obsolete leukocyte-adhesion deficiency syndrome

Leukocyte Adhesion Deficiency Syndrome (LADS): A Rare and Obsolete Condition

Leukocyte adhesion deficiency syndrome (LADS) is a rare and obsolete condition that affects the immune system's ability to fight infections. The syndrome was previously known as leukocyte adhesion deficiency (LAD), but it has been largely replaced by more specific and accurate terminology.

Characteristics of LADS

• Primary immunodeficiency: LADS is a primary immunodeficiency disorder, meaning it is caused by a defect in the immune system itself.
• Adhesion molecule defect: The syndrome results from a defect in adhesion molecules on the surface of white blood cells (leukocytes), which impairs their ability to adhere to and migrate through tissues.
• Recurrent infections: Individuals with LADS are prone to recurrent infections, particularly in soft tissues such as the gums, skin, and muscles.

Types of LADS

There were previously three distinct types of leukocyte adhesion deficiency (LAD), which have since been sub-classified into more specific conditions:

1. LAD1: Characterized by a defect in the CD18 subunit of the integrin molecule.
2. LAD2: Associated with a defect in the fucose-binding protein, leading to impaired leukocyte adhesion and function.
3. LAD3 (also known as LAD-1/variant): This subtype is characterized by a combination of immunodeficiency and bleeding tendency due to a Glanzmann thrombasthenia-like defect.

Treatment and Management

While LADS is an obsolete condition, the treatment and management strategies for its subtypes remain relevant. These include:

• Supportive care: Prophylactic antibiotics and granulocyte transfusions may be used to manage recurrent infections.
• Hematopoietic stem cell transplantation: This is a curative treatment option for some individuals with LADS.
• Gene therapy: Research into gene therapy holds promise for correcting the underlying defect in LADS.

References

[1] [2] [3] [4] [5]

Note: The references provided are based on the context information and may not be up-to-date or accurate.

Recurrent Infections and Poor Wound Healing

Individuals with leukocyte adhesion deficiency (LAD) syndromes, particularly LAD-I, often experience recurrent bacterial infections, including:

• Ear infections
• Skin infections
• Pneumonia
• Omphalitis (infection of the umbilical cord)
• Delayed separation of the umbilical cord

These infections are a result of the impaired ability of white blood cells to migrate to the site of infection or injury. This leads to poor wound healing and increased susceptibility to infections.

Other Symptoms

In addition to recurrent infections, individuals with LAD syndromes may also experience:

• Delayed healing of wounds
• Poor response to antibiotics
• Impaired extravascular leucocyte mobilisation (as seen in LAD-I)
• Severe mental and growth retardations (as seen in LAD-II)

Rare and Obsolete Forms

It's worth noting that some forms of leukocyte adhesion deficiency, such as LAD-III, are extremely rare and have been largely obsolete due to advances in medical understanding and treatment. However, the core symptoms of recurrent infections and poor wound healing remain a hallmark of these conditions.

References:

• [1] Common cutaneous manifestations of LAD include bacterial infections, omphalitis with delayed separation of the umbilical cord, impaired pus formation, and delayed wound healing.
• [3] Patients suffer from recurrent episodes of infections, persistent leukocytosis, and severe mental and growth retardation.
• [4] Leukocyte rolling in postcapillary venules is significantly reduced in LAD patients.
• [9] Common clinical features in leukocyte adhesion deficiency include impaired wound healing, severe periodontal disease, and recurrent widespread pyogenic infections.

Diagnostic Tests for Leukocyte Adhesion Deficiency Syndrome

Leukocyte adhesion deficiency (LAD) syndromes are a group of rare immunodeficiencies characterized by impaired neutrophil adhesion and migration. The diagnosis of LAD syndromes is primarily based on clinical evaluation, patient history, and laboratory tests.

Historical Diagnostic Tests:

In the past, several diagnostic tests were used to identify leukocyte adhesion deficiency syndrome:

• Flow cytometry: This test was used to detect the absence or severe deficiency of adhesive glycoproteins (CD11a, CD11b, CD18) on the surface of white blood cells (WBCs). [1][2]
• Monoclonal antibodies: These were used to detect the presence or absence of specific adhesion molecules on WBCs. [3]
• Complete Blood Count (CBC): A CBC was performed to detect elevated levels of neutrophils and lymphocytes, which is a common finding in LAD syndromes. [4]

Obsolete Diagnostic Tests:

The following diagnostic tests are no longer used for the diagnosis of leukocyte adhesion deficiency syndrome:

• CD11c assay: This test had insufficient analytical sensitivity to allow interpretation of CD11c surface expression and was therefore not useful for diagnosing LAD-1. [5]
• Biopsy: While a skin biopsy may be taken to determine whether white blood cells are present at the infection location, it is no longer considered a primary diagnostic tool for LAD syndromes. [6]

Current Diagnostic Approaches:

The diagnosis of leukocyte adhesion deficiency syndrome now relies on more specific and sensitive tests, including:

• Genetic testing: This is recommended for siblings to identify carriers of the disease-causing mutation.
• Leukocyte Adhesion Deficiency Panel: This panel measures the receptors CD11a, CD11b, CD15s, and CD18 normally found on neutrophils. [7]
• CD11a, CD11b, and CD18 phenotyping: This test is used to aid in the diagnosis of LAD-1 in patients younger than 18 years. [8]

References:

[1] OMIM Entry No: 116920

[2] Flow cytometry for diagnosing leukocyte adhesion deficiency syndrome.

[3] Monoclonal antibodies for detecting adhesion molecules on WBCs.

[4] Complete Blood Count (CBC) for detecting elevated neutrophil and lymphocyte levels.

[5] CD11c assay: insufficient analytical sensitivity.

[6] Biopsy: no longer a primary diagnostic tool.

[7] Leukocyte Adhesion Deficiency Panel for measuring receptor expression on neutrophils.

[8] CD11a, CD11b, and CD18 phenotyping for diagnosing LAD-1 in young patients.

Treatment Options for Leukocyte Adhesion Deficiency (LAD)

Leukocyte adhesion deficiency (LAD) is a rare and serious disorder that affects the immune system's ability to fight infections. While there are no specific treatments that can cure LAD, various medications and therapies can help manage the condition and prevent complications.

Supportive Care

• Prophylactic antibiotics: Regular use of antibiotics to prevent infections (Source: [4])
• Granulocyte transfusions: Transfusions of white blood cells to boost the immune system (Source: [3])

Hematopoietic Stem Cell Transplantation

• This is the only effective treatment for LAD and can be curative (Source: [1], [8])
• Gene therapy, which is under study, appears promising (Source: [1])

Other Therapies

• Fucose supplementation: Correcting the underlying defect in type 2 leukocyte adhesion deficiency with fucose supplementation may be beneficial (Source: [2])
• Tranexamic acid: This antifibrinolytic drug has been used as a long-term prophylaxis, although its effectiveness is unclear (Source: [5])

Management of Infections

• Prompt treatment of infections with antibiotics is essential to prevent complications (Source: [6], [9])
• Hematopoietic cell transplantation represents the only cure for LAD-I, but gene therapy may also be effective (Source: [8])

It's worth noting that these treatments are not specific to obsolete leukocyte-adhesion deficiency syndrome, but rather to Leukocyte Adhesion Deficiency in general.

Based on the provided context, it appears that there are several conditions that can be considered as differential diagnoses for leukocyte adhesion deficiency (LAD) syndromes.

• IRAK-4 deficiency: This is a rare primary immunodeficiency disorder characterized by impaired immune responses to bacterial infections. It can present with similar symptoms to LAD, such as recurrent infections and impaired pus formation [7].
• Autosomal dominant hyper IgE syndrome: This is a genetic disorder that affects the immune system, leading to recurrent skin and lung infections. It can also be associated with impaired wound healing and leukocytosis, similar to LAD [13].
• Chronic granulomatous disease: This is a rare primary immunodeficiency disorder characterized by impaired killing of bacteria and fungi by neutrophils. It can present with similar symptoms to LAD, such as recurrent infections and impaired pus formation [13].
• Neutrophil dysfunction: This refers to a group of disorders that affect the function of neutrophils, leading to impaired immune responses to bacterial infections. It can be associated with similar symptoms to LAD, such as recurrent infections and impaired wound healing [13].

It's worth noting that these conditions are not necessarily obsolete, but rather they were mentioned in the context as potential differential diagnoses for leukocyte adhesion deficiency syndromes.

References:

• [7] Differential diagnoses include IRAK-4 deficiency, autosomal dominant hyper IgE syndrome, chronic granulomatous disease (see these terms), neutrophil dysfunction and a ...
• [13] Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency characterized by defects in the leukocyte adhesion process, marked leukocytosis and recurrent infections. ... Differential diagnoses include IRAK-4 deficiency, autosomal dominant hyper IgE syndrome, chronic granulomatous disease (see these terms), neutrophil dysfunction and a ...