Ministry of Health Protection of the Ukraine Zaporozhye state medical university Department of skin and venereal diseases
LESNITSKY A.I., MAKURINA G.I.
Bullous and Vesicular Dermatoses
Manual book for the students
Duhring’s dermatosis. the knowledge of this pathology is necessary for all the clinicians to render qualified help to the patients. The disease has a chronic character. simple vesicular lichens. Acantholysis underlies Nikolsky’s phenomenon: by pulling the covering of the vesicle. weakness of intercellular contacts and accumulation of exudate in this layer. If not treated the vesicles soon appear on the whole skin. the viral theory but it is not completely proved. the epidermis exfoliates outside the boundary of the vesicle on the healthy skin. Due to this. Treatment with corticosteroids reduces highly the severity of the disease. Recently autoimmune processes are considered to be of great importance in the pathogenesis: discovery of antibodies to intercellular substance in the skin. or their exudate gets covered by crust. infectionists). herpes zoster. Patients should consult not only dermatologists but also other specialists (physicians. in particular. in liquid of the vesicles and in blood serum.
Peculiarities of the course of pemphigus
The morphologic basis of development of vesicles in this disease is acantholysis – destruction of protoplasmic process of the cells of the epidermis stratum spinosum. serious disease. Its clinical manifestation is the formation of vesicles on non-inflamed skin and mucous membranes. Nikolsky’s symptom is more expressed in the stage of pemphigus exacerbation. due to which inter epidermal vesicle is formed. then open and form erosions. In immunofluorescence.
. dentists. continuous progress and in the absence of treatment soon results in lethal outcome. During severe scratching of the healthy skin between the vesicles the exfoliation of the epidermis takes place. exudative multimorphic erythema).
Etiology and pathogenesis of pemphigus
There are different etiopathogenic theories. The vesicles appear suddenly on the healthy skin or mucosa. in intercellular space of stratum spinosum of epidermis immunoglobulin G is found only in the patients with pemphigus.
True (acantholytic) pemphigus
Pemphigus is a malignant.Bullous and Vesicular Dermatoses
The group of vesicular and pemphigus dermatoses includes different diseases on the basis of etiology and pathogenesis (pemphigus.
after which. Usually dermatosis begins with affection of the oral and throat mucosa (Fig.Clinical varieties
Four forms of true pemphigus are differentiated: pemphigus vulgaris (common). septic fever sets in and is particularly severe if secondary infection develops. inguinal region. stratified brownish crusts are formed. spontaneous remissions alternate with recurrences. retention of sodium and chlorides in the tissues and a diminution in the protein content. pemphigus vegetans. as a rule. and are filled first with clear and later on with thick serous fluid. 2). eroded surfaces with polycyclic contours are formed rapidly in the process of evolution. which then rub off. Typically the course is severe and chronic. lungs and heart may develop. after which brown pigmentation remains on the areas of the foci. In other cases (when the process tends to spontaneous remission or under the effect of steroid therapy). the tops of the bullae remain intact. limbs. As a rule. The lesions are particularly painful when located in the mouth. on the lips. there are also eosinophilia. They range in size from a pea to a bean but may be larger. and they gradually collapse and turn into a thin crust. which intensifies when clothes are changed or when the patient alters position. because the exudate resolves. face and external genitals is involved in the process. axillae. kidneys.
This form of pemphigus accounts for approximately 75 per cent of the total number of all forms of pemphigus (Fig. pemphigus foliaceus (exfoliative) and seborrheal pemphigus.
Fig. 1. the skin of the trunk.
. The disease sets in suddenly with the abrupt appearance of bullae on an apparently healthy skin. the organism becomes exhausted. There may be changes in the blood protein fractions and in the content of immunoglobulins A. Intercurrent] diseases of the liver. Patients died within a few months to two years in the precorticosteroid era. 1). Pemphigus vulgaris Weeping. and the genitals. In regeneration of the epidermis. In a malignant course. In a benign course of the process the patient's general condition hardly changes. Sometimes the numerous erosions cause severe pain. The bullae are at first tense and then rapidly become flaccid. Patients suffering from pemphigus usually experience no itching. G and M.
however. Pemphigus vulgaris located on the lips The degenerative changes in the Malpighian layer. From the very onset of the disease. under the mammary glands. It is positive in almost all pemphigus patients in the phase of exacerbation. because it also occurs in other dermatoses (particularly in congenital epidermolysis bullosa. and finally. Papulomatous growths (Fig. it cannot be regarded strictly pathognomonic for true pemphigus. Pemphigus vegetans
. whereas the use of maintenance steroid therapy prolongs the patients' life for many years after the disease. Besides.
Fig. This last diagnostic test in pemphigus is called the Asboe-Hansen's sign. but may be negative in other periods of the disease. 2. when apparently healthy skin areas remote from the foci of affection are rubbed. when an intact bulla is pressed with a finger one can see the fluid separating the adjacent epidermal areas and the bulla enlarging on the periphery. Nikolsky's sign is often positive. Modern methods of treatment make it possible to delay considerably the onset of recurrences in many such patients. the navel and in the region of the large skin folds (axillary. inguinofemoral. the epidermis on the apparently healthy skin is separated. behind the ears).
At the beginning of its development this form of pemphigus is clinically similar to pemphigus vulgaris and often starts with the appearance of lesions on the oral mucosa. intergluteal. Ritter's disease. Despite the high diagnostic value of Nikolsky's sign. Active movements are difficult because of sharp pain. attention is drawn to the tendency of the bullae to be localized around the natural orifices. 3) secreting a considerable amount of exudate are formed later in places of the ruptured bullae against the background of an eroded surface covered with a dirty film. 3. which are embraced by the term 'acantholysis' are the morphological base of a significant clinical and diagnostic sign known as Nikolsky's sign (phenomenon).Fig. the upper layers of the epidermis are easily injured. the upper layers of the epidermis are also separated. The dermatosis is accompanied with pain and a sensation of burning. Lyell's syndrome). when the apparently healthy skin area between the bullae or erosions is rubbed. The lesions tend to coalesce and form large vegetative surfaces at places with purulent necrotic disintegration. It may be described as follows: If one pulls the ruptured top of the vesicle.
including the erythrodermic type. As it advances. The patients gradually become weaker. producing a scaly surface. while in generalized lesions. In some patients with pemphigus vegetans. it deteriorates (particularly in children) with a rise in body temperature (which is at first subfebrile and then febrile). and advancement of anemia and eosinophilia. by which the disease is also known. including the scalp (the hair often falls out). dermatosis gradually occupies extensive areas of the skin. New portions of the exudate cause the layering of these crusts. cachexia grows and death may occur. It is in this variant of pemphigus that the sign described by Nikolsky in 1896 is always sharply positive. and often develops along the type of erythroderma (Fig. Epithelization of erosions under the crusts is slow. which later turn into bullae. Marked pigmentation remains after the lesions. Pemphigus foliaceus is encountered more often than the vegetans form among adults and prevails over other variants of pemphigus vulgaris in children. More frequently the tops of the bullae dry up into thin stratified scaly crusts. flaccid bullae with a thin top and slightly elevated above the surface form on apparently healthy skin. The severity of disorders in the general condition is determined by the extent of the skin affections: when there are few foci the general condition is hardly disturbed.If treatment is successful.
The disease is characterized by drastic acantholysis leading to the formation of superficial fissures directly under the horny layer. At the beginning of the disease. 22). The oral mucosa is very rarely involved in pemphigus foliaceus.
. They rupture rapidly with the formation of large erosions. disorders of water and salt metabolism. hence there is a term 'exfoliative'. lose weight and cachexia develops. A chronic course for many years with periods of spontaneous improvement is characteristic of pemphigus foliaceus. the vegetations become flatter and drier and the erosions epithelize.
sharply outlined ring of homogeneous protoplasm. The bullae are often formed unnoticeably and the crusts seem to be primary lesions. is the fundamental histopathological change in all the forms of true pemphigus.Pemphigus seborrhoicus. 4. first there develop fissures and then bullae whose cavity is penetrated by cells and groups of cells (neutrophils. though of a long duration.
Fig. to a smaller extent. Closely arranged greasy crusts are formed against an erythematous background and simulate the picture of cicatrizing erythematosis on the face. eosinophiles and. 4). close to them and. Moist eroded surfaces are exposed when the crusts are removed. In most cases. These cells are smaller than the normal cells of this layer and
. Thus it becomes clear that in such patients Nikolsky's sign may be positive almost on any area of the skin. Acantholysis creates grounds for the subsequent formation of bullae. luminescence is seen both in the intercellular substance of the prickle-cell layer and in the basal membrane in the region of the dermoepidermal boundary. The lesions usually first appear on the face and less frequently on the scalp. In other forms of pemphigus it is mainly positive in places where the bullae are formed. In patients with pemphigus erythematosus. they are a bad prognostic sign. chest and back. the disease is benign. less frequently. the cells themselves are swollen. however. which are always located between the cells of the prickle-cell layer. It is particularly sharply marked in pemphigus foliaceus and is revealed even on areas of seemingly healthy skin. disruption of the connections between the epidermal cells. in places remote from the bullae. Acantholytic cells are seen in impression smears from these surfaces. their nuclei are round. Acantholysis. Lesions rarely occur on the mucous membranes. in sites characteristic of seborrhea. Some of the cells of the prickle-cell layer undergo degenerative changes. lymphocytes and histiocytes). or erythematosus (Senear-Usher syndrome)
Pemphigus seborrhoicus belongs to the group of true pemphigus because the possibility of its development into the foliaceus or vulgaris variant has been authentically proved (Fig. Senear-Usher Syndrome Histopathology. but if this happens. hyperchromatic and are surrounded with a narrow. As a consequence of the destruction of the intercellular bridges in the lower parts of the Malpighian layer. In other cases vesicles covered with stratified yellowish crusts are formed on the trunk and limbs.
monomorphic character of eruptions. methotrexate. the hormones have been recently successfully combined with the prescription of cytostatic drugs. Duhring's disease. The task of the physician in management pemphigus consists in 'titrating' such a dose of the hormone which would be minimum for the given patient and would not give rise to a recurrence of the disease. the dose of corticosteroids may be reduced. It is often easy to diagnose pemphigus vulgaris due to its frequent onset with involvement of the oral mucosa. In individual cases medication with corticosteroid hormones can be completely discontinued after minimum doses have been taken for several years. 4-6 mg of dexamethasone daily). 25 mg taken daily for 5 days followed by a 3-day
. positive Nikolsky's sign. Children are sometimes prescribed ACTH in a daily dose of 10-20 U. for children whose ages range from 5 to 15 years the daily dose of prednisolone should not exceed 10-20 mg. however. but very slowly (to avoid exacerbation of the process and prevent the 'phenomenon of steroid drug discontinuation'). increase sharply with the considerable increase of steroid doses. In such cases the doses of the drug are gradually increased until the desirable therapeutic result is obtained. Treatment with steroid hormones envisages the prescription of maximum doses (40-60 mg of prednisolone or methylprednisolone. which are of high diagnostic significance. congenital epidermolysis bullosa and the bullous form of lupus erythematosus). For instance. In order to reduce the dose of corticosteroid hormones and in this way to avoid the severe complications. 100 mg infused intravenously every day. i. which at times are even hazardous to the patient's life. total treatment dosage 2000-2500 mg. Sometimes. These are acantholytic Tzanck cells. The diagnosis of true pemphigus does not present much difficulty in “classical” cases. that of triamcinolone should be no more than 8-12 mg. The important tests for verifying the diagnosis are detection of acantholytic cells in impression smears or in Giemsa-stained smears (cytodiagnosis by Tzanck) and the demonstration of fluorescence in the region of the intercellular spaces of the prickle-cell layer in response to anti-IgG by means of immunofluorescence. 32-48 mg of triamcinolone. The cytoplasm has a light-blue zone around the nucleus while on the periphery it is stained an intensive blue colour. particularly in differentiating the bullae in pemphigus from those in Duhring's disease. is necessary when there are vital indications. The prescription of large doses of corticosteroids. although the number and severity of complications.possess large darkly stained nuclei containing two or three large nucleoli. When new eruptions cease to appear and exudative phenomena in the foci diminishes. In children these doses are reduced according to age. even large doses of steroids are insufficient to arrest the pemphigoid process. relatively slow advancement of the disease. however. and the maximum dose of dexamethasone 2-3 mg. toxicoderma bullosa. These are called minimum maintenance doses and patients with pemphigus must continue to take them constantly after discharge from the clinic. 25 mg injected intramuscularly once in 5-7 days to a total of 4 or 5 injections or half a tablet is taken orally four times a day. to stimulate the adrenal cortex. The following cytostatics (immunosuppressants) are used: prospidium chloride. which they may induce. and the increasing deterioration of the general condition. Pemphigus vegetans is also characterized by intraepidermal eosinophilic abscesses.e. All this allows pemphigus to be differentiated from abruptly developing bullous skin lesions (erythema exudativum multiforme.
vitahepancreatine. Flucinar. taken for 3 to 4 weeks after which the daily dose is gradually reduced to 50 mg. syn.). discovery of immunoglobulin G during immunofluorescence in the intercellular space of the stratum spinosum). bullous toxicoderma (Lyell’s syndrome) and Duhring’s dermatosis (Fig. positive Nikolsky’s symptom. riboflavin. Oxycort. calcium and vitamins. which actually takes place in most cases as a result of corticosteroid therapy. 5).. Secondary coccal infection is prevented by prescribing frequent warm baths with disinfectant solutions (e. Differential diagnosis is carried out with multiform exudative erythema.
Diagnosis and differential diagnosis
To make a diagnosis. Dermasolone. Senthol containing prednisolone with potassium. folic acid). etc. 1-2 per cent aqueous pyoktanin solution. The diet of patients with pemphigus should contain a low amount of table salt and carbohydrates but must include high-calorie proteins. vitamins and methylandrostenediol may be prescribed. Antibiotics are given (orally and in injections) if secondary infection develops.). The affected skin areas may be smeared with corticosteroid ointments (Locacorten. methylandrostenediol. ascorutin. agents stimulating phagocytosis (pentoxyl. the clinical signs (often starts on the mucous membrane of the mouth.g. administration of liver preparations (heparin. calcium pantothenate. syn. injection of gamma-globulin. crystal violet. infusions of native plasma (also 150-200 ml). The physician and attendant personnel should constantly assure the patient of his imminent recovery. It is essential to wash the mouth thoroughly after every meal (a mouthwash with calendula or 1:5000 nitrofurazone solution). rutin. calcium. progressive disease). salt and protein metabolism. treatment lasts 4 to 6 months. monomorphic vesicles. examination of the blood and urine characterize the upset of water. 5 per cent boric acidnaphthalan ointment. etc. calcium and potassium preparations. potassium permanganate) followed by application of disinfectant agents (Castellani's paint.). Depending on the patient's condition it consists of blood transfusions (150-200 ml preferably by drip). Hyoxisone. methyluracil) and vitamins (ascorbic acid. Proper and thorough care of a patient is of paramount importance when the affection occupies extensive skin and mucosal areas. etc. Azathioprinum (Imuran) is prescribed orally in a daily dose of 200 mg. Metandienone. Nerobolil. hepavit tablets) and autohemotherapy.) and irrigated with aerosols containing corticosteroid and antibacterial agents (Oxycyclosole. antianaemin (2-4 ml injected intramuscularly daily or every other day).interval (a total of 4 or 5 such courses are given). etc.
. Patients with pemphigus must also be given anabolic hormones (methandrostenolone. laboratory findings (discovery of Tzanck acantholytic cells in the smear from the erosion. Symptomatic therapy is very important.
grouped Very rare. Negative Usually intense Relapsing More favourable. papule. i. soon heals Subepidermal Polymorphic Geometric. exists for 7-10 days Often less. macula. in severe cases may be lethal Dermatitis herpetiformis (Duhring’s disease) Vesicles.Fig. rare transformation into pemphigus Not discovered Causes intensification Frequent in blood (20-30%) Nearly always high in vesicle Marked in many cases
Tzanck acantholytic cells Discovered Reaction with iodine Absent Eosinophilia Not high in blood. rare in vesicles Therapeutic effect Absent
. without the tendency towards epithelization Intraepidermal Monomorphic Unsystematic In most patients the disease often starts in the mouth cavity Positive Rare Continuos course Serious. bulla.e. pustule (polymorphism) The cover is dense. does not start in the mouth cavity. 5. Dermatitis herpetiformis (Duhring’s disease) Differential sign Primary elements Character of lesions Erosion Localization of the vesicle Character of the elements Localization of elements Infection of the mouth cavity Nicolsky’s symptom Itch Course Prognosis Acantholytic pemphigus Vesicles on the healthy skin Flaccid. thin cover soon opens Often extensive.
What are the clinical peculiarities of pemphigus vulgaris. In the suspicion of Duhring’s dermatosis test with iodine preparations (Ydason’s test) is performed. In suspicion of this disease smears from the exudate (vesicle fluid) are checked to reveal the increased quantity of eosinophiles. Complaints (intense pain in herpes zoster. b) At the time of examination pay attention to the distribution of the dermatosis and its preferred localization. 6. presence of accompanying diseases. 2. monomorphism or polymorphism of the lesions. 3. immunofluorescence (presence of immunoglobulin G in the intracellular space of the stratum spinosum in pemphigus. General and external treatment of the patients is prescribed individually depending on the nosologic form of dermatosis. Get acquainted with the methods of the treatment in the surgery.). presence of immunoglobulin A in the basal membrane in Duhring’s dermatosis) can be carried out. Check Nikolsky’s symptom. and prognosis. 3. c) Laboratory examination: in blood analysis pay attention to eosinophilia (Duhring’s dermatosis). The student should know the indications and contraindications of corticosteroids and other medicaments to be able to prescribe the drugs. What do we call acantholytic cells? The method of preparation of the smears. age of the patient. 5. Why are cytostatics used in the treatment of pemphigus? 9. a) History-taking. Differential diagnosis.Practical part
1. In suspicion of pemphigus smears from newly opened vesicle are checked for the presence of acantholytic cells. The causes of the Nikolsky’s symptom. its diagnosis and the importance in vesicular dermatosis. their localization. List the basic primary and secondary lesions. vegetans. foliaceus and seborrheic? 7. Methods of examination of patients with vesicular dermatosis. character of vesicles. Characterize the general progress of the disease. time of the emergence of lesions and their development. treatment received and its effect.Why are drugs of potassium and anabolic hormones given with high doses of corticosteroids?
. What do the immunofluorescence and the shining of intracellular substance prove? 8. Modern theories of etiopathogenesis of pemphigus. The final diagnosis is made. 2. etc. Why is the permanent treatment with corticosteroids given during pemphigus? 10. What is acantholysis? 4. Treatment.
1. The differential diagnosis is made for every patient taking into account the above mentioned signs (see theoretical part). possible complications. Additionally. itch in Duhring’s dermatosis.
11. 12.List the possible complications of corticosteroid therapy. 15.Name the basic and most effective drugs in the treatment of patients with Duhring’s dermatitis. 14. which are of importance for diagnosis in Duhring’s dermatitis.List the primary morphological lesions in this disease.
.Which etiopathologic theories of Duhring’s dermatitis are known? 13.List the basic signs.