Blisters (flaccid vesicles and bullae) [13] may be a rare finding on examination. The blisters rupture easily because the superficial skin overlying the blisters is quite thin. A positive Nikolsky sign implies an acantholytic condition and is found when exfoliation occurs when rubbing the healthy skin. This was discovered in 1896 by Dr. Piotr Nikolsky [1]. Bullous pemphigoid forms blister between the epidermis and dermis which result in a thicker skin and are negative for Nikolsky sign. Also, in PF there is little to no involvement of the mucous membranes where pemphigus vulgaris affects the skin and mucous membranes.

Well-demarcated, erythematous, crusted lesions are more common. These lesions are very superficial. Blisters and crusts are found on the upper torso early in the disease and spread to the face and scalp. Mucosal involvement is a rare finding. The blisters are usually painless but the open lesions may cause a focal, burning pain. These symptoms are usually not debilitating. The pemphigus erythematosus variant tends to affect the malar region of the face.

• Pain

  Our patient is an 83-year-old female with a recent diagnosis of pemphigus foliaceus, who presented with painful ulcerations while on corticosteroids. Histopathology examination revealed disseminated herpes simplex virus (HSV). [ncbi.nlm.nih.gov]

  A note from Cleveland Clinic Pemphigus foliaceus is a skin condition that can cause painful and itchy blisters and sores on your skin. [my.clevelandclinic.org]

• Hodgkin Lymphoma

  Pemphigus foliaceus (PF), an autoimmune skin disorder resulting in the formation of superficial blisters, is a rarely reported skin manifestation of non-Hodgkin's lymphoma (NHL). [ncbi.nlm.nih.gov]

  Background: Pemphigus foliaceus (PF), an autoimmune skin disorder resulting in the formation of superficial blisters, is a rarely reported skin manifestation of non‐Hodgkin's lymphoma (NHL). [tandfonline.com]

  Although it was initially approved for use in B-cell non-Hodgkin’s lymphoma, a growing number of reports have described the efficacy of rituximab for B-cell depletion in the treatment of autoimmune diseases. 5 The mode of action of rituximab in autoimmune [mja.com.au]

  Pemphigus erythematosus (breast skin) Pemphigus vulgaris (breast skin) Images hosted on other servers: Paraneoplastic pemphigus Paraneoplastic pemphigus associated with non-Hodgkin lymphoma Pemphigus vegetans Pemphigus vulgaris Microscopic (histologic [pathologyoutlines.com]

• Swelling

  If you notice a yellow or white fluid or a yellow crust forming around your blister along with swelling and pain on your skin, contact your provider. [my.clevelandclinic.org]

  If you’ve been diagnosed with pemphigus already, you should contact your doctor if you develop: new blisters or sores a rapid spread in the number of sores fever redness or swelling chills weakness or achy muscles or joints Some people get better without [healthline.com]

• Weakness

  […] taking these medications it is only for a short period of time because if you use them long term they can have some negative side effects like an increased risk of developing cataracts and osteoporosis, which is a disease where your bones start to become weak [mddk.com]

  If you’ve been diagnosed with pemphigus already, you should contact your doctor if you develop: new blisters or sores a rapid spread in the number of sores fever redness or swelling chills weakness or achy muscles or joints Some people get better without [healthline.com]

  Complications of Treatment Immediate and long-term complications of DCP have been assessed in 136 patients. [77] Although flushing was the commonest immediate complication observed in 53.4% patients, weakness was the commonest long-term complication experienced [ijdvl.com]

• Burning Pain

  The blisters are usually painless but the open lesions may cause a focal, burning pain. These symptoms are usually not debilitating. The pemphigus erythematosus variant tends to affect the malar region of the face. [symptoma.com]

  Together these features contribute to frequent diagnostic delay.2 Patients complain of burning, pain, and puritis.1 While PF is less severe than other blistering disorders, significant morbidity and mortality results if left untreated.2 Pemphigus foliaceus [practicaldermatology.com]

  Scaly, inflamed, painful patches on the skin. These patches occur after blisters burst. Some people may only notice symptoms after the blisters burst. Burning, pain, and itching at the site of the blisters. [medicalnewstoday.com]

• Hoarseness

  Lesions may extend to cause hoarseness. Eating and drinking may become very uncomfortable. Other mucous membranes (conjunctivae, oesophagus and genitalia) may be involved. [patient.info]

  Sites often overlooked include around the nails (manifest as painful, red, and swollen), the pharynx and larynx (pain on swallowing and hoarseness), and the nasal cavity (nasal congestion and a bloody mucous discharge, particularly noticeable upon blowing [pemphigus.org]

  In children, ask about cough, chest pain, hoarseness, or difficulty swallowing (symptoms of thymoma; thymoma in adults is usually asymptomatic early on.) [dermatologyadvisor.com]

  Mucosal involvement may cause pain, difficulty swallowing, weight loss, nose bleeds and hoarseness. Side‐effects from treatment are common. [dx.doi.org]

• Nasal Congestion

  Sites often overlooked include around the nails (manifest as painful, red, and swollen), the pharynx and larynx (pain on swallowing and hoarseness), and the nasal cavity (nasal congestion and a bloody mucous discharge, particularly noticeable upon blowing [pemphigus.org]

• Oral Ulcers

  Clinical Indications and Features of Pemphigus Subtypes Subtype Indications and Features Pemphigus vulgarisa Fragile, flaccid bullae that evolve into erosions, crusting, Nikolsky sign; oral ulcers are commonly an initial presenting symptom Three forms [arupconsult.com]

  Clinical Features Pemphigus Vulgaris The oral mucosa is often the first site of involvement. Typically patients will have had multiple oral ulcers (broken blisters) that persist for weeks to months. [pemphigus.org]

  Ask about possible signs of systemic lupus, including oral ulcers, photosensitivity, arthritis, seizures or psychosis, and/or chest pain indicating possible serositis. [clinicaladvisor.com]

• Blister

  […] antibodies coordinately contribute to blister formation in PF. [ncbi.nlm.nih.gov]

  Blisters (flaccid vesicles and bullae) may be a rare finding on examination. The blisters rupture easily because the superficial skin overlying the blisters is quite thin. [symptoma.com]

  The result is the surface keratinocytes separate from each other, and are replaced by fluid: the blister. Because the blister is very close to the surface of the skin, the blisters rupture easily. [dermnetnz.org]

• Nikolsky's Sign

  Nikolsky's sign was positive. Prior to present consultation, he had taken prednisolone 40 mg tablet, once a day along with supportive therapy with which he had only partial relief. [e-ijd.org]

  It is manifested clinically by involvement of healthy-appearing skin that blisters when rubbed (Nikolsky sign). PF usually does not involve mucous membranes. In 1844, Pierre Louis Alphee Cazenave reported the first authenticated description of PF. [imagejournals.org]

  A positive Nikolsky sign implies an acantholytic condition and is found when exfoliation occurs when rubbing the healthy skin. This was discovered in 1896 by Dr. Piotr Nikolsky. [symptoma.com]

  The mucosal membranes were respected (fig 1), and Nikolsky’s sign was positive. Histological studies of a lesion showed splitting of the upper epidermis. [adc.bmj.com]

• Dermatitis

  Atopic dermatitis Seborrheic dermatitis Scarlet fever Staphylococcal scalded skin syndrome Stevens-Johnson syndrome Toxic epidermal necrolysis Toxic shock syndrome Generalized contact dermatitis Lichen planus Pityriasis rubra pilaris Drug hypersensitivity [visualdx.com]

  Abstract We describe a patient with paraneoplastic pemphigus who presented with erythrodermic lichenoid dermatitis, later developing blisters of pemphigus foliaceus type and oral erosive lesions. [ncbi.nlm.nih.gov]

  […] b c d e f g h i j k l m n o p q r s t u v w x y z by localisation Pemphigus Foliaceus definition Clinically less severe, and histologically more superficial immunobullous disease than pemphigus vulgaris characterized by pruritic, burning, or painful dermatitis [dermis.net]

• Ulcer

  Despite adequate treatment with anti-herpetic treatment, some ulcerations failed to heal. A second biopsy revealed the presence of cytomegalovirus (CMV). This was treated successfully with appropriate antiviral therapy. [ncbi.nlm.nih.gov]

  Treatment may involve: Antibiotics and antifungal medicines to control or prevent infections Fluids and electrolytes given through a vein (IV) if there are severe mouth ulcers IV feedings if there are severe mouth ulcers Numbing (anesthetic) mouth lozenges [mountsinai.org]

  Bhattacharya* A 72 year old gentleman, known to have Diabetes mellitus, Hypertension and Ulcerative colitis, was admitted to the Kothari Medical Centre, Kolkata, India, in October 2015 manifesting bullous lesions and erythroderma all over the body for [imagejournals.org]

  Antibiotics may be prophylactically administered to any blisters or ulcers to prevent infection. If the condition is widespread or severe the patient may require admission to a hospital to stabilize their condition. [symptoma.com]

  Crusted ulcerations on scalp and torso. A few bullae located on chest. There were no oral lesions. Labs Non-fasting glucose elevated at 632mg/dL. Culture of right cheek was negative. [practicaldermatology.com]

• Eczema

  A 55-year-old woman presented after a four-year history of impetiginized eczema that was distributed over her face, scalp, chest, and back and a recent diagnosis of breast cancer. [ncbi.nlm.nih.gov]

  Type I (3) Drug Eruption (56) Erythrodermia, Primary (1) Nummular Eczema (50) Pemphigus Seborrhoicus (13) Psoriasis Vulgaris, Chronic Stationary Type (72) Psoriatic Erythroderma (8) Sezary Syndrome (15) Staphylococcal Lyell's Syndrom (8) Subacute Cutaneous [dermis.net]

  Cancer, Sunscreen Warnings, Acne, Aesthetic Mishaps, Eczema View Issue [practicaldermatology.com]

  Types & treatments Childhood eczema Adult eczema Insider secrets Types of hair loss Treatment for hair loss Causes of hair loss Hair care matters Insider secrets What is psoriasis Diagnosis & treatment Skin, hair & nail care Triggers Insider secrets What [aad.org]

  Abstract A 55-year-old woman presented after a four-year history of impetiginized eczema that was distributed over her face, scalp, chest, and back and a recent diagnosis of breast cancer. [escholarship.org]

• Withdrawn

  Treatment was then changed to oral mycophenolate mofetil, which continues, and corticosteroids were slowly withdrawn. Despite the presence of detectable antibody (with a titer of 1:5 to 1:80), the patient remains well. [nejm.org]

  A complete remission was achieved in four weeks, and prednisolone was withdrawn. The child has been in complete remission since dapsone withdrawal, with a follow up of nine months. No circulating autoantibodies are currently detectable. [adc.bmj.com]

  The patient enters phase 2 when complete disease remission is achieved and intervening corticosteroids are completely withdrawn. The patient continues to receive DCP along with daily oral cyclophosphamide 50 mg for 6 or 9 more months. [ijdvl.com]

If pemphigus foliaceus is suspected, there are a variety of diagnostic studies that may be performed. However, these tests are rather invasive and require skin biopsies or blood samples. The biopsies are evaluated histologically and by direct immunofluorescence (DIF).

• Skin biopsies are required from two sites: A perilesional biopsy and a biopsy from an affected region. The perilesional skin should be adjacent to the biopsied lesion. The inflamed skin may result in the destruction of autoantibody deposits and result in a false-negative study [14].
• Patient serum may also be analyzed using enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence [15].

Diagnosis of PF is based on three criteria. No one condition is sufficient for diagnosis.

1. History and physical exam.
2. Histopathological findings of the affected skin biopsy and perilesional biopsy.
3. The presence of autoantibodies in a biopsy of the affected skin by DIF or via indirect immunofluorescent studies of the patient’s serum.

• HLA-DR4

  Pemphigus is more common in persons with certain HLA allotypes. HLA DR4 and DR14 (DRB1*0402 and DRB1*0401 more specifically) crucial in susceptibility. [pemphigus.org]

  […] pemphigus, pemphigus foliaceus is caused by immunoglobulin G (IgG) antibodies directed against desmoglein-1 (Dsg1) found in the granular layer of the epidermis.[1][2] Etiology Susceptibility to pemphigus foliaceus has been correlated with the presence of HLA-DR4 [ncbi.nlm.nih.gov]

Pemphigus disease is rare. There is insufficient evidence to develop a consensus in regards to treatment guidelines. Many treatment regimens are based on small case studies or physician experience.

The first line of intervention is least invasive: rest, stress reduction, and a thorough medication review. Any medication that is a potential trigger (especially sulfa drugs) should be discontinued and replaced with a different class of medication. Also, any blisters and open sores should be dressed appropriately. Antibiotics may be prophylactically administered to any blisters or ulcers to prevent infection.

If the condition is widespread or severe the patient may require admission to a hospital to stabilize their condition. Severity is determined by the ratio of blistered or ulcerated skin to the amount of healthy tissue. Critical cases are rare, but in these cases, the first line medical treatment is oral prednisolone dosed at 1mg/kg/day. The administration of high doses of corticosteroids for prolonged periods of time will result in detrimental side effects including hyperglycemia, insulin resistance, leukocytosis, and osteoporosis. These conditions must be anticipated and managed. Alternatively, steroid sparing agents can be used to minimize the negative effects of prolonged, high-dose steroids.

No single medication has been shown to be superior to others. Drug choice will depend on a variety of factors including severity of the condition, past medical history, and the physician’s medical judgment.

Options include agents such as:

• Minocycline/doxycycline
• Immunosuppressive agents (such as azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, and methotrexate): oral or intravenous administration may be effective. Intravenous treatment is reserved for severe cases.
• Immunomodulators (such as human intravenous immunoglobulin therapy and plasmapheresis): the goal of these therapies is to reduce the amount of circulating autoantibody.
• Dapsone [16]: dapsone alone may be sufficient to treat mild cases of pemphigus foliaceus. It may also be used in pediatric cases.
• Biologic response modifiers (such as intravenous rituximab [17]): this class of medication downgrades the immune response.

Generally, patients with pemphigus foliaceus have a good prognosis, if the disease is adequately controlled. Spontaneous remission is possible; however, patients usually require long-term immunosuppression [12]. Patients with incomplete treatment (i.e., those who have multiple remissions) can develop a more aggressive disease. This process is called disease-hardening, where an indolent disease becomes aggressive and resistant to treatment.

The exact mechanism of PF is not known. Autoantibodies against desmosome result in the pathognomonic blisters. Immunoglobulin type G (IgG) is the most common antibody involved in most cases of PF. In immunoglobulin A (IgA) pemphigus foliaceus, the pathologic autoantibodies are comprised mainly of the immunoglobulin type A. Research is underway to clarify the mechanism that leads to autoantibody creation. In photo-induced PF the loss of intracellular connections is enhanced by autoantibodies and neutrophils with a strong affinity to radiation damaged epidermal tissue [10]. Environmental factors are likely involved in the disease course as well. Pesticides, pharmaceuticals (especially sulfa drugs), hormones, infectious agents, malignancy, radiation (therapeutic radiation), and stress increase risk of developing the disease [11]. Additionally, endemic pemphigus foliaceus appears to have an antigen trigger with an arthropod vector. The prevalence of antibodies against desmoglein-1 is high in people residing in endemic areas of Brazil, but disease onset is preceded by an elevated and sustained antibody response due to an unknown environmental factor.

Genetic factors also play a role in the disease. Haplotypes DRB1*0102 and 0404 carry an increased risk of developing pemphigus foliaceus. There is an increased risk of developing FS in HLA-DRB1 haplotypes, especiallyDRB1*0404, 1402, 1406, and 1401. Drug-induced pemphigus foliaceus can be seen with the use of penicillamine [4], nifedipine, captopril, enalapril and nonsteroidal anti-inflammatory drugs (NSAIDs). Discontinuation of the offending medications results in remission of the condition in 50% of cases.

Worldwide, pemphigus foliaceus is a rare disease. However, there are geographic pockets with much higher incidence rates of the endemic variant of the disease. Areas of Tunisia in North Africa have shown an incidence rate of 6.7 new cases per million each year [5]. Maso Grosso do Sul in Brazil has multiple foci of endemic PF and a prevalence of approximately 3% [6]. Colombia and Peru also some of the other endemic areas [7]. The average age of non-endemic PF ranges from 40 to 60 years of age. Fogo selvagem affects a younger population in the second or third decade of life [8]. Sporadic and endemic PF affect men and women equally. Also, all races and ethnicities are affected about equally.

The mechanism of pemphigus foliaceus involves IgG (mainly the IgG4 subtype) autoantibodies that bind specifically to desmoglein-1 (160 kd), a glycoprotein structural component of desmosomes [9]. These desmosomes are mainly expressed in the granular layer of the epidermis. The mechanism of desmosome destruction and acantholysis induction may involve phosphorylation of intracellular proteins. Complement activation does not play a role in PF.

There is no proven method to prevent pemphigus foliaceus at this time.

Pemphigus is a group of skin diseases that result in the formation of blisters. There are two main types: pemphigus foliaceus (PF) and pemphigus vulgaris. Pemphigus should not be confused with bullous pemphigoid which also results in skin blisters. PF is an autoimmune disorder of the skin and is characterized acantholysis, the loss of cellular adhesions between adjacent keratinocytes in the epidermis. Without the adhesion molecules, layers and sheets of superficial cells split away from each other and form shallow pockets that fill up with fluid and form blisters. These blisters are often very fragile. The superficial skin overlaying the blisters is easily lost, resulting in the formation of shallow erosions.

Endemic pemphigus foliaceus or fogo selvagem (FS) (wild fire in Portuguese) was thought to be only found in the river valleys of rural Brazil. The disease has since been found in other parts including Colombia, El Salvador, Paraguay, and Peru and most recently in Tunisia. Endemic pemphigus foliaceus displays a distinctive epidemiology suggestive of a disorder triggered by an infectious insect-borne agent and immunopathologic findings of pemphigus. The endemic variant also exists in El Bagre and has a similar presentation and histology to Pemphigus erythematosus, also known as Senear-Usher syndrome, but occurs in an endemic fashion [2] [3].

Pemphigus diseases are autoimmune diseases affecting the skin and/or mucous membranes. They are rare outside endemic areas. Environmental and genetic factors are involved with the diseases progression. Pemphigus foliaceus is a relatively benign form of pemphigus that is limited to the skin.

What causes this disease?

Pemphigus foliaceus occurs when the immune system produces autoantibodies that recognize and bind to a specific adhesion molecule (desmosomes) in the skin. These molecules hold the top layers of the skin (epidermis) together. The autoantibodies damage the desmosomes which allow the skin to separate in sheets. Fluid fills these gaps and forms superficial blisters. A normal immune system will not attack the skin. As found in many autoimmune diseases, both environmental and genetic factors may play a role in pathogenesis. Taking medications that contain sulfur can increase the risk of developing this condition. Parasitic infection, especially in the young, can also cause the disease. Other triggers include stress, sunburn, and radiation therapy.

What are the symptoms of pemphigus foliaceus?

The key finding in pemphigus foliaceus is shallow, superficial blisters of the skin. A similar condition, pemphigus vulgaris, involves the skin and the mucous membranes (mouth, eyelids, etc.). Patients with pemphigus foliaceus are usually in good health despite the blisters. The small fluid-filled, superficial blisters usually form on the chest first and then the face and scalp. The blisters rupture very easily because they form in the upper layers of the epidermis and leave behind superficial erosions. These lesions produce a burning, painful sensation and form a scaly crust with a red base. The subtype pemphigus erythematosus only affects the malar portion of the face and may be confused with lupus erythematosus.

How is the condition diagnosis?

Diagnosis requires two biopsies:

• a biopsy of the lesion
• a biopsy adjacent to the lesion (perilesional) in the unaffected skin.

A pathologist will use special stains that may show IgG autoantibodies surrounding the skin cells. Additionally, autoantibodies to desmoglein-1 can be detected in a patient’s serum.

How is pemphigus foliaceus treated?

For focal and minor cases of pemphigus foliaceus, topical corticosteroids are recommended. Widespread and severe cases require systemic corticosteroids and may also require other immunosuppressive combinations. Azathioprine, methotrexate, mycophenolate mofetil, plasma exchange, and rituximab are effective. The combination of nicotinamide 500 mg by mouth three times a day with tetracycline 500 mg by mouth four times a day may also provide relief.

1. Nikolski PV. Materiali K.uchenigu o pemphigus foliaceus [doctoral thesis]. Kiev. 1896.
2. Abreu-Velez AM, Hashimoto T, Bollag WB, et al. A unique form of endemic pemphigus in northern Colombia. J Am Acad Dermatol. 2003 Oct. 49(4):599-608.
3. Abreu-Velez AM, Beutner EH, Montoya F, Bollag WB, Hashimoto T. Analyses of autoantigens in a new form of endemic pemphigus foliaceus in Colombia. J Am Acad Dermatol. 2003 Oct. 49(4):609-14.
4. Brenner S, Ruocco V. D-penicillamine-induced pemphigus foliaceus with autoantibodies to desmoglein-1. J Am Acad Dermatol. 1998 Jul. 39(1):137-8.
5. Bastuji-Garin S, Souissi R, Blum L, et al. Comparative epidemiology of pemphigus in Tunisia and France unusual incidence of pemphigus foliaceus in young Tunisian women. J Invest Dermatol. 1995;104:302–305.
6. Culton DA, Qian Y, Li N, et al. Advances in pemphigus and its endemic pemphigus foliaceus. J Autoimmun. 2008;31:311–324.
7. Abreu-Velez AM, Hashimoto T, Bollag WB, et al. A unique form of endemic pemphigus in northern Colombia. J Am Acad Dermatol. 2003;49:599–608.
8. Meyer N, Misery L. Geoepidemiologic considerations of auto-immune pemphigus. Autoimmun Rev. 2010;9:A379–A382.
9. Ishii K, Amagai M, Komai A, et al. Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus. Arch Dermatol. 1999 Aug. 135(8):943-7.
10. Kikuchi K, Inokuma D, Moriuchi R, Koguchi-Yoshioka H, Yasui C, Shimizu S. Exacerbation of Pemphigus Foliaceus After Electron-beam Radiation. Acta Derm Venereol. 2014 Mar 13.
11. Ruocco V, Ruocco E. Pemphigus and environmental factors. Giornale Dermatol Venereol. 2003. 138:299-309.
12. Colliou N, Picard D, Caillot F, et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med. 2013;5:175ra30.
13. Santoro FA, Stoopler ET, Werth VP; Pemphigus. Dent Clin North Am. 2013 Oct;57(4):597-610. doi: 10.1016/j.cden.2013.06.002. Epub 2013 Aug 12.
14. Mutasim DF, Adams BB. Immunofluorescence in dermatology. J Am Acad Dermatol. 2001;45:803–822.
15. Abasq C, Mouquet H, Gilbert D, et al. ELISA testing of anti-desmoglein 1 and 3 antibodies in the management of pemphigus. Arch Dermatol. 2009;145:529-535.
16. Gurcan HM, Ahmed AR; Efficacy of dapsone in the treatment of pemphigus open link and pemphigoid: analysis of Am J Clin Dermatol. 2009;10(6):383-96.
17. Joly P, Mouquet H, Roujeau JC, et al. A single cycle of rituximab for the treatment of severe pemphigus. N Engl J Med. 2007;357:545-552.