• Introduction
• How is bullous pemphigoid diagnosed?
• What are the symptoms of bullous pemphigoid?
• Can bullous pemphigoid be cured?
• How is bullous pemphigoid treated?
• Where can I find out more information about bullous pemphigoid?

INTRODUCTION

Bullous pemphigoid (BUL-us PEM-fih-goid) is a rare skin condition that causes large fluid-filled blisters. They often appear on the skin near creases, such as the upper thighs and armpits. Sometimes, people get a rash instead of blisters. The affected areas may be painful and are usually very itchy. Blisters or sores also might form in the mouth, but this is rare.

Bullous pemphigoid occurs when the immune system attacks a layer of tissue in the skin. The reason for this immune system response is not well understood. In some people, the condition is brought on by certain medicines.

How is bullous pemphigoid diagnosed

The look of the rash, especially if blisters have formed, may be enough for your GP to make the diagnosis, but further investigations are usually performed including a blood test and skin biopsies (under local anaesthetic). This will determine which type of PEM (if any) is present. If BP is suspected, a skin biopsy is performed for histology and direct immunofluorescence testing. Samples from within and around the lesion are often used for histology, but samples of uninvolved skin (often about 3 mm from the edge of a lesion) are used for direct immunofluorescence. Biopsies reveal the layers of skin that are affected by the blisters and direct immunofluorescence shows where the pemphigoid antibodies are binding in the skin. A blood test usually shows the circulating autoantibodies specific to BP.

What are the symptoms of bullous pemphigoid?

The symptoms of bullous pemphigoid may include:

1. Itching, which can start weeks or months before blisters form.
2. Large blisters that don't break easily, often found along skin folds. On brown and Black skin the blisters may be dark pink, brown or black. On white skin they may be yellow, pink or red.
3. Pain.
4. A rash.
5. Small blisters or sores in the mouth or other mucous membranes. This is a symptom of a rare type of the disease called mucous membrane pemphigoid.

Bullous Pemphigoid blisters

Blisters are firm and filled with a fluid. Most commonly, the fluid is clear but, in some people, it can be bloodstained. The blisters will gradually grow as they fill with fluid and then burst, often leaving raw skin which is very sore. When the skin blisters heal, they do not leave permanent scarring but skin colour changes might be observed after the inflammation has settled down.

Can bullous pemphigoid be cured?

BP cannot be cured but with the correct diagnosis, management and treatment it can be controlled. However, sometimes it does slowly resolve itself after one to five years.

More information about bullous pemphigoid?

For more detailed information on BP, see the British Association of Dermatologists Patient Leaflet. The New Zealand Dermatology service, DermNet NZ, also produces very good literature on BP.

The UK Centre of Evidence Based Dermatology investigates aspects of BP. You can find videos and information about their findings on their website.

• Introduction
• How is pemphigus vulgaris diagnosed?
• How long will my pemphigus vulgaris last?
• How is pemphigus vulgaris treated?
• What drugs might I be offered to reduce the impact of pemphigus vulgaris?
• Where can I find out more information?

What is pemphigus vulgaris?

Pemphigus vulgaris is a rare autoimmune disease that is characterised by painful blisters and erosions on the skin and mucous membranes, most commonly inside the mouth. Pemphigus vulgaris accounts for 70% of all pemphigus cases worldwide although it is extremely rare in New Zealand (about one case per million of the population).

How is pemphigus vulgaris diagnosed?

Often it will be your GP or dentist who will make the initial visual diagnosis and offer a referral to a specialist depending on the part of the body affected. The most common departments are Dermatology, Ear, Nose and Throat (ENT), Maxillo-Facial (Max-Fax) or to a dental hospital.

A biopsy of a blister is usually taken to confirm the diagnosis. The biopsy sample will be processed in the laboratory and examined under a microscope. Part of the biopsy sample will be examined using a technique known as direct immunofluorescence to demonstrate the presence of PV autoantibodies in the skin. It is not unusual to have more than one biopsy taken, especially if both the skin and mucous membranes are involved.

Pemphigus vulgaris autoantibodies measured in the blood (by a specialist technique known as ELISA) can be a useful test to monitor how active the disease is and can help determine if a change of treatment is appropriate.

How long will my pemphigus vulgaris last?

PV is a chronic autoimmune disease with no known cure. Suppressing your immune system is necessary to keep the disease under control and make remission possible. The initial goal of treatment is to clear existing blisters and help prevent relapses. Treatment typically depends on the severity and stage of your disease, with early diagnosis and treatment beneficial to getting your condition under control. Unfortunately, this disease can have unpredictable episodes where it flares for a variety of reasons such as stress or illness in which case treatment may need to be adjusted.

How long does PV last?

Before the advent of corticosteroids, PV had a high fatality rate, with approximately 70+% of patients dying within a year. Nowadays, it is very rarely a cause of death. With treatment, lesions can heal normally without scarring and the hyperpigmentation associated with pemphigus usually resolves after several months-years. Most patients treated for PV will enter a partial remission within 2 to 5 years.

How does Pemphigus Vulgaris treated?

What is the treatment of pemphigus vulgaris?

The primary aim of treatment of pemphigus vulgaris is to decrease blister formation, prevent infections and promote healing of blisters and erosions [4,5]. Systemic corticosteroids are the mainstay of medical treatment for controlling the disease, usually in the form of moderate to high doses of oral prednisone or prednisolone, or as pulsed intravenous methylprednisolone. Since their use, many deaths from pemphigus vulgaris have been prevented (the mortality rate dropped from 99% to 5–15%). Corticosteroids are not a cure for the disease but improve the patient's quality of life by reducing disease activity. The doses of corticosteroids needed to control pemphigus vulgaris and the length of time on treatment may result in serious side effects and risks.

What drugs might I be offered to reduce the impact of pemphigus vulgaris?

Other immunosuppressive drugs (mostly off-label) used to reduce the dose of steroids and may be required by patients with pemphigus vulgaris for years. These are most often:

• Azathioprine
• Mycophenolate mofetil
• Cyclophosphamide

Rituximab, which is now approved by the Food and Drug Administration (FDA) in the US.

Other medications that are sometimes used in pemphigus (often in combination) include:

• Dapsone
• Methotrexate
• Tetracyclines
• Nicotinamide
• Plasmapheresis
• Intravenous immunoglobulin
• Extracorporeal photopheresis
• Immunoadsorption
• The TNFα inhibitor
• infliximab.

At optimal therapy, patients may continue to experience mild disease activity.

Other considerations include vaccination (live vaccines are contraindicated), bone prophylaxis, baseline ophthalmological assessment, and psychological support if needed.

Topical therapy

Topical therapy for cutaneous pemphigus vulgaris may include topical steroids and emollients.Treatment of mucosal pemphigus vulgaris may include various formulations of a topical steroid, intralesional steroid, topical tacrolimus, or topical ciclosporin.

General management

Appropriate wound care is particularly important, as this should promote healing of blisters and erosions.

• Handle skin very gently to avoid causing new blisters and erosions.
• Wear surgical gloves and use aseptic technique when changing dressings.
• Analgesics may be needed especially for dressing changes.
• Gently cleanse with an antiseptic solutionor take a bleach bath.
• Drain intact blisters, but leave the blister roof in place.
• Apply a bland emollient ointment, such as 50% white soft paraffin + 50% liquid paraffin, directly to the skin, or apply the ointment to a dressing.
• Use non-adherent dressings (such as petrolatum-soaked gauze or silicone mesh). These may incorporate an antiseptic.
• An absorbent dressing may be applied over the primary dressing if the erosions are oozing.
• Be vigilant in identifying and treating any infection.
• Patients should minimise activities that may traumatise the skin and mucous membranes during active phases of the disease. These include activities such as contact sports and eating or drinking food that may irritate or damage the inside of the mouth (spicy, acidic, hard and crunchy foods).

Oral hygiene and proper dental care are essential.

• Use a soft toothbrush and mint-free toothpaste to gently and thoroughly brush teeth twice daily.
• Rinse using an antiseptic or anti-inflammatory mouthwash.
• Treat oral candidiasis, if present.

Future prospects for treatment

There is future hope that future treatment for pemphigus will be more specific with fewer side effects. The CD20 antagonist ofatumumab has been reported to be effective. Investigators have engineered specific chimeric auto-antibody receptor T-cells to eliminate desmoglein-3-specific B cells in mice. The use of anti-neonatal Fc receptor is under investigation in combination with rituximab.

What are the complications of pemphigus vulgaris?

Pemphigus vulgaris can cause very extensive, life-threatening erosions, especially if the diagnosis is delayed. Other potentially severe complications may include:

• Secondary bacterial infection
• Fungal infection, especially candida
• Viral infection, especially herpes simplex
• Nutritional deficiencies due to difficulty eating
• Complications of systemic steroids especially infections and osteoporosis
• Complications of immune suppressive treatments
• The psychological effects of severe skin disease and its treatment (anxiety and depression)
• An elevated risk of cardiovascular disease (atherosclerosis heart failure, arrhythmia, thromboembolism, and cardiovascular death).

How is the severity of pemphigus vulgaris assessed?

The severity of pemphigus can be scored using various scoring systems.

• PDAI: Pemphigus Disease Area Index
• PAAS: Pemphigus Area and Activity Score
• PAS: Pemphigus Activity Score
• ABSDIS: Autoimmune Bullous Skin Disorder Intensity Score
• Saraswat oral pemphigus scoring
• Pemphigus vulgaris lesion severity score
• Harman pemphigus grading
• Kumar scoring system
• Mahajan scoring system

Where can I find out more information?

We recommend the British Association of Dermatologists Patient Leaflet, the New Zealand DermNetNZ website and the International Pemphigus and Pemphigus Foundation.

• Introduction
• How is pemphigus foliaceous diagnosed
• What are the symptoms of pemphigus foliaceous?
• What caused my pemphigus foliaceous?
• How long will my pemphigus foliaceous last?
• How is pemphigus foliaceous treated?
• Where can I find out more information about pemphigus foliaceous?

Introduction

Pemphigus foliaceus is a rare autoimmune condition that causes painful and itchy blisters and sores to form on your skin. The most common places for blisters and sores to form on your body are on your scalp, face, neck and back.

The main observable difference between PF and pemphigus vulgaris (PV), which is the more frequently diagnosed form of pemphigus, is the potential involvement of mucous membranes (mouth, nose, eyes, genitals, etc) frequently seen in PV. In PF, the skin is the only site to be affected. The blisters are the result of the "glue" in the upper parts of your layers of skin, being "attacked" by circulating antibodies (autoantibodies). This "glue" is a protein called a desmosone. In the case of PF, the particular desmosone affected is called a desmoglein-1. In PV, another desmosone is also affected (desmoglein-3). When the layers of the skin separate as a result, a blister forms and fills with fluid. In PF, the layer of the epidermis that is affected is close to the surface, so these blisters tend to be flaccid and burst easily, leaving erosions or crusts.

How is pemphigus foliaceous diagnosed

Skin biopsies are usually required to confirm the diagnosis. Two biopsies will be needed – one biopsy involving the edge of a blister for routine histology in formalin and a second perilesional (normal skin) biopsy which looks for evidence of the abnormal proteins in the skin.

Blood tests may allow identification of the abnormal proteins in the blood.

What are the symptoms of pemphigus foliaceous?

PF causes painful blisters to form on your skin. The blisters, or crusts, are fragile and break open easily, creating sore erosions. After the blisters burst, they leave a scaly, crusty area. These can be very itchy and painful. PF often appears as a painful rash on the face and upper body but can affect all of the skin. Over weeks to months, the blistering can progress, and more and more new lesions appear over the body, limbs, face, and scalp. Severe cases of PF can result in lesions all over the entire body, developing into something called an 'exfoliative erythroderma'. PF does not affect the mucous membranes (mouth, nose, eyes, genitals, etc). There are currently 6 known variations of pemphigus foliaceus:

• Pemphigus erythematosus
• Pemphigus herpetiformis
• Endemic pemphigus foliaceus
• IgA pemphigus foliaceus
• Paraneoplastic pemphigus foliaceus
• Drug-induced pemphigus foliaceus

What caused my pemphigus foliaceous?

Pemphigus foliaceus occurs when cells of the body's immune system produce proteins (autoantibodies) that damage the adhesion points between skin cells. These adhesion points act like press studs holding one of the top layers of the skin cells (epidermis) together. If they are damaged, the skin cells break apart and the top layer peels off. As the top layer is very thin, the blisters may not be noticed, and the skin may appear to be peeling only.

The cause of the immune attack on the skin is not known. Genetic and environmental factors are thought to play a role: some medications containing sulfur groups are thought to be involved; in countries where the condition is endemic in young people, certain parasitic infections and insects are thought to be involved.

Triggers which may initiate pemphigus foliaceus include sunburn, drugs containing thiol, vaccines and radiotherapy.

What other problems can occur with pemphigus foliaceus?

People with pemphigus foliaceus, together with members of their family, have an increased risk of other autoimmune diseases. The most common of these is autoimmune thyroid disease.

How long will my pemphigus foliaceous last?

These diseases are chronic and long term. There is no cure but remission is possible. The disease can be managed and "normal" life resumed.

Treatment of pemphigus foliaceous

Treatment for pemphigus foliaceous usually starts with medicines to ease symptoms and prevent new blisters. These may include steroids and medicines that target the immune system. If your symptoms were caused by use of certain medicines, stopping that medicine may be enough to clear up your symptoms.

Some people may need a hospital stay to receive fluids, nutrition or other treatments.

Medicines

Your healthcare professional may suggest one or more of the following medicines. The choice of medicines depends on the type of pemphigus you have, how severe your symptoms are and whether you have other medical conditions.

Corticosteroids. For people with mild disease, corticosteroid cream or injections may be enough to control it. For others, the main treatment is a corticosteroid medicine taken by mouth, such as prednisone pills.

Using corticosteroids for a long time or in high doses may cause severe side effects. These include diabetes, bone loss, an increased risk of infection, stomach ulcers and a shift of body fat. This shift in fat can lead to a round face, also called moon face. To avoid these side effects, steroids may be used only for short periods of time to control flare-ups. And other medicines that target the immune system may be used long term to control the disease.

Medicines that target the immune system. Some medicines can stop your immune system from attacking healthy tissues. Examples are azathioprine (Imuran, Azasan), mycophenolate (Cellcept) and cyclophosphamide. These too can have severe side effects, including an increased risk of infection.

Other medicines. If first line medicines aren't helping you, your healthcare professional may suggest another drug, such as dapsone, intravenous immunoglobulin or rituximab-pvvr (Ruxience). You may need antibiotics to treat infections.

Many people with pemphigus get better, especially if treatment is started early. But it may take years and can require taking medicine for a long time.

Where can I find out more information about pemphigus foliaceous?

The British Association of Dermatologists have a Patient Information Leaflet about PF. DermNetNZ is also a good source of further information about pemphigus foliaceus.

• Introduction
• How is OMMP diagnosed?
• Why may it be difficult to make a diagnosis?
• What should I do if my tests are negative?
• Why are my eyes so painful?
• Are there many people with OMMP?
• Can other parts of my body be affected?
• How am I going to be treated?
• Can I be cured?

Introduction

Mucous Membrane Pemphigoid (MMP) is an autoimmune disease which affects the skin and mucous membranes. When the eyes are affected, it is called ocular MMP (OMMP). The cause of MMP is not clearly understood, but it is known to have a genetic predisposition although this probably only plays a minor role. The disease is rarely associated with cancers when it is called paraneoplastic pemphigoid. Autoantibodies can be identified in most patients except for those with ocular only MMP (no other sites affected). The antibodies are directed at the subsurface layer (basement membrane) of the mucous membranes and, in some cases, of the skin causing inflammation and ulceration or blistering which lead to scarring. The scarring component is why the disease used to be called cicatricial pemphigoid. Another older term for the disease was "Benign MMP"; so called because it rarely causes death unlike pemphigus which historically had a high mortality, before the advent of immunosuppressive therapies. Although it can affect the skin it is only diagnosed when mucous membranes are involved. The mucous membranes targeted by the disease, for reasons that are not understood, are those at our orifices; mouth, eyes, nose, throat, genitals, anus and less often the tracheal region and oesophagus. MMP rarely affects all of these sites in any one person, more often 1-3 sites are involved. The most affected sites are the mouth (gums and oral mucosa) followed by the eyes, nose and throat and then other sites. When the eyes are affected both are usually involved.

The disease causes variable inflammation, often with ulceration and scarring at affected sites. Inflammation is usual at all sites and causes pain, as does ulceration, although the development of ulceration and scarring varies from site to site. For example, ulceration is common in the mouth but infrequent in the eyes whereas scarring is infrequent in the mouth but a hallmark of eye disease. Scarring does not cause pain but the effects of scarring may result in loss of function such as difficulty swallowing and speaking, or lead to ingrowing eyelashes and loss of tear production.

When the disease affects the eyes, it results in inflammation (conjunctivitis) and scarring of the conjunctiva. The illustration shows the conjunctiva which is the thin membrane (0.25 mm) that covers both the white of the eyeball and which extends into the sacs (fornices) behind the lids (a) and (b) and which lines the back surface of the eyelids to the lash margin (b). Conjunctival scarring occurs in the thin layer behind the surface (where it is called subepithelial fibrosis) and results in contraction with shortening of this large area of thin lining tissue causing loss of the fold of conjunctiva adjacent to the nose (the plica semilunaris) (c) and shortening of the fornices (d) followed by the formation of bands of tissue between the eyeball and eyelid called symblepharon (e). In more advanced cases this process results in the loss of all of the conjunctival tissue between the eyeball and eyelid, so that the two appear to have stuck together.

The shortening of the conjunctiva on the back surface of the lid may also cause the eyelid(s) to turn inward (called entropion) which often results in the lashes rubbing on the surface of the eye (called trichiasis). The conjunctival scarring may also cause damage to the accessory lacrimal (tear) glands in the conjunctiva, the mucous producing cells, and the very fine ducts that bring the tears from the lacrimal gland (situated under the outer end of the upper eyelid and eye socket) causing a dry eye.

OMMP progresses at different rates in different patients, a small proportion get a rapid onset of severe inflammation and scarring which can lead to blindness in months whereas in most patients the inflammation is initially mild and/or intermittent resulting in a slower onset over years. In both groups a lack of appropriate treatment can cause severe visual debility or even blindness. Diagnosis and appropriate treatment at an early stage can largely prevent or greatly slow down disease progression. Correct diagnosis, as quickly as possible.

How is OMMP Diagnosed?

For patients with MMP already diagnosed at other sites such as the mouth or nose, then disease is relatively easy to confirm or exclude in the eyes. This is because the disease at the non-ocular sites more often tests positive (in biopsies and blood) than when MMP is limited to the eyes. In patients, with known MMP at non-ocular sites, any eye inflammation (conjunctivitis) or any of the early signs of scarring (as in the illustration) must be assumed to be caused by ocular MMP and diagnosis without conjunctival biopsies is accepted by international guidelines. All patients with MMP at other sites should be referred to an ophthalmologist for an eye examination, whether or not they have these symptoms and signs of eye disease, because early signs of OMMP may be present without symptoms. If there are signs of inflammation or scarring needing treatment, as mentioned above, there is no requirement for further tests on the eyes to make the diagnosis of OMMP, providing the tests at any other sites have confirmed that MMP is present and that the eye signs are typical. However, the ophthalmologist may want the results of additional eye biopsies, or other investigations, to exclude other conjunctival scarring diseases that can co-exist with MMP or be confused with it.

For those patients with OMMP and no involvement of other sites (ocular only MMP) the path to diagnosis has been difficult and may continue to be so for a time as not all clinicians will be aware of the recently published (2021) European Guideline (European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part II E. Schmidt, H. Rashid, A. V. Marzano, A. Lamberts, G. Di Zenzo, G. F. H. Diercks, et al. J Eur Acad Dermatol Venereol 2021 Vol. 35 Issue 10 Pages 1926-1948); these give criteria for the diagnosis of ocular only MMP when both conjunctival and biopsies from other sites (typically skin or oral mucosa), as well as blood tests for autoantibodies, are all negative. There are over 20 causes of conjunctival inflammation and scarring although, in the UK, MMP is the most common of these. In addition, most of the other causes are associated with easily identified diseases with the exception of surface tumours (usually affecting only one eye whereas MMP usually affects both), sarcoidosis and other autoimmune bullous diseases (e.g. pemphigus); the latter may very rarely show up in the eye before developing at other sites. Diagnosis of ocular MMP requires one small (2-3 mm) biopsy, ideally from each eye, taken from the conjunctiva, often from the loose conjunctival tissue on the ball of the eye under the upper lid, using local anaesthetic eye drops, together with blood tests. It is optimal to take an additional biopsy from another site, even though there are no symptoms at that site, usually the mouth mucosa or the skin because these sites may test positive when the ocular samples test false negative. The eye biopsies are processed for both the direct immunofluorescence test (as are the biopsies from the apparently uninvolved sites) and for routine histopathology to exclude other potential causes of the inflammation and scarring. Blood is taken to detect pemphigoid antibodies using a variety of tests.

Why may it be difficult to make a diagnosis?

When MMP affects the eye, with no other sites of involvement, the tests described above, that have been considered necessary for diagnosis, are negative in about 50% of cases. Until the 2021 European Guideline was published (as described above) this caused a lot of problems for OMMP patients because effective treatment for OMMP requires quite different treatment than that for the other causes of scarring conjunctivitis, for which the standard of care is local treatment, often with steroid eyedrops. Unfortunately, local steroid eyedrops are ineffective at controlling the inflammation in OMMP and do not prevent the progression of the conjunctival scarring, both of which usually require oral, or intravenous, anti-inflammatory medication.

What should I do if my tests are negative?

It is now increasingly accepted by specialists in MMP (see the European Guidelines mentioned above) is that in OMMP, particularly when no other sites are involved by MMP, a diagnosis does not require positive test results but can be made after the tests have been used to exclude the other potential causes and using clinical findings. Your specialist should be told about the European Guidelines if you think you may have MMP affecting the eyes and your tests are negative.

Why are my eyes so painful?

The inflammation of the conjunctiva itself can be very painful and irritating. Inturned eyelashes (trichiasis) can also scratch the surface of the eye and damage the cornea, and dry eyes compound the discomfort.

Are there many people with OMMP?

MMP is a rare disease, occurring in about 2.5 per 100,000 in Europe.

Can other parts of my body be affected?

About 60-70% of MMP patients have some level of eye involvement in their condition. Half of these have OMMP without involvement of other sites and the remainder have MMP involving other mucous membranes such as mouth, nose, larynx, oesophagus and the genital and anus areas affected. It can also cause blistering on the skin. The degree of scarring varies by the location. You will probably be referred to a variety of medical specialists to monitor the extent of your disease.

How am I going to be treated?

About 20% of patients with MMP and ocular involvement have minimal inflammation with slowly progressive scarring and will need no treatment or simple topical therapies. However, topical treatments – those that you put directly in your eye – haven't been found to be effective in controlling inflammation or the progression of scarring in the other 80% of cases which require treatment with oral therapy. The ophthalmologist, or another specialist working with the ophthalmologist, will usually start treating milder cases with the least risky drugs – those with the least severe side effects - such as dapsone and sulfasalazine. But in cases where the disease progresses quickly, more "aggressive" (but better termed "effective") treatments will be deployed. These treatments may involve drugs such as steroids to get short term control of severe inflammation but which, to avoid steroid side effects, must be used with non-steroidal "immunosuppressive" drugs. Steroids are generally only needed for a few months while the immunosuppressive drugs take effect. These will reduce your immune system response and therefore the autoimmune activity which is causing the damage to your eyes. Commonly used drugs for moderate disease are: azathioprine, mycophenolate, and (occasionally) methotrexate.

If your eye disease is particularly severe then cyclophosphamide and steroids, or steroids before courses of intravenous "biological" anti-CD20 treatments (e.g. Rituximab or Truxima) or intravenous immunoglobulin (IVIG) will be used.

Where the disease has also caused entropion (the eyelids turning in) and the eyelashes are scratching the cornea, then you may be recommended to have the eyelashes removed (epilation) either in the clinic or by self-removal. For occasional individual lashes electrolysis may be useful. For large numbers of lashes, for which epilation has proved difficult to manage, both electrolysis and freezing therapy (cryotherapy) have been used in the past. However as these latter may cause increased lid scarring and disease flare ups respectively, they have been superseded by surgery to turn the eyelids out to reposition the lashes away from the eye or by surgery to totally remove all the lashes.

Can I be cured?

MMP and, specifically OMMP, are not curable. But with the right treatment at the right level, it is possible to halt the progress of the disease and "remission" can be achieved. It is vital that there is an early diagnosis and effective treatment is given to control inflammation and slow the progress of scarring. Currently, there is no reversing the blindness that very bad or untreated OMMP can cause with the exception of the use of artificial corneal replacements – treatments that carry a high risk of loss of all vision (no light perception) but which can offer the prospect of long periods of good vision. The best established of these treatments is the osteo-odonto-keratoprosthesis (OOKP) and its variants which should only be carried out in accredited centres.

Clinical variants of pemphigus and pemphigoid

Pemphigoid and pemphigus have a number of variations, all are rare. The variants covered here are even rarer. Some autoimmune diseases of the skin shown here are not categorized as pemphigus or pemphigoid, but some mimic symptoms of pemphigus and pemphigoid, therefore more research is needed. They are;

• Pemphigus Vegetans
• Pemphigoid Gestationis
• Paraneoplastic Pemphigus
• Lichen Planus Pemphigoid
• Linear IgA Disease
• Epidermolysis Bullosa Acquisita