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MANIFESTIONS OF PRIMARY
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Non-specific cutaneous manifestations These are caused by different factors mainly the following:- Infections and ulceration: Recurrent furuncles or abscesses. Bullous impetigo with clear blisters. Cutaneous ulcers due to secondary infection by viral diseases such as herpes simplex virus or varicella-zoster viruses due to T-lymphocyte defects . Viral warts. Vesicobullous lesions: A vesicular presentation of the hyper-IgE syndrome in infancy has been described . Candidiasis . Refractory cutaneous and mucosal candida infections may present with signs of severe immunodeficiency disorders, particularly severe combined immunodeficiency due to T-lymphocyte defects. Morbilliform eruptions. These are early feature of severe combined immunodeficiency disease and of DiGeorge‘s syndrome . Petechiae. Petechiae, due to thrombocytopenia, are a highly characteristic feature of the Wiskott-Aldrich syndrome, and may also occur in Fanconi‘s anemia , dyskeratosis congenita and the Chediak-Higashi syndrome. Erythroderma. A combination of erythroderma of early onset with failure to thrive is highly suggestive of immunodeficiency .It is a rather non-specific feature of immunodeficiency in infancy. Eczema. Eczema is a characteristic feature of certain well-established immunodeficiency disorders such as the Wiskott-Aldrich syndrome, Agammaglobulinemia, selective IgA deficiency , selective IgM deficiency, and ataxia telangiectasia . Lupus erythematosus. There is an increased incidence of systemic lupus erythematosus in patients with IgA deficiency, and skin lesions closely resembling discoid lupus erythematosus .
SYNDROMES ASSOCIATED
Fatal varicella . Chronic Candida granuloma . Atopic eczema and asthma . Recurrent bacterial infections of the respiratory tract . Autoimmune disorders may complicate IgA deficiency mainly SLE, rheumatoid arthritis, dermatomyositis, pernicious anemia, vitiligo and idiopathic thrombocytopenic purpura. Anaphylactic reactions following transfusion of blood or administration of immunoglobulin, due to the presence of IgE and anti-IgA antibodies.
Eczema. Large Viral Warts. Meningococcal and pneumococcal infections.
Hyper-IgM syndrome is an autosomal X- linked affects predominantly boys . General Features Recurrent bacterial infections, particularly tonsillitis, otitis media and pneumonia, usually starting during the first or second year of life. Skin manifestations : extensive viral warts . Mucous membranes manifestations : stomatitis, gingivitis and oral ulceration occurring secondary to neutropenia. Blood picture : IgM is elevated while IgG , IgA and IgE are reduced. Neutropenia .
This syndrome reflects an abnormal development of the third and fourth branchial (pharyngeal) pouches. Clinical Manifestations Skin manifestations: affected children have skin lesions simulating “seborrhoeic dermatitis“, atopic dermatitis, and ‘maculopapular rashes‘ . Persistent oral candidiasis is a common presenting feature, in those infants who survive the neonatal period. General manifestations Absence of the parathyroid glands . Defects of the heart and great vessels. Defects of the head and neck, and thymus hypoplasia leading to a congenital T-cell defect.
This term is applied to a syndrome comprising several genetically distinct disorders with similar clinical and immunological features. This syndrome is characterized by metabolic defects with deficiency in adenosine deaminase, purine nucleoside phosphorylase enzymes, deficiency of DNA-binding protein and a defect in the production of interleukin-2. Death is common in the first few months of life . Clinical features These patients have marked deficiencies both of T- and B-lymphocyte function. Mucocutaneous manifestations Mucocutaneous and systemic candidiasis is the most common manifestations. Dermatophyte infections may occur and may present as a chronic and refractory napkin dermatitis. ‘Ichthyosiform erythroderma‘ with ‘alopecia and absence of eyelashes and eyebrows‘ or ‘ectodermal dysplasia‘. Toxic epidermal necrolysis like lesions . Viral infections manifesting with skin ulcerations particularly in the perineal area, the oral mucosa or the tongue . Severe varicella-zoster infections may also occur. General manifestations Recurrent infections mainly pneumonia , viral infections due to Cytomegalovirus , measles or pneumocystis Carini . Chronic diarrhea (due most commonly to rotavirus, Campylobacter, or to parasites such as Giardia or Cryptosporidia . Treatment A bone-marrow graft is the only effective treatment.
This syndrome is transmitted as an autosomal recessive trait, characterized by defect in expression of histocompatibility antigens on B- and T-lymphocytes and on monocytes, either of class I or class II . Class I antigens are particularly important for viral cytotoxicity and both class I and class II antigens are required for antigen presentation to T-lymphocytes. Death in early childhood is common . Clinical Manifestation Increased susceptibility to candida infections. Lung infections caused by different organisms mainly pneumocystis carini. Severe diarrhea . Septicaemia and marked vulnerability to viral infections, including herpes virus hominis, Coxsackievirus and poliomyelitis.
This is an autosomal recessive inherited familial syndrome , where most of the manifestations are cutaneous . It appears that the disorder reflects proliferation of T-lymphocytes at the expense of the B-lymphocyte. The disease has a rapidly fatal course, with failure to thrive and recurrent infection . Skin manifestations Erythematous scaly rash and confluent erythroderma . General manifestations Hepatospleenomegaly and generalized lymphadenopathy . Chronic diarrhea. Lymphoma may develop in some cases. Eosinophilia and lymphocytosis. Loss of B-cells and falling levels of all immunoglobulin other than IgE, which may be elevated. Treatment Bone marrow transplantat offers the only real therapeutic hope for these infants .
This is a genetically determined disorder characterized by: Thrombocytopenic purpura. Eczema and recurrent infections. Death in childhood is common. The gene for the Wiskott-Aldrich syndrome has been mapped to Xp11. Lymphocytes, neutrophils and platelets from patients with Wiskott-Aldrich syndrome have been shown to have altered expression of a heavily glycosylated surface protein called sialophorin (CD43 ) . Blood Picture Thrombocytopenia. Platelets are small and fail to aggregate with reduced platelet production and number . Immunoglobulins: Hypercatabolism of immunoglobulins. Raised IgE and decreased IgG . Absent isohaemoagglutinins . IgG2 subclass, is frequently impaired . Antibody responses to protein antigens are less severely impaired. Lymphocytes are small and show characteristic morphological abnormalities. Treatment Fresh platelets transfusion for acute bleeding. Spleenectomy reduces the danger of bleeding, increases the platelet count and improves platelet function. Spleenectomy increases the risk of fatal septicaemia, but this risk can be minimized by long-term prophylactic administration of antibiotics, particularly Cotrimoxazole . Gammaglobulin: intravenous immunoglobulin administration has a definite place in the control of infection, where antibiotic therapy alone is inadequate. Gamma globulins by the intramuscular route are contra-indicated because of the risk of hemorrhage at the injection site . Bone marrow transplantation. Genetic counseling of parents and possible female carriers in the family is important.
Ataxia telangiectasia is an autosomal recessive disorder characterized by: Skin manifestations An extensive scaly erythematous rash may be an early feature in infants who do not die immediately, progressing to erythroderma, and associated with alopecia . Atrophy with mottled hypo- and hyperpigmentation, café au lait macules, often in a dermatomal distribution, photosensitivity, premature graying of the hair, acanthosis nigricans and eczema are common manifestations. General Manifestations Mucous membrane manifestations. Mucocutaneous telangiectasia . Progressive ataxia . Recurrent sinus and lung infections. Combined immunodeficiency . Increased liability to malignancy . Recurrent episodes of acute metabolic illness. Striking neurological problems including fits. Lactic acidosis occurs within the first few days of life. Death may occur rapidly unless the diagnosis is made and treatment is started early. Bacterial and viral infections cause high mortality. Diagnosis Diagnosis is confirmed by identification of a characteristic pattern of organic aciduria. Prenatal diagnosis can be carried out in a number of ways and affected fetuses can be treated by maternal biotin. Blood picture The peripheral blood count generally reveals eosinophilia and lymphopenia. IgA deficiency and T-cell defects are very common. Treatment Treatment is with biotin 10-40 mg daily.
Biotin-dependent carboxylases appear to be important for normal immune function. Clinical Manifestations A scaly erythematous rash appears in the interdigital webs , in the flexures of the groins and axilla. Periorificial eczematous eruption that is often confused with the rash of zinc deficiency. Alopecia is of the diffuse type and there may be alopecia totalis. Candida is often isolated from the rash. Immunodeficiency has been reported, particularly absent delayed hypersensitivity skin tests to Candida, and absent in vitro T-lymphocyte responses to Candida antigen. Diagnosis The findings of low serum and urine biotin levels, and a low serum biotinidase level confirm the diagnosis. Treatment Treatment with biotin 5-10 mg daily is very effective, though loss of vision and hearing due to long-standing untreated disease may not recover.
This is a rare disorder, probably transmitted as an autosomal recessive trait, in which combined immunodeficiency is associated with partial albinism and an absence of cutaneous langerhans cells . Hair of eyebrows and eyelashes are silvery-gray from early childhood.
This syndrome may be congenital or acquired . Congenital neutropenia. Persistent chronic neutropenia of childhood results in high mortality rate. This is genetically transmitted both as an autosomal recessive and autosomal dominant . Acquired neutropenia. This may be due to drugs , bone marrow hypoplasia and transient in the course of febrile illnesses . General Features Presentation is usually within the first few months of life. Neutrophils appear to be responsible principally for the protection of those surfaces of the body that are in direct contact with the external environment. Recurrent skin infections When the neutrophil count is less than 500/mm3, patients are at considerable risk of infection. Cutaneous abscesses, furunculosis and cellulitis are the most frequent types of infection. Otitis media , stomatitis and gingivitis are common. These are usually caused by staphylococcus aureus and less common by Gram-negative organisms such as Escherichia coli and pseudomonas species. Systemic infections Other common infections include lung abscesses , pneumonia, meningitis and septicaemia are dangerous complications. Fungal infections are a particular problem, especially infections caused by Aspergillus and Candida species. Periorificial eczematous eruption : This is often confused with the rash of zinc deficiency. Treatment Bone marrow transplant. Cyclical Neutropenia This is an autosomal dominant disorder in which the circulating neutrophils disappear at regular intervals of about 21 days. Clinical Manifestations The manifestations first appear in childhood presenting with : Recurrent pyrexia Oral ulceration Cervical lymphadenopathy . Cutaneous furunculosis. Treatment The condition tends to improve spontaneously after a few years. Treatment with human granulocytes and colony-stimulating factor appears promising. Neutropenia and associated syndromes Neutropenia also occurs as a part of certain syndromes : Pancytopenia as in Fanconi‘s anemia. Dyskeratosis congenita. Chediak-Higashi syndrome. Griscelli‘s syndrome. Secondary event in the primary immunoglobulin deficiencies .
The syndrome is transmitted as an autosomal recessive trait. Children with Fanconi‘s anemia are generally small, and have a history of low birth weight. Death is usually within a few years of the first signs of bone marrow failure. Clinical Manifestations Skin manifestations Easy bruising is generally the early presenting symptom, and most often appear between the ages of 4-10 years. Cutaneous hyperpigmentation and skeletal anomalies are characteristic. Macular brownish pigmentation, either resembling freckles and occurring mainly on the sun-exposed areas. The abdomen, genital area and flexures appear to be predominantly affected . Guttate macular hypopigmentation is often present in affected areas. General manifestations Progressive bone marrow failure during childhood and adolescence. Thrombocytopenia, anemia and leucopenia are usual, and the bone marrow is aplastic. The principal skeletal abnormality is the absence or hypoplasia of at least one of the thumbs. Hypoplasia or absence of the radius is also common. Structural renal abnormalities are also frequently present. Intelligence is usually unimpaired. There is a high incidence of leukemia and other malignancies in these children. There is a high incidence of diabetes and of neoplastic disease . Treatment Bone marrow function can be stimulated with corticosteroids and with the androgenic steroid, oxymethalone. Bone marrow transplant has been used successfully to treat patients, but care must be taken to avoid the use of alkylating agents in pretransplanted cases.
This is an X-linked form of progressive marrow failure, which has in the past been greatly confused with Fanconi‘s anemia. The non-hematological features are however entirely distinctive.
The hyper-IgE syndrome is a primary immuno-deficiency state transmitted by an autosomal dominant gene. This is characterized by recurrent staphylococcal infections and markedly raised serum IgE levels. Clinical Manifestations Skin manifestations Affected children have skin rash that may appear as early as the first few days of life, which may be vesicular. An eczematous rash appears, which is excoriated, papular and pustular, more frequent on the scalp. The scalp margins and the proximal flexures such as the axillae, groins and neck are also common sites . Bacterial skin infections such as furunculosis. Skin abscesses tend to favor the scalp, face and neck. General manifestations Candida Infections of the ears, sinuses, joints and viscera are also common. Oral candidiasis and candida nail infections. Pneumatocoeles may lead to aspergillomata. Recurrent lung infections by staphylococcus aureus. Infection is also seen with haemophilus influenza, pneumococci, group A streptococci that may lead to the development of pneumatocoeles , lung abscesses and empyemas. Growth failure may be prominent in affected children, and some patients have had unexplained osteoporosis, predisposing to frequent fractures . Pathology Peripheral blood eosinophilia may be marked, up to 50-60% . Serum IgE levels are consistently very high even in infancy. Elevated IgD levels. IgG, IgA and IgM levels are usually unremarkable. Great increase in circulating total IgE. Patients show strongly positive immediate wheal and flare responses on skin prick testing with foods and commonly inhaled allergens, as well as bacteria and fungal antigens . Peripheral blood lymphocytes are generally normal, and no abnormality of T-cells. Treatment Antibiotic prophylaxis. Cimetidine is often given to those who respond poorly to antibiotics alone. Candida infections should be treated topically with oral ketocazole or the new antifungal preparation such as itraconazole. Persistent pneumatocoeles should be excised .
This disorder is inherited as an autosomal recessive trait, which is characterized by leukocyte dysfunction. This leads to absence of pus in tissue lesions clinically and histologically. Abnormalities of lymphocyte function are also present, particularly diminished natural killer-cell (NK) and T-cell cytotoxic functions. Clinical Manifestations Recurrent cellulitis, abscesses and ulceration of the skin and soft tissues are the main manifestations. The organisms usually isolated from these abscesses are either staphylococcus aureus, or Gram-negative bacteria such as Escherichia coli or pseudomonas. Recurrent otitis media and poor wound healing may be an important presenting feature. Superficial Candida infections are common. Ulcerative stomatitis and severe periodontal disease, leading to premature loss of teeth are very frequent problems. Peritonitis is common and frequently causes serious complications. Delayed separation of the umbilical cord and omphalitis. Diagnosis Definitive laboratory diagnosis depends upon the demonstration of deficient surface expression of CD11a, CD11b and CD11c on polymorphs, lymphocytes and monocytes. Prenatal diagnosis is available requiring fetal blood sampling. Treatment Antibiotics . Neutrophil infusions. Bone marrow grafting .
Chronic granulomatous disease is an inherited disorder of phagocyte bactericidal function, characterized by the development of granulomatous lesions in many tissues. Short stature is a prominent clinical feature in children and adults with chronic granulomatous disease. Survival rate is variable but improvement occurs in about 50% of patients. The onset of symptoms after infancy predicts a better prognosis. Pathology In chronic granulomatous disease, phagocytes are able to ingest bacteria normally, but cannot subsequently kill them. The same abnormality is also present in eosinophils and mononuclear phagocytes. The intracellular survival of the ingested bacteria leads to the development of granulomata in lymph nodes, skin, lungs, liver, gastrointestinal tract or bone. Clinical Features Neonatal pustulosis is commonly the first sign of the disease. Empetiginized periorificial rash around the nostrils, ears, mouth and eyes, perianal abscesses are highly characteristic features. Nodular lesions and necrotic ulcers. Subcutaneous nodules may develop at immunization sites, and these also tend in time to ulcerate. Poor healing of surgical wounds, discharging nodular skin lesions, are highly characteristic and are a regular features. Enlargement of the superficial and suppuration of lymph nodes. Other frequent findings include: Chronic suppurative paronychia. Folliculitis of the scalp . Ulcerative stomatitis. Infections occur in other organs particularly the lungs, the visceral lymph nodes, liver and bones. Pulmonary disease is prominent, with recurrent pneumonia, empyemas and lung abscess formation . Gastrointestinal manifestations include: malabsorption, perianal abscesses, fistulae and oral ulceration. The characteristic manifestations are obstructive lesions associated with granulomatous infiltration . Blood Picture Peripheral blood leucocytosis is characteristic, reflecting increased numbers of circulating neutrophils. Microcytic hypochromic anemia . Levels of the three major classes of immunoglobulin are increased, with increased or normal IgE. Treatment Skin hygiene. Pyrexia should be investigated carefully to reveal the site of infection and the responsible microorganism . Antibiotics should be chosen carefully and therapy should be vigorous. Continuous antibiotic treatment, with trimethoprim-sulphamethoxazole (Bactrim, Septrin) or with Trimethoprim alone, is now a standard line of treatment Continuous antifungal therapy with ketoconazole does not appear to be effective in preventing Aspergillus but it is hoped that itraconazole, currently under evaluation, will prove to be superior. Subcutaneous interferon-gamma, globulins may have a good response. Blood transfusions may be required to treat anemia. Systemic corticosteroids for intestinal obstruction . Bone marrow transplant.
This syndrome may be transmitted as an autosomal recessive trait. It is characterised by: Combination of malabsorption and failure to thrive. Neutropenia due to pancreatic exocrine insufficiency . Metaphyseal chondrodysplasia, which tends to result in deformities, particularly affecting the femoral heads. Clinical Features Cutaneous Manifestations A symmetrical ‘eczematous‘ rash has been reported in some patients and the occasional association of thrombocytopenic purpura and eczema may suggest the Wiskott-Aldrich syndrome. Cutaneous abscesses may be extensive. General manifestations Neutropenia is an important component of the disorder, though it may not become apparent during the first few years of life. Thrombocytopenia may also occur, and may result in petechiae or bleeding. Recurrent respiratory tract infections are occasionally serious . Hematological malignancies are common. Treatment Pancreatic extracts are effective. Treatment of skin and systemic infections .
Neutrophils contain several types of granules. Azurophil granules contain myeloperoxidase, a wide variety of degradative enzymes and cationic proteins which have potent antibacterial and antifungal properties. Neutrophil specific granules are more numerous than azurophil granules. Lysozymes are also present in azurophil granules, lactoferrin and vitamin B-binding proteins. Affected individuals have increased susceptibility to infections, particularly cutaneous abscesses and recurrent pneumonia, leading to progressive lung damage.
Myeloperoxidase deficiency is relatively common, and is inherited as an autosomal recessive trait. Myeloperoxidase is a component of neutrophil azurophil granules. The generation of oxyhalide radicals and other toxic intermediaries are important to the cell‘s microbicidal activity. The myeloperoxidase gene has been localized to chromosome 17 . Clinical Features Defective neutrophil bacterial and fungal killing in vitro. Incidence of bacterial infections is not increased. Deep candida infections . Complement deficiencies Deficiency of C2 is the most frequent. These are generally transmitted by autosomal recessive genes with the exception of C1 esterase inhibitor deficiency. Clinical Manifestations
Deficiency of the early components of the classical complement activation pathway leads to different clinical manifestations depending on the type of deficient complement. Manifestations of deficiency of different complements:
Clinical manifestations are. Systemic lupus erythematosus or a SLE-like syndrome. Manifestations as Henoch-Schonlein purpura or Sjogren‘s syndrome. Infections. This appears to be the most common complement deficiency. It has now been shown to be associated with a variety of diseases but deficient individuals are often entirely healthy. Clinical Manifestations The manifestations may simulate different diseases such as: Collagen diseases as systemic lupus erythematosus, discoid lupus erythematosus, membranous glomerulonephritis, rheumatoid arthritis and dermatomyositis. Henoch-Schonlein purpura. Crohn‘s disease. Idiopathic thrombocytopenic purpura. Bacterial infections may also occur, particularly pneumococcal, Haemophilus influenza and Meningococcal infections.
Infections are the main hazard of C3 deficiency. Meningococcal meningitis and pneumococcal pneumonia are the major problems. Clinical Picture Similar to that of hypogammaglobulinaemia. Transient maculopapular rashes have been reported to occur in association with infections. Other manifestations such as systemic lupus erythematosus and membranous glomerulonephritis.
Recurrent meningococcal meningitis. Disseminated gonococcal infections. Cutaneous infections and subcutaneous abscesses in few cases. Collagen diseases as systemic lupus erythematosus, discoid lupus erythematosus, Sjo“gren‘s syndrome, rheumatoid arthritis, sclerodactaly, Raynaud‘s phenomenon and ankylosing spondylitis.
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