SPIROCHETAL DISEASE

Syphilis

A contagious systemic disease caused by the spirochete Treponema pallidum, characterized by sequential clinical stages and by years of latency.

ACQUIRED SYPHILIS

T. pallidum is a delicate spiral organism about 0.25 µm wide and from 5 to 20 µm long, identified by characteristic morphology and motility with a darkfield microscope or fluorescent techniques

In acquired syphilis, T. pallidum enters through the mucous membranes or skin, reaches the regional lymph nodes within hours, and rapidly disseminates throughout the body. In all stages of disease, perivascular infiltration of lymphocytes, plasma cells, and, later, fibroblasts causes swelling and proliferation of the endothelium of the smaller blood vessels, leading to endarteritis obliterans.

In late syphilis, T. pallidum elicits a granulomatous-like (gummatous) reaction causing masses, ulcerations, and necrosis. Inflammation may subside despite progressive damage, especially in the cardiovascular and central nervous systems.

The CNS is invaded early in the infection. During the secondary stage of the disease, > 30% of patients have abnormal CSF and may have symptoms of meningitis

Symptoms, Signs, and Course

The incubation period of primary syphilis can vary from 1 to 13 wk but is usually from 3 to 4 wk. The disease may present at any stage and long after the initial infection

Primary stage: The primary lesion, or chancre generally evolves and heals within 4 to 8 wk in untreated patients. After inoculation, a red papule quickly erodes to form a painless ulcer with an indurated base that, when abraded, exudes a clear serum containing numerous spirochetes

The regional lymph nodes usually enlarge painlessly and are firm, discrete, and nontender. Chancres occur on the penis, anus, and rectum in men and on the vulva, cervix, and perineum in women. Chancres may also occur on the lips or the oropharyngeal or anogenital mucous membranes.

Secondary stage: Cutaneous rashes usually appear within 6 to 12 wk after infection and are most florid after 3 to 4 mo.

Frequently, generalized, nontender, firm, discrete lymphadenopathy and hepatosplenomegaly are palpable. Over 80% of patients have mucocutaneous lesions, 50% have generalized lymphadenopathy, and about 10% have lesions of the eyes (uveitis), bones (periostitis), joints, meninges, kidneys (glomerulitis), liver, and spleen.

Acute syphilitic meningitis may develop, with headache, neck stiffness, cranial nerve lesions, deafness, and, occasionally, papilledema.

Condyloma lata--hypertrophic, flattened, dull pink or gray papules at the mucocutaneous junctions and in moist areas of the skin--are extremely infectious. Hair often falls out in patches, leaving a moth-eaten appearance (alopecia areata).

Latent stage

In the early latent period (< 2 yr after infection), infectious mucocutaneous relapses may occur, but after 2 yr contagious lesions rarely develop, and the patient appears normal. About 1/3 of untreated persons develop late syphilis

Late or tertiary stage: Lesions may be clinically described as (1) benign tertiary syphilis of the skin, bone, and viscera, (2) cardiovascular syphilis, or (3) neurosyphilis.

The typical lesion is a gumma, an inflammatory mass that evolves to necrosis and fibrosis and that is frequently localized but may diffusely infiltrate an organ or tissue

Benign tertiary syphilis of the bones results in either periostitis with bone formation or osteitis with destructive lesions causing a deep, boring pain, characteristically worse at night. A lump or swelling may be palpable.

Cardiovascular syphilis: A dilated, usually fusiform aneurysm of the ascending or transverse aorta, narrowing of the coronary ostia, or aortic valvular insufficiency usually appears 10 to 25 yr after the initial infection

Neurosyphilis

In meningovascular neurosyphilis, brain involvement is signaled by headache, dizziness, poor concentration, lassitude, insomnia, neck stiffness, and blurred vision. Mental confusion, epileptiform attacks, papilledema, aphasia, and mono- or hemiplegia may also occur

Diagnosis:

Two classes of serologic tests for syphilis (STS) aid in diagnosing syphilis and other related treponemal diseases: screening, nontreponemal tests using lipoid antigens detect syphilitic reagin and include the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR) tests. Specific treponemal tests detect antitreponemal antibodies and include fluorescent treponemal antibody absorption (FTA-ABS) test, microhemagglutination assay for antibodies to T. pallidum (MHA-TP), and Treponema pallidum hemagglutination assay (TPHA).

In darkfield microscopy, light is directed obliquely through the slide so that rays striking the spirochetes cause them to appear as bright, motile, narrow coils against a dark background

Lymphopenia:
Causes

-As part of pancytopenia.
-Steroid administration.

Diseases from Str. pyogenes (Group A strep)

1.  Streptococcal pharyngitis.  Most frequent Group A infection.  Throat has gray-white exudate.  Infection may become systemic into blood, sinuses, jugular vein, meninges.  In less than a week the M-protein and capsule production decrease, and transmission declines.

2.  Skin infections, such as impetigo.  Especially in children.  Different M-proteins than in pharyngitis.  Skin infections associated with edema and red streaking (characteristic).

3.  Necrotizing fasciitis/myositis.  Infection of deeper tissue advances despite antibiotics.

4. Scarlet fever.  Caused by phage-associated erythrogenic toxin-producing strains.  Toxins cause cardiac, renal, and other systemic failures.  Rash is very red with a sand-papery feel and shedding of superficial skin.

5.  Toxic Shock Syndrome.  Parallels the toxic shock caused by TSST-carrying Staph. aureus.

6.  Non-suppurative, post-infection diseases. 

Rheumatic fever (myocarditis, cardiac valve disease, polyarthralgia, rashes.  Occurs two  weeks after a pharyngeal infection)

Glomerulonephritis (Occurs two weeks after pharyngeal or skin infections.  Often due to immunologic reaction to M-protein type 12)

Sickle Cell Disease

Sickle cell anemia is a autosomal recessive genetic disorder. It affects the BETA GLOBIN gene on the CHROMOSOME 16. In sickle cell anemia, the hemoglobin abnormality consists of a point mutation in the beta chain gene for hemoglobin; the resulting abnormal gene product is denoted HbS. If you are heterozygous for the HbS gene you will have what is called sickle trait, which is asymptomatic .

 If you are homozygous for the HbS gene  you will get sickle cell disease, which is symptomatic in most patients.
 The problem with HbS is that as it releases oxygen, it polymerizes and aggregates with other HbS molecules, making the red cell stiff and distorted. These distorted, sickle-shaped red cells are fragile so the patient can end up with a hemolytic anemia.
This can occur as pure disease (homozygous) or trait (heterozygous) or with other haemoglobinopathies. It is common. in Negroes. It is due to Hb-s  which is much less soluble than Hb-A  hence deoxygenation insoluble form  sickling of RBC.

This causes:
•    Removal by RE system. 
•    Blockage of microvessels causing  ischaemia.
 

Roseola
 - alias exanthem subitum; caused by Herpes virus type 6.
 - children 6 months to 2 years old; spring and fall; incubation 10-15 days.
 - sudden onset of a high fever with absence of physical findings; febrile convulsions are particularly common.
 - fever falls by crisis on the 3rd or 4th day → 48 hours after temperature returns to normal macular or maculopapular rash starting on the trunk and spreading centrifugally.

Adult Respiratory Distress Syndrome 
A constellation of pathologic and clinical findings initiated by diffuse injury to alveolar capillaries. This syndrome is associated with a multitude of clinical conditions which primarily damage the lung or secondarily as part of a systemic disorder. 

Pathogenesis 
There are many types of injuries which lead to the ultimate, common pathway, i.e., damage to the alveolar capillary unit. The initial injury most frequently affects the endothelium, less frequently the alveolar epithelium. Injury produces increased vascular permeability, edema, fibrin-exudation (hyaline membranes). Leukocytes (primarily neutrophils) plays a key role in endothelial damage. 

Pathology 
Heavy, red lungs showing congestion and edema. The alveoli contain fluid and are lined by hyaline membranes. 

Pathophysiology 
Severe respiratory insufficiency with dyspnea, cyanosis and hypoxemia refractory to oxygen therapy.