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Benign Familial Pemphigus

Hailey-Hailey Disease

Benign familial pemphigus, also known as Hailey-Hailey disease, is a rare familial blistering skin disorder characterized by recurring skin lesions in intertriginous areas that are exacerbated by heat, sweating, and friction. The diagnosis rests on clinical criteria, a positive family history and typical findings on histopathological examination, while immunofluorescence, typically used for this group of disorders, is negative.


Presentation

Familial benign pemphigus, initially described in Hailey brothers in the 1930s (hence the term Hailey-Hailey disease), is a rare blistering skin disease caused by mutations in the ATP2C1 gene coding for cellular electrolyte transporters that are essential in maintaining cell-to-cell adhesion [1] [2] [3]. The autosomal dominant pattern of inheritance is the reason why family history is the most important risk factor for its development [4] [5] [6] [7]. The onset of symptoms is typically observed during the second, third, and fourth decades of life, although patients of all ages have been reported in the literature [4] [5]. The hallmark of familial benign pemphigus is the recurrent appearance of vesicles, erosions, and plaques in intertriginous areas (in a symmetrical fashion) - the groins, submammary regions, the axillae, and the neck [1] [4] [5] [6] [7]. Skin lesions are painful, often pruritic, and have a foul smell [1]. Furthermore, heat, excessive sweating, friction, trauma, stress, and constrictive clothes have been shown to aggravate symptoms [1] [4] [5] [6]. Nail fragility is an important non-cutaneous finding in these patients [4] [5]. Although the clinical course varies from patient to patient, the lesions heal spontaneously without therapy and recur several times throughout the patient's life [1] [8]. Unfortunately, some patients may experience a significant impairment of their quality of life due to familial benign pemphigus [8].

Localized Pain
  • Tolerance was overall acceptable with local pain during and shortly after irradiation being the main limiting factor.[ncbi.nlm.nih.gov]
Turkish
Heat Intolerance
  • intolerance): 3 people, 50.00% Nausea (feeling of having an urge to vomit): 3 people, 50.00% Appetite - Increased (increased appetite is when you want to eat much more often or in larger quantities than your body requires): 3 people, 50.00% Diarrhea:[ehealthme.com]
Severe Pain
  • However, the patient was dissatisfied due to protracted healing time, development of contractures, and severe pain.[medicaljournals.se]
Increased Appetite
  • appetite is when you want to eat much more often or in larger quantities than your body requires): 3 people, 50.00% Diarrhea: 3 people, 50.00% Fungal Infection: 3 people, 50.00% Insomnia (sleeplessness): 3 people, 50.00% Abnormal Dreams: 3 people, 50.00%[ehealthme.com]
Blister
  • Benign familial pemphigus, also known as Hailey-Hailey disease, is a rare familial blistering skin disorder characterized by recurring skin lesions in intertriginous areas that are exacerbated by heat, sweating, and friction.[symptoma.com]
  • These are crusty blisters that tend to form on your chest, back, and shoulders. They don’t hurt, but they do itch. How is Pemphigus Diagnosed? It can be tricky. That’s because a number of conditions can cause blisters.[webmd.com]
  • Blisters can accompany some types of skin rashes and inflammatory conditions, including certain autoimmune diseases. Depending upon the cause of the blisters, blisters may occur singly or in groups.[medicinenet.com]
  • The painful blisters break and sometimes become infected and raw, with new blisters forming over raw skin in a sometimes seemingly unending cycle of outbreaks.[en.wikipedia.org]
  • Some patients are more severely affected and experience more persistent painful raw areas of the skin with development of superficial blisters. Hailey-Hailey disease - printable version[bad.org.uk]
Leukonychia
  • Electron beam radiotherapy Dermabrasion Glycopyrrolate Afamelanotide Clinical images Images hosted on other servers: Hailey-Hailey in right axilla Hyperpigmented plaques over groin Hailey-Hailey lesions on left groin Figure 2b: Showing longitudinal leukonychia[pathologyoutlines.com]
  • Patients with Hailey-Hailey disease may also have nail manifestation called ‘longitudinal leukonychia’ which are longitudinal white bands on the fingernails.[aocd.org]
  • In patients with limited or atypical disease, longitudinal leukonychia may serve as a diagnostic clue.[therapeutique-dermatologique.org]
  • Longitudinal leukonychia, seen 71% in one study, may help in the diagnosis of HHD. [6] However, this nail finding was not observed in the reported case.[e-ijd.org]
Decreased Sweating
  • The proposed use of botulinum toxin is due to its action blocking cholinergic stimulation by the postganglionic sympathetic fibers, decreasing sweat production by the sweat glands. [3], [9], [10] Heat and sweat are exacerbating factors in patients with[ijdd.in]

Workup

The diagnosis of familial benign pemphigus can only be made with a detailed patient history and a meticulous physical examination that provides sufficient data for clinical suspicion of this rare blistering skin disorder. In addition to the assessment of the course and progression of symptoms, patients must be asked about the familial presence of symptoms, which may be the crucial detail in narrowing the differential diagnosis. On the other hand, observing typical cutaneous findings in intertriginous areas and associated symptoms can be quite helpful. One of the key features of familial benign pemphigus is the absence of antibody deposition on immunofluorescence testing [4] [5], the principal method for assessing and stratifying other blistering skin lesions (Pemphigus, Pemphigoid, etc.). For this reason, a histopathological examination of lesions is critical. Generalized suprabasal loss of cellular adhesions (known as acantholysis), resembling a dilapidated brick wall appearance, is the hallmark of familial benign pemphigus [4] [8]. Other notable findings on histology are dyskeratosis and preservation of the dermis [5] [8]. Thus, a combination of clinical criteria, a positive family history, and microscopic examination of the skin comprise the diagnostic workup of this rare, but potentially debilitating skin blistering disease.

Treatment

  • INTRODUCTION/BACKGROUND: Treatment of benign familial pemphigus or Hailey-Hailey disease (HHD), a rare inherited condition associated with a significant impairment of quality of life, is often challenging and disappointing with frequent relapses and infectious[ncbi.nlm.nih.gov]
  • Systemic treatments Systemic treatments are often used when lesions are refractory to local topical treatments or when the disease is too diffuse to be treated focally ( Table 2 ).[dovepress.com]
  • Treatment is symptomatic with general measures to prevent friction and Sweat.[ijdd.in]
  • Topical medical treatment can alleviate the symptoms in milder forms. Physical treatments are very effective for more severe forms: CO2 laser therapy (pulse or continuous) is often proposed as a first-line treatment.[orpha.net]
  • Local treatments may improve inflammation but do not treat the underlying cause, targeted systemic therapies exist but there is little evidence supporting their use, physical treatments are cumbersome.[pemphigus.org]

Prognosis

  • […] painful blisters and rashes to form on the skin, often in the skin folds The cause of Hailey-Hailey Disease is a genetic defect and the condition is inherited in an autosomal dominant manner A treatment of the condition involves steroid therapy; the prognosis[dovemed.com]
  • A distinct type of cutaneous B-cell lymphoma with an intermediate prognosis. Dutch Cutaneous Lymphoma Working Group. Arch Dermatol 1996; 132:1304-1308. ‏ الصفحة 267 - Fletcher V, Sagebiel RW.[books.google.com]
  • Hailey-Hailey disease: the clinical features, response to treatment and prognosis. Br J Dermatol. 1992;126:275-82. [ Links ] 3 Riahi RR, Yamazaki ML, Kelly BC. Tzanck smear utilized in the diagnosis of Hailey-Hailey disease mimicking genital herpes.[scielo.br]
  • […] disseminated herpes simplex infection of pre-existing skin disease) is a rare complication, requiring systemic antiviral treatment. [ 12 ] A single case report describes squamous cell carcinoma developing in a vulval lesion after tacrolimus treatment. [ 13 ] Prognosis[patient.info]

Etiology

  • Etiology Mutations in the ATP2C1 gene (localised to 3q21-q24), encoding a calcium pump, cause the disease by impairing epidermal keratinocyte adhesion.[orpha.net]
  • Qualifiers English : BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology EH ethnology ET etiology[decs.bvs.br]
  • (Etiology) Hailey-Hailey Disease is an autosomal dominant genetic condition It is caused by missing one of the two copies of the ATP2C1 gene on chromosome 3, which encodes the protein hSPCA1 Approximately 30% of the cases, are caused by random mutations[dovemed.com]
  • […] which are calcium dependent adherence proteins (cadherins) ( Indian Dermatol Online J 2016;7:147 ) Hailey-Hailey and Darier disease share similar pathogenesis, as opposed to pemphigus vulgaris, in which autoantibodies develop against desmosomal proteins Etiology[pathologyoutlines.com]

Epidemiology

  • Summary Epidemiology Prevalence is unknown. Clinical description Skin lesions appear during adolescence or more often at the age of 30-40 years; they are relapsing and recurrent. Lesions can be complicated by heat, rubbing or superinfections.[orpha.net]
  • Note English : 92 Allowable Qualifiers English : BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology[decs.bvs.br]
  • Synonyms: familial benign chronic pemphigus, Hailey-Hailey disease Epidemiology and aetiology This is a rare inherited autosomal dominant skin disorder, caused by a genetic mutation in the ATP2C1 gene located on chromosome 3. [ 1 ] Occasionally sporadic[patient.info]
  • Epidemiology Frequency No precise data are available on the incidence of familial benign pemphigus. Sex Both sexes are affected equally by familial benign pemphigus.[emedicine.medscape.com]
Sex distribution
Age distribution

Pathophysiology

  • […] topical antimicrobials Terminology Also called benign familial pemphigus Papular acantholytic dermatosis in genitocrural region may be a localized form of H-H disease Sites Axillae, groin, perianal and inframammary areas Rarely involves other sites Pathophysiology[pathologyoutlines.com]
  • Pathophysiology The exact role that these mutations play in the clinical manifestation of Hailey-Hailey disease are not yet clear.[dermatologyadvisor.com]
  • Pathophysiology Keratinocytes are held together through desmosomes and adherens junctions. These junctions consist of calcium-binding transmembrane glycoproteins, which contribute to cellular adhesion.[emedicine.medscape.com]

Prevention

  • Trying to prevent bacterial, viral, and fungal infections in the affected areas is also important, and drugs used to treat or prevent these infections are commonly used.[medicinenet.com]
  • Prevention and treatment of bacterial, viral and fungal infections is also important, and drugs used to treat these infections are commonly used.[therapeutique-dermatologique.org]
  • Management and treatment There is no specific treatment, but drying the affected areas is essential as well as employing measures to prevent bacterial, fungal and viral infections.[orpha.net]
  • Intracutaneous injections of botulinum toxin to inhibit perspiration may be of benefit. [9] Maintaining a healthy weight, avoiding heat and friction of affected areas, and keeping the area clean and dry may help prevent flares.[en.wikipedia.org]
  • Hailey-Hailey Disease is a complex disease believed to involve both, one's genetic predisposition and certain environmental factors Currently, there are no definitive methods to prevent Hailey-Hailey Disease What is the Prognosis of Hailey-Hailey Disease[dovemed.com]

References

Article

  1. Hunt R, O'Reilly K, Ralston J, Kamino H, Shupack JL. Familial benign chronic pemphigus (Hailey-Hailey disease). Dermatol Online J. 2010;16(11):14.
  2. Durr G, et al. The medial-Golgi ion pump Pmr1 supplies the yeast secretory pathway with Ca2+ and Mn2+ required for glycosylation, sorting, and endoplasmic reticulum-associated protein degradation. Mol Biol Cell. 1998;9:1149.
  3. Hakuno M, et al. Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease. Br J Dermatol. 2000;142:702.
  4. Warycha M, Patel R, Meehan S, et al; Familial benign chronic pemphigus (Hailey-Hailey disease). Dermatol Online J. 2009;15(8):15.
  5. Tchernev G, Cardoso JC. Familial benign chronic pemphigus (Hailey-Hailey Disease): use of topical immunomodulators as a modern treatment option. Rev Med Chil. 2011;139(5):633-637.
  6. Graham PM, Melkonian A, Fivenson D. Familial benign chronic pemphigus (Hailey-Hailey disease) treated with electron beam radiation. JAAD Case Rep. 2016;2(2):159-161.
  7. Gisondi P, Sampogna F, Annessi G, Girolomoni G, Abeni D. Severe impairment of quality of life in Hailey-Hailey disease. Acta Derm Venereol. 2005;85(2):132-135.
  8. Arora H, Bray FN, Cervantes J, Falto Aizpurua LA. Management of familial benign chronic pemphigus. Clin Cosmet Investig Dermatol. 2016;9:281-290.

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Last updated: 2019-07-11 20:32