Please note :-that links and passages in italics, are given as fact-based Reference.
Certain phrases are underlined and in red, to draw specific attention to the fact. I went totally blind myself due to Iga bullous disease , and many lessons were learned, hitherto unknown, throughout the progression of the disease, and therefore it is essential that patients and clinicians alike , take specific note of those phrases, in order to give the patient the best possible outcome.
It is totally wrong to assume that it is only certain types of bullous disease that affect the eyes. ANY bullous disease can affect the eyes, it is after all just mucous membrane, and given the fact that over 90% of patients with IgA mediated bullous disease , have mucosal involvement, and given that the IgA antibody is normally found in tears, it stands to reason, and common sense, that these patients are at high risk of having ocular involvement.
Bear in mind the added problem of the use of systemic steroids, (used to treat the inflammatory processes of bullous disease), also frequently cause sub-capsular cataracts, the removal of which again put the patient at risk of having blisters appear in the cornea, due to invasive surgery and contact, both of which are known, and have proven to excite the condition.Links to other blogs...
Autoimmune Diseases only occur in people who carry the genetic predisposition to an abnormal immune response ever occuring. The disease manifest, is simply the pathogenic result of the abnormal immune response. The "trigger" causing the mounting of an immune response, and stimulating these faulty genes, differs from person to person, even if the resulting disease is the same. For eg: An allergy to a drug may be the trigger resulting in the stimulation of these faulty genes, in one person, and possibly a hormone dysfunction in another, but both resulting in the same disease. Usually the cause is in fact multifactorial, however.
Some autoimmune diseases are hereditary, but neither Linear IgA disease ,nor IgA mediated Epidermolysis Bullosa Aquisita (a phenotype of EBA which mimics Liga) are not. The main typical form of EBA is IgG mediated and is hereditary. These Bullous Diseases are not contagious. They are known as heterogenous diseases, which means having a variety of characteristics, abilities, or appearances.
The underlying causes of these bullous diseases are the same as for any other autoimmune disease.
(see -Disorders of The Immune System- Autoimmunity)
Linear Immunoglobulin Antibody Bullous Dermatosis (LigA)
Linear Immunoglobulin Antibody (IgA) Bullous Dermatosis (LAD)This is a very rare, blistering , Autoimmune Disorder,which manifests as blistering of the skin and the mucous membranes. The childhood version is called Linear IgA Bullous Disease of Childhood (LABDC), and is immunologically identical to the adult disease.There is no difference clinically , or immunopathologically , between Linear IgA disease in adults, and LigA of childhood. (see Ref.Below)
From The British Association Of Dermatology Journal...Chronic bullous disease of childhood, childhood cicatricial pemphigoid, and linear IgA disease of adults. A comparative study demonstrating clinical and immunopathologic overlap.Wojnarowska F, Marsden RA, Bhogal B, Black MM.Department of Dermatology, Slade Hospital, Oxford, England.Linear IgA disease of adults, chronic bullous disease of childhood, and the rare childhood cicatricial pemphigoid currently are regarded as separate clinical entities despite their many shared features. All are sulfone-responsive subepidermal bullous diseases associated with linear IgA deposition at the basement membrane zone. In this paper we present a long-term study of 25 cases of adult linear IgA disease, 25 cases of chronic bullous disease of childhood, and four cases of childhood cicatricial pemphigoid, which has revealed further similarities among all three groups. The morphology and distribution of the cutaneous and mucosal lesions were similar; mucosal involvement was present in 80% of patients with adult linear IgA disease, 64% of those with chronic bullous disease of childhood, and 100% of those with childhood cicatricial pemphigoid, and ocular scarring affected patients in all groups.Remission occurred in 64% of those with chronic bullous disease of childhood (the disease was active in 12% after puberty), 48% of those with adult linear IgA disease, and in no cases of childhood cicatricial pemphigoid. HLA B8 and circulating IgA anti-basement membrane zone antibody were more common in chronic bullous disease of childhood than adult linear IgA disease. There were no absolute differences among the three groups, and we suggest that adult linear IgA disease, chronic bullous disease of childhood, and childhood cicatricial pemphigoid are the same disease, with childhood cicatricial pemphigoid being a more severe form of chronic bullous disease of childhood.
In LigA bullous disease, there is a defect or mutation in the genes, (as is the case in all autoimmune diseases) that promote the formation of ("express") a protein found in all human skin known as a Keratinocyte. This protein which is important in maintaining the integrity of the skin, is found in the lower layers of the epidermis. (Base Membrane Zone (BMZ) )As a result of these gene defects or mutations, the pathogenesis of other cells of the immune system, within this abnormal immune response, malfunction. B lymphocytes, (a type of white blood cell) malfunction, and produce this IgA antibody abnormally (now referred to as an IgA autoantibody). The IgA autoantibody produced because of malfunctioning cells, binds with this protein, and it results in acantholysis (the cells come apart, leading to fluid accumulation between layers of skin and forming blisters, inflammation and tissue damage,) being the manifestation of this disease. (See under Disorders of the Immune System-Autoimmunity)
Linear IgA disease onset in the majority of cases, usually occurs idiopathically. Idioipathic cases of autoimmunity usually occur spontaneously and for no known reason, and possibly by endogenous factors such as hormones or other gland/cell secretions. However, it sometimes follows infection and is rarely caused by drug allergy. (exogenous factors)
The word Idiopathic....Latin Greek idiopathia =(primary disease) = idiopatheia idio=(one's own) idios = (personal) patheia=(feeling) pathic =(suffering)
OR.....It can also be stimulated (only in an already genetically predisposed person), by an allergy to certain non-self exogenous enviromental factors such as.... certain drugs,( the most often cited being (vancumycin,) or a virus, these being the most likely of enviromental factors, concerning this disease. Drug-induced disease usually resolves with withdrawal of the offending agent or other enviromental factor, but it can take from months to years before the results of the autoimmune response stops. Given the rarity of the disease, common infections are unlikely to be the only factors if at all, involved in the pathogenesis of this disease.
Linear Iga disease, on first examination can be confused with Dermatitis herpetiformis,(DH) an IgA mediated autoimmune disease stimulated by an allergy to Gluten. Dermatitis Herpetiformis does not have circulating antibodies (whereas LigA does) and the blisters which are manifest in DH are usually much smaller, in a herpetiform (clustering) pattern.There is granulated deposition of Iga antibody in the dermal papillary tips of the BMZ, (Base membrane zone) in dh, and there are no circulating antibodies in blood serum. Blistering improves on omitting gluten from the diet, but it can take many months for the manifestation of the autoimmune response to disappear.
Patients with linear IgA dermatosis can present with lesions resembling epidermolysis bullosa aquisita, bullous pemphigoid, lichen planus, or cicatricial pemphigoid. One argument for this heterogeneity (mixed) of presentations is the possibility that multiple antigens may serve as targets for disease manifestation. Which means that it affects skin and mucous membranes, and therefore wherever in the body these tissues are present, then it can affect it. (see most common areas in list below) The location of these targets can yield clinical presentations that are associated with the aforementioned cutaneous diseases. A 97-kDa protein, which is identical to a portion of the extracellular domain of the 180-kD ,a bullous pemphigoid antigen (BPAG2, collagen XVII), has been determined to serve as the antigen commonly targeted in linear IgA dermatosis.
The lesions of Linear iga disease sometimes, in some cases, have a heterogeneous (mixed) presentation, comprising urticated plaques, papules, vesicles and blisters. Blisters can arise from normal skin and from urticated plaques, they may vary in size, and can appear in two distinct ways, either in a linear (line) presentation like a string of beads, or in a ring , forming the “crown of jewels” effect. Sometimes there are also inflamed pink/red papules, like small hard swellings.
Medical Terminology .....
cutaneous diseases (skin diseases)
heterogeneous (Having a variety of characteristics, abilities, or appearances.)
urticated plaques (itching, inflamed areas)
papules (small solid circumscribed bump in the skin )
vesicles and blisters (contain fluid).
Areas of the body that can be affected in Iga Bullous Disease
It is totally untrue that Liga does not affect the "inside" of the body, as I have seen reported. It most certainly can!! Wherever there is "skin", or type of skin, like mucous membranes. It usually affects "skin inside," that leads to an opening to the outside, simply because IgA is the dominant antibody guarding these passages.
It can affect the basement membranes in:- cornea, & conjunctiva & lacrimal glands (the eye) oral mucosa gums and pallate & salivary glands(mouth) oesophagus, (gullet) intestine, (gut) kidney collecting ducts ureter, bladder, & urethra, thymus. larynx & pharynx (throat basically) trachea (windpipe) & bronchial mucosa. (air passages to the lungs) nasal passages vagina, cervix, & rectum
Diagrams of Skin and Mucous Membrane
As in all epithelia, the basal surface of the cells rests on the basal lamina, a fibrous network of collagen and proteoglycans that supports the epithelial cell layer. The apical surface faces the intestinal lumen. Tight junctions, lying just under the microvilli, prevent diffusion of substances between the intestinal lumen and the blood via the extracellular space between cells.Gap junctions allow movement of small molecules and ions between the cytosol of adjacent cells. The remaining three types of junctions, adherens junctions, spot desmosomes, and hemidesmosomes are critical to cell-cell and cell-matrix adhesion.
NB: It is the loss of this adhesion due to these cells being targeted by the malfunctioning antibodies that causes the seperation of these cells and the subsequent filling with fluid causing blisters.
See fact based references below concerning areas affected in different patient cases
1) This study characterizes a novel basement membrane component that is the target of autoantibodies in patients with linear IgA bullous dermatosis. Tissue surveys showed that this protein localized to the epidermal side of 1 M NaCl split skin and to basement membranes in cornea, oral mucosa, esophagus, intestine, kidney collecting ducts, ureter, bladder, urethra, and thymus. http://www.ncbi.nlm.nih.gov/pubmed/8618013?dopt=Abstract
2) Two cases of linear IgA bullous dermatosis initially presenting as ulcerative lesions in the larynx and pharynx are reported. http://www.medscape.com/medline/abstract/15949090
3) A 54-year-old man is described, suffering from adult linear IgA bullous dermatosis with involvement of the bronchial mucosa. The main respiratory symptoms were recurring haemoptysis, episodic narrowing of the airways and persistent non-specific bronchial hyperreactivity. https://lirias.kuleuven.be/handle/123456789/15310
4) Two cases of adult linear IgA disease (LAD) with oral and colonic involvement are presented.Lesions in mucous membranes heal with scarring and therefore pose considerable morbidity, as scarring in this type of tissue continues to grow, and can cause serious problems in the throat or gullet, by closing off the airway or digestive tract, and if in the eyes, can result in blindness. Cutaneous (skin) lesions normally heal without scarring. http://cat.inist.fr/?aModele=afficheN&cpsidt=3656092
Linear Iga disease affects all types of skin including Mucous Membranes.Symptoms vary from mild to severe pruritis accompanied by a burning sensation, and blisters. These symptoms can affect any part of the body. Contact and friction from such articles as clothes, labels inside clothes, underwear, shoes, waistbands, surgical stockings, and spectacles can cause blistering. The use of surgical tape used in dressings is a particular problem. Surgery and medical procedures also excite blistering, for example, use of airway apparatus during anaesthesia, taking blood samples, injections, dental procedures and pap smears.
Mucous Membranes Cover all body cavities with exterior openings
Quote :-Proff. Neil Cox Consultant Dermatologist Carlisle Cumbria England (only in italics)People with iga mediated disease are more likely to get mucosal involvement, because the iga antibody, which is also found in tears and saliva, is the dominant antibody of these tissues.These tissues line the tracts of the body that come into contact with external, "out of the body" organisms.
Mucosal involvement is common, affecting 80% of adults and 64% of children. Hoarseness is an indication of pharyngeal or laryngeal involvement. Excess mucous, bleeding, an indication of nasal involvement. In these tissues, it causes ulcers, erosions, and blisters, involving the oral mucosa,(mouth), gums, which results in, Desquamative gingivitis (thereby damaging teeth), pharynx, larynx, trachea & Bronchi, salivary glands, nasal passages, rectum, vagina, oesophagus, intestine, kidney collecting ducts, ureter, bladder, urethra, thymus, eyes (cornea and conjunctiva), and lacrimal glands.
Potential Ocular (eye) involvement, including the lacrimal glands, is different and far more serious, and can lead to Blindness. It should not be assumed that only certain phenotypes of IgA mediated disease affect the eye. IGA Mediated disease affects mucous membranes, it therefore can affect the conjunctiva , and the cornea gets "caught up" with the inflammation of this affected tissue .
Quote: Mr. G. Ainsworth Consultant Ophthalmologist Csle.Cumbria England (in italics only.) Please note that All bullous (blistering ) diseases can affect the eyes. a) because it is mucous membrane, b) 80% of liga cases have mucosal involvement. c) The dominant antibody for these tissues is IgA
Some patients do not have mucosal involvement on presentation , but can develop it later, ranging from a few months to 2 or more years after initial diagnosis.Changes can occur, which may be actually present in the absence of ocular symptoms, such as fine scarring, or other defects due to involvement of the lacrimal glands and diminished tear production; both of which even independantly, can lead to blindness.
The progression of ocular Linear iga can prove to be very rapid and is indistinguishable from Cicatricial Pemphigoid when involving mucous membranes, and epitheliel tissue.
Symptoms develop of acute and chronic conjunctival inflammation, Symblepharon, blepharitis , entropion, trichiasis, tear deficiency, corneal ulceration, infection, and other ocular scarring complications resulting from severe mucosal disease.
Please note that ALL of these conditions listed below affect the eye in ALL types of Bullous disease of the eye .
1) lacrimal glands:- (The glands which produce tears). In order for the eye to remain healthy, it must remain moist. The lacrimal gland is a specialized gland located under the outer one-third of the upper eyelid that produces tears. Each time you blink, the eyelid spreads the tears over the surface of the eye and pumps excess tears into the tear ducts that drain the tears into the nose.
2) Dry Eyes:- If the lacrimal gland fails to produce enough tears to properly wet the eye, the surface of the eye begins to dry out. An eye that is too dry, may burn, sting, or feel like there is sand in it. Dry eye is most often treated with lubricating drops and ointments that help to control the drying and irritation. Sometimes plugs need to be placed in the drainage ducts to increase lubrication.
3) Symblepharon:- (Adhesions of one or both eyelids to the eyeball, either partial or complete)
4) blepharitis:- Anterior blepharitis - affects the outside front of the eyelid, where the eyelashes are attached. Posterior blepharitis - affects the inner eyelid (the moist part that makes contact with the eye)
5) conjunctiva :-The thin clear mucous membrane that covers the white portion of the eye (sclera) and lines the eyelids, providing protection to the eyeball.
6) the occlusion of punctae :- (To close, and block the tear drainage tubes of the medial canthus (near the nose) in order to keep artificial tears in the eye) This can be recurrent, having to be done again and again.
7) Trichiasis:- A condition in which the hair adjacent to a natural opening turns inward and causes irritation, as in the inward turning of the eyelashes upon the eye.
All of the above results in.....
8) entropion:- a medical condition in which the eyelids fold inward. It is very uncomfortable,and painful as the eyelashes rub against the cornea constantly, This in turn can damage the cornea causing ulceration , which can result in blindness. Dry eyes are the usual cause of entropion. If the lacrimal glands are also affected with a bullous disease, no tears or diminished tears result. Another of the causes of entropion is of bullous disease affecting the conjunctiva , which apart from covering the eye ball lines the inside of the eye lids. This in turn scars , pulling the lids under. In combination, the situation is acute. A surgical operation called an ectropion, turns the lid margins back to the original position. This is done by cutting the margins away from the lid , turning them back out to the original position , and stitching them into place.In conjunction with all of the above......Epithelial swelling damages vision by changing the cornea's normal curvature, and causing a sight-impairing haze to appear in the tissue. Epithelial swelling and inflammation, will also produce tiny blisters on the corneal surface. When these blisters burst, it results in exposing the nerves that line the cornea, causing very severe pain. Even the involuntary act of blinking can be painful.
Disease or infection, which can be caused inadvertantly or without due care by a physician or other health carer. eg. cross infection due to lack of proper care in washing hands, or wearing of protective clothing.
From my own experience, having lost both my eyes and lacrimal glands to IgA mediated Bullous disease , it was discovered that Topical treatments to the eyes, either eye drops or ointments worked better and had a longer effect if applied in minimum strengths but more often. Many times, the normal dose or strength proved to actually cause a blister on the cornea. The ONLY really successful treatment (in my case) that had an immediate good result , ridding the corneas of blisters, was IV Methyl Prednisolone. I also became allergic to many of the topical treatments to my eyes, through regular use. Chloremphenocol drops Cefuroxane, Gentamycin, to name but a few. Even Atropin started to cause a reaction in time.