Pemphigus vulgaris is a chronic blistering skin disease with skin lesions that are rarely pruritic, but which are often painful.
Pathophysiology
It is an
autoimmune diseaseAutoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
caused by
antibodiesAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
directed against both
desmoglein 1Desmoglein 1 is a protein that in humans is encoded by the DSG1 gene.-Interactions:Desmoglein 1 has been shown to interact with PKP3 and PKP2.-Further reading:...
and
desmoglein 3Desmoglein-3 is a protein that in humans is encoded by the DSG3 gene.-Interactions:Desmoglein 3 has been shown to interact with PKP3.-Further reading:...
resulting in the loss of cohesion between
keratinocyteKeratinocytes are the predominant cell type in the epidermis, the outermost layer of the human skin, constituting 95% of the cells found there. Those keratinocytes found in the basal layer of the skin are sometimes referred to as "basal cells" or "basal keratinocytes"...
s in the
epidermis. It is characterized by extensive flaccid blisters and mucocutaneous erosions. The severity of the disease, as well as the mucosal lesions, is believed to be directly proportional to the levels of desmoglein 3. Milder forms of
pemphigusPemphigus is a rare group of blistering autoimmune diseases that affect the skin and mucous membranes.In pemphigus, autoantibodies form against desmoglein. Desmoglein forms the "glue" that attaches adjacent epidermal cells via attachment points called desmosomes...
(like foliacious and erythematoses) are more desmoglein 1 heavy. It arises most often in middle-aged or older people, usually starting with a blister that ruptures easily. The lesions can become quite extensive. The pathogenesis of the disease involves autoantibodies against
desmosomeA desmosome , also known as macula adherens , is a cell structure specialized for cell-to-cell adhesion...
proteins, separating keratinocytes from the basal layer of the epidermis. On histology, the basal keratinocytes are usually still attached to the
basement membraneThe basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
leading to the appearance and thus the term, "tombstoning".
Transudative fluidTransudate is extravascular fluid with low protein content and a low specific gravity .This is in contrast to transudate where the extracellular fluid is an ultrafiltrate of blood plasma and thus larger molecules such as proteins and cell debris are absent....
accumulates in between the keratinocytes and basement membrane (suprabasal split), forming a blister. This is a contrasting feature from
bullous pemphigoidBullous pemphigoid, also referred to as BP, is an acute or chronic autoimmune skin disease, involving the formation of blisters, more appropriately known as bullae, at the space between the skin layers epidermis and dermis.-Signs and symptoms:...
, where the detachment occurs between the
epidermis and
dermisThe dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
(subepidermal bullae).
Diagnosis
On a physical exam, pemphigus vulgaris has flat bullae and a positive
Nikolsky's signNikolsky's sign is a clinical dermatological sign, named after the Russian physician Pyotr Nikolsky . The sign is positive when slight rubbing of the skin results in exfoliation of the outermost layer....
. The gold standard for diagnosis is a punch biopsy of the lesion with direct
immunofluorescentImmunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
staining, showing
acantholytic cellAcantholysis is the loss of intercellular connections, such as desmosomes, resulting in loss of cohesion between keratinocytes, seen in diseases such as pemphigus vulgaris. It is absent in bullous pemphigoid, making it useful for differential diagnosis....
s. These can also be seen on a Tzanck smear. These cells are basically rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion protein:
DesmogleinThe desmogleins are a family of cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another....
.
Pemphigus vulgaris is easy to confuse with
impetigoImpetigo is a highly contagious bacterial skin infection most common among pre-school children. People who play close contact sports such as rugby, American football and wrestling are also susceptible, regardless of age. Impetigo is not as common in adults. The name derives from the Latin impetere...
and
candidiasisThrush redirects here. For the hoof infection see Thrush .Candidiasis or thrush is a fungal infection of any of the Candida species , of which Candida albicans is the most common...
. IgG4 is considered pathogenic. The diagnosis can be confirmed by testing for the infections that cause these other conditions, and by a lack of response to
antibioticAn antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
treatment.
Treatment
CorticosteroidCorticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s and other immunosuppressive drugs are the mainstay of treatment. Based on recent studies, corticosteroids can be used in Pulse Therapy/Supra-pharmacological doses once a month to decrease Hypothalamo-pituitary axis inhibition. IVIg,
rituximabRituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
,
mycophenolate mofetilMycophenolate mofetil is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis, which is necessary for the growth of T cells and B cells...
,
methotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
,
azathioprineAzathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
, and
cyclophosphamideCyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
have also been used with varying degrees of success. It is a difficult disease to control.