SICKLE CELL DISEASE

It is an autosomal recessive red blood cell disorder. The manifestations of the disease are primarily related to chronic RBC hemolysis and vaso-occlusive events. Hb is a tetramer composed of 2 alpha globulins and 2 beta type globulins

Alpha chain
2 copies on Ch 16
Expressed from birth throughout life

Beta chain
1 copy on Ch 11
Beta type globulin changes at approximately 6 months

HbS = substitution of valine for glutamic acid as the sixth amino acid of the beta globin chain. Hemoglobin tetramer (alpha2/beta S2) that is poorly soluble when deoxygenated. Deoxygenation or hypoxic states results in the HbS aligning with other HbS molecules. Results in RBC distortion into crescent or sickle shape. Marked decrease in red cell deformability. Results in small vessel vaso-occlusions and chronic hemolytic anemia. SC Disease = homozygosity hemoglobin S (HbS), SC Trait = heterozygous for HbS + HbA (Clinically silent) SC Combined heterozygosity = HbS + different ß-globin mutation (eg. ß thalasemia)
Populations At Risk:
Central African descent, Latin America, India, Middle East, Mediterranean
US:
8-10% of African Americans HbS carriers 0.15% of African Americans born with SCD.
Survival:
Overall survival reduced, but recent improvement with institution of comprehensive careToday, 50% of patients survive beyond 50yo
Causes of Death:
1-3yo: Infection is the leading cause of death10-20yo: Strokes, Acute chest syndrome, Aplastic crisis, Splenic Sequestration crisis

Acute painful episodes, Multiorgan failure, Psychosocial issues, Altered Growth and development, Infections, Bacteremia, Meningitis, Bacterial pneumonia, Osteomyelitis, Cerebrovascular events, Bone complications, Infarction and necrosis, Marrow infarction, Sequestration Crisis, Cardiac complications, Myocardial infarction, Cholelithiasis, Aplastic Crisis, Chronic liver disease, Priapism, Renal complications, Pulmonary complications, Retinopathy

A painful vaso-occlusive crisis is the most frequent clinical symptom of sickle cell disease.

In infants, painful symmetrical swelling of the hands and feet (dactylitis or hand-foot syndrome) caused by infarctions of the small bones may be the initial manifestation of sickle cell anemia.
Most bony vaso-occlusive events occur primarily in the bone marrow cavity. Most are multifocal and associated with mild tenderness and localized edema.
As the child matures, the painful episodes usually affect the joints, especially the hips and knees and those of the chest wall and back. Document the frequency, the precipitants, and the similarity of painful episodes on each visit to exclude more serious causes, such as infection.

Abdominal pain often occurs as excruciating pain with diffuse tenderness, distension, and muscular rigidity of the abdominal wall.
The pain often is caused by small infarcts of the mesentery and viscera, usually without peritoneal signs.
A thorough history, obtained from the patient or the parents, is crucial because their recognition of the nature of the pain helps in distinguishing vaso-occlusive pain from that of other etiologies, such as cholecystitis, perforated viscus, or appendicitis

Sequestration crisis is a distinct form of acute hypersplenism unique to infants and young children.
Vascular occlusion occurs in the splenic sinusoids, resulting in large volumes of blood trapped in the substance of the spleen.
If these events occur gradually, the patient may present with progressive pallor, fatigue, left-sided abdominal pain, and increasing splenomegaly.
This event may occur before or after autoinfarction of the spleen transpires. If splenic sequestration occurs more abruptly, patients may present in extremis, manifesting severe hypovolemic shock.

Promptly evaluate older patients who complain of chest pain, cough, dyspnea, or tachypnea to exclude acute chest syndrome.
The acute febrile pneumonic process is associated with new infiltrates on chest radiographs. Chest pain may precede the radiographic findings, or they may occur with the onset of pain. Although initial chest radiographs may be normal, subsequent radiographs reveal an infiltrate, which may rapidly extend to involve 1 or more lobes and the pleura.
The etiology may be infectious (eg, pneumonia), vaso-occlusive, or both. This syndrome often results in hypoxia and, occasionally, death.

If vascular occlusion occurs in large or small cerebral vessels, a neurologic event may occur. Patients may have gait disturbances, hemipareses, paresthesias, aphasias, altered consciousness, or seizures. MRI findings or high flow on transcranial Doppler sonography of silent lesions are associated with a high risk of strokeInfants and children are susceptible to aplastic anemia crisis.
During episodes of crisis, the degree of anemia worsens, and jaundice decreases due to a profound reticulocytopenia, resulting in no erythrocyte precursors in the bone marrow.
The patient appears acutely ill, tachycardic, and pale, yet nonicteric.
Occasionally, patients recover in several days.
The symptoms are usually due to an infection by the parvovirus B19 prototype.

Infection is a major cause of morbidity and mortality in patients with SCD. Affected children are vulnerable to life-threatening infection as early as four months of age because of splenic dysfunction and the inability of the spleen to filter microorganisms from the blood stream. Splenic dysfunction is followed eventually by splenic infarction, usually by two to four years of age. In the absence of normal splenic function the patient is susceptible to overwhelming infection by encapsulated organisms, especially Streptococcus pneumoniae and Haemophilus influenzae. Particularly susceptible to Salmonella infectionsDysfunctional IgG and IgM antibody responses, defects in alternative pathway fixation of complement, and opsonophagocytic dysfunction may also play a role in the predisposition to invasive infection

LEG ULCER

There are numerous of different types of leg ulcers. The most common are venous ulcers, which are seen in patients with congestive heart failure who cannot pump the blood out of their legs, and it therefore pools and damages the vessels and the surrounding tissue, including the skin. These ulcers are found on the ankles, are brown and irregular.

Cellulitis

Cellulitis and a Poorly Demarcated Red Border

Cellulitis is an infection of the skin with involvement of the subcutaneous tissues. It has poorly demarcated borders, in contrast to erisypelas, which does not go into subcutaneous tissues but is more superficial and has marked swelling of skin with well demarcated borders.
Cellulitis Epidemiology

Cellulitis is more common in men and affects usually the lower extremity. Extremely common in diabetics and patients with suppressed immune systems.

Cellulitis Risk Factors

1.Disruption of cutaneous barrier



Leg ulcer (diabetic or trauma), Traumatic wound, Toe-web intertrigo or fungal infections which can break the skin barrier and lead to ulcerations, Dermatoses such tinea pedis also known as Athlete's foot

2.Previous history of cellulitis

This occurs are there has been prior damage to the skin making it vulnerable to subsequent infection.

3.Venous or lymphatic damage or insufficiency

Venous insufficiency (varicose veins), Overweight (decreased venous return to heart from increased pressure from fat on veins compressing them and leading to stasis), Prior saphenectomy, Prior pelvic radiation or malignancy, Previous tibial fractures, Pregnancy, Filariasis (a parasitic disease in which your lymphatics are damaged and blocked from the parasite).
Cellulitis Microbiology

Cellulitis is usually caused my bacteria that are found on the skin, mainly beta-hemolytic streptococcus, but also Staphylococcus aureus, Pseudomonas if there is a puncture wound, and pasteurella and erysipelothrix if the wound is due to animal contact.
Cellulitis Diagnosis

Most common findings are redness, warmth and tenderness. The hallmarks of inflammation. If these are not present, start looking for something else. Cellulitis is also accompanied with lymphadenopathy and lymphangitis commonly. Abscess may be seen in severely immunocompromised patients or patients presenting with long-standing cellulitis. Systemic features are rare, unless presentation is late, but patients may have fever, chills, and myalgias.

Cultures are usually not sent, because they are often contaminated by commensal bacteria that are not the culprits. Blood and skin cultures however may be sent if there is signs of sepsis, water or animal exposure, recurrent infection, no response to treatments, risk factors for recurrence (lymphedema)


Cellulitis Prognosis

Cellulitis is overall slow to resolve and requires 10-14 days of treatment with antibiotics, usually intravenous.
Cellulitis Treatment

Treatment should be started immediately with empiric antibiotics to cover the most common cultprits, beta-hemolytic Streptococcus and Staphylococcus aureus, Ancef 1-2g IV q8h or Nafcillin 2g IV q4h. Vancomycin is used if there is a severe infection or the infection is associated with dead tissue.
Drug-Resistant Cellulitis

Linezolid, daptomycin, and tigecycline are used.

If the patient is stable, non-toxic, and able to keep their limbs elevated, with guaranteed follow-up and monitoring, then the patient may be treated as an outpatient with oral therapy, Keflex 500 mg po every 6 hours. Clindamycin if allergic to penicillin.
Cellulitis and Immunocompromised Patients

If immunocompromised, treatment is with clindamycin, ceftriaxone, and ciprofloxacin, as polymicrobil coverage is required.

Skin Cosmos

The first identify the skin as a protective coverring for the internal organs was the famous pathologist Rudolph Virchow. It was decades later, that sceintists and physicians began to understand that the skin is a regulated wnvironment of cellular and molecular interactions which react to environmental stimuli.
Keratinocytes

The skin is a mosaic of different cell types. Histologically, the skin is formed by squamous epithelial cells, termed keratinocytes, ass they produce keratin protein. In addition, these cells play a role in protection, as they can produce cytokines, soluble molecules, which can recruit other cells, specifically white blood cells, in times of infection and stress. Melanocytes produce the pigment of our skin, and their proportion varies throughout the races.
Melanocytes

Melanocytes specifically produce melanin, a brown pigment, which they disperse to the lower cells of the skin, basal cells, and with maaturation, these cells move to the surface with the melanin granules in their cytoplasm. Melanin is the molecule which protects us against ultraviolet rays that are found within sunlight.
Langerhans Cells

Langerhans cells are epidermal dendritic cells, which take up foreign particles and present these to our immune system while they traffic to nearby lymph nodes.
Merkel Cells

There is also an extensive network of neural cells and axons within the skin. Merkel cells are believed to have endocrineas well as mechanoreceptor roles within the skin.
Adnexal Structures

Sweat glands play a vital role in body temperature homeostasis. Hair follicles for hair, as well as protecting the skins cell factories, by protecting the stem cells of the skin (the cells with regenerating capacity).

Skin : The Body's Barrier to Infection and Disease

The first identify the skin as a protective coverring for the internal organs was the famous pathologist Rudolph Virchow. It was decades later, that sceintists and physicians began to understand that the skin is a regulated wnvironment of cellular and molecular interactions which react to environmental stimuli.

Keratinocytes
The skin is a mosaic of different cell types. Histologically, the skin is formed by squamous epithelial cells, termed keratinocytes, ass they produce keratin protein. In addition, these cells play a role in protection, as they can produce cytokines, soluble molecules, which can recruit other cells, specifically white blood cells, in times of infection and stress. Melanocytes produce the pigment of our skin, and their proportion varies throughout the races.

Melanocytes
Melanocytes specifically produce melanin, a brown pigment, which they disperse to the lower cells of the skin, basal cells, and with maaturation, these cells move to the surface with the melanin granules in their cytoplasm. Melanin is the molecule which protects us against ultraviolet rays that are found within sunlight.

Langerhans Cells
Langerhans cells are epidermal dendritic cells, which take up foreign particles and present these to our immune system while they traffic to nearby lymph nodes.

Merkel Cells
There is also an extensive network of neural cells and axons within the skin. Merkel cells are believed to have endocrineas well as mechanoreceptor roles within the skin.

Adnexal Structures
Sweat glands play a vital role in body temperature homeostasis. Hair follicles for hair, as well as protecting the skins cell factories, by protecting the stem cells of the skin (the cells with regenerating capacity).