazekii, characterized by prolonged high fever, intractable headache, and a maculopapular rash.

Symptoms, Signs, and Prognosis

After an incubation period of 7 to 14 days, fever, headache, and prostration suddenly occur. Temperature reaches 40° C (104° F) in several days and remains high, with slight morning remission, for about 2 wk. Headache is generalized and intense. Small pink macules appear on the 4th to 6th day, usually in the axillae and on the upper trunk; they rapidly cover the body, generally excluding the face, soles, and palms. Later the rash becomes dark and maculopapular; in severe cases, the rash becomes petechial and hemorrhagic. Splenomegaly occurs in some cases. Hypotension occurs in most seriously ill patients; vascular collapse, renal insufficiency, encephalitic signs, ecchymosis with gangrene, and pneumonia are poor prognostic signs. Fatalities are rare in children < 10 yr, but mortality increases with age and may reach 60% in untreated persons > 50 yr.

Seborrheic keratosis
1. A round, brown-colored, flat wart.
2. Most often seen in middle-aged to older adults.
3. A benign lesion.

Avitaminoses -  Vitamin deficiencies are more commonly secondary disorders associated with malabsorption conditions and chronic alcoholism.

A. Vitamin A - (retinoids, fat soluble compounds derived from ß-carotene) The best-known effect of deficiency is an inability to see in weak light (night blindness due to decreased rhodopsin).
-> The pathology is also characterized by skin lesions (rash on the extremities with punctate erythematous lesions). In malnourished children, vitamin A supplements reduce the incidence of infections such as measles, even in children without signs of preexisting deficiency.

B. Vitamin D - (1, 25 OH2 D3) Deficiency produces osteomalacia (called rickets in children). Many of the effects of osteomalacia overlap with the more common osteoporosis, but the two disordersare significantly different.
-> The specific alteration in osteomalacia and rickets is a failure of mineralization of the osteoid matrix resulting in decreased appositional bone growth. 

C. Vitamin E - Very rare. Occurs as a secondary disorder in conditions associated with fat maladsorption such as cystic fibrosis, pancreatitis, and cholestasis (bile-flow obstruction).
-> Vitamin E deficiency causes a neurological disorder characterized by sensory loss, ataxia and retinitis pigmentosa due to free radical mediated neuronal damage.

D. Vitamin K - (phylloquinone) Present in most leafy plants and also synthesized by intestinal bacteria. Vitamin K is required for the production of specific clotting factors and a deficiency is characterized by impaired coagulation (elevated clotting times). Although this can occur in newborns that are given breast milk low in vitamin K, the deficiency is almost always secondarily associated with the use of certain anti-coagulants or disorders such as obstructive jaundice, celiac, or pancreatic disease.

 E. Thiamine - (B1) The deficiency is known as beriberi. Thiamine deficiency is characterized by a peripheral neuropathy that affects sensation particularly in the legs (associated with demyelination of peripheral nerves), in more severe cases Korsakoff syndrome (neuropathy characterized by impaired ocular motility, ataxia, and mental confusion) and cardiomyopathy can occur.

F. Nicotinamide (niacin) - The deficiency is known as pellagra. Primary deficiencies are associated with diets that consist primarily of a single low quality protein source (i.e. corn). It results most commonly as a complication of alcoholism.

-> The pathology is characterized by hyperkeratosis and vesiculation of skin, atrophy of the tongue epithelium, and a neuropathy that can affect cortex and peripheral neurons.

- Initial symptoms include a smooth, red tongue, a sore mouth, and ulceration of the inside of the cheeks.

- The skin on the neck, chest, and back of the hands may become brown and scaly. 

- Often there is nausea, vomiting, and diarrhea. There may also be insomnia, depression, confusion, and rapid changes of mood. Long-standing pellagra can result in dementia and death.

G. Vitamin B12 - (cobalamin) Because cobalamin is synthesized by intestinal bacteria and is widely available in many foods, deficiencies are almost always secondary disorders associated with gastric atrophy (and decreased uptake via intrinsic factor), microbial proliferation (AIDS), long-term antacids, chronic alcoholism, idiopathic (age-related).

In addition to anemia, the primary clinical symptoms include a sensory neuropathy (polyneuropathy), sclerosis of the spinal cord and atrophy of some mucous tissues.

H. Vitamin C - (ascorbic acid) The classic deficiency is known as scurvy. The essential pathology involves an inability to produce mature collagen and hence affects connective tissue.

This is characterized by an inability to synthesize osteoid and dentin (and results in decreased wound healing) and a loss of integrity of blood vessel walls.

Oral lesions are only a feature of the advanced form of the disease; early signs include fatigue, dermatitis, and purpura. There can be abnormalities in the growing bones of infants. 

I. Vitamin B6 - (Pyridoxine) A deficiency can lead to peripheral neuropathy, most commonly associated with multivitamin B deficiencies in malnutrition and alcoholism. 

V. Major Minerals - Sodium, potassium, chlorine, and magnesium are required for life but dietary deficiencies do not develop.
A. Iodine - Essential for the synthesis of thyroid hormones, and severe iodine deficiency is  associated with hypothyroidism. The compensatory activity of the thyroid gland causes a  characteristic enlargement called goiter.

B. Calcium - Required for bone mineralization, the RDA for adults is 800 mg/day. Clinical trials have shown that 1000-2000 mg/day can delay the bone loss observed in the elderly and decrease the risk of osteoporosis. See also section IV B.

VI. Trace Elements - At least 10 elements (examples: Co, Mn, Si) are required in minute amounts for normal development and metabolism.

A. Zinc - A deficiency can result from inadequate amounts given during total parenteral nutrition or as a secondary effect of acrodermatitis enteropathica (autosomal recessive trait characterized by alopecia, dermatitis, and diarrhea - the disease responds to administration of zinc).

B. Copper - Deficiencies are rare and primarily associated with malabsorption syndromes and total parenteral nutrition. Copper is required for normal hematopoiesis and bone growth. A deficiency resembles iron deficiency anemia and osteoporosis.

C. Fluoride - Levels in drinking water greater than 1 ppm cause mottling of teeth and in areas with chronic naturally induced fluorosis there is abnormal calcification of ligaments and tendons.

Fungal
 
Superficial mycoses

1. Superficial mycoses→outermost layers of the skin or its appendages; skin, nails and/or hair.
2. Dermatophytoses transmitted by contact with man (anthropophilic; weak inflammatory response), animals (zoophilic; brisk inflammatory response), or contact with soil (geophilic; strongest inflammatory response).
3. Trichophyton→hair, skin, or nails; Microsporum → hair and skin; and Epidermophyton→skin alone.
4. The diagnosis is best made by culture of skin scrapings secured from the leading edge of the lesion.
 - use Wood's light to check for fluorescing metabolites.
 - direct KOH preparations of the scraped material
 
 Subcutaneous Mycoses
 
1. Subcutaneous mycoses are usually related to traumatic implantation into the skin.
2. Chromoblastomycosis, or verrucous (wart-like) dermatitis, is a chronic skin lesion associated with several pigmented fungi (Fonsecaea, Phialophora, and Cladosporium).
 - granulomatous reaction in subcutaneous tissue are pigmented, thick walled bodies are visible in tissue section.
3. Mycetomas (maduromycosis) are characterized by a localized, tumorous nodule (usually foot) that occurs in response to chronic progressive destruction of skin, subcutaneous tissue, fascia, muscle and bone 

4. Sporotrichosis is caused by the dimorphous fungus, Sporothrix schenckii.
 - traumatic implantation of the fungus growing in soil, thus the association with "rose gardeners disease".
 - MC lymphocutaneous disease → painless nodule at inoculation site → chain of suppurating subcutaneous nodules that drain to the skin surface along the course of the lymphatics.

- cigar shaped yeast forms are seen in the suppurative nodules and asteroid bodies (Splendore-Hoeppi phenomenon) are noted within granulomatous microabscesses.
 - treatment: oral potassium iodide

Characteristics of Immunoglobulin subclasses

I. Ig G:

(i) Predominant portion (80%) of Ig.

(ii) Molecular weight 150, 000

(iii) Sedimentation coefficient of 7S.

(iv) Crosses placental barrier and to extra cellular fluid.

• (v) Mostly neutralising effect. May be complement fixing.

(vi) Half life of 23 days.

2.IgM :

(i) Pentamer of Ig.

(ii) Molecular weight 900, 000

(iii) 19S.

(iv) More effective complement fixation and cells lysis

(v) Earliest to be produced in infections.

(vi) Does not cross placental barrier.

(vii) Halflife of 5 days.

3. Ig A :

• Secretory  antibody. Found in intestinal, respiratory secretions tears, saliva and urine also.
• Secreted  usually as a dinner with secretory piece.
• Mol. weight variable (160,000+)
• 7 S to 14 S.
• Half life of 6 days.

4.Ig D :

• Found in traces.
• 7 S.
• Does not cross placenta.

5. Ig E

• Normally not traceable
• 7-8 S (MoL weight 200,000)
• Cytophilic antibody, responsible for some hypersensitivity states,