Pemphigus Herpetiformis

Pemphigus Herpetiformis

No Results

No Results

processing….

Pemphigus herpetiformis is a rare autoimmune bullous skin disorder that is considered a clinical variant of pemphigus. Classically, it combines the clinical features of dermatitis herpetiformis with the immunopathologic features of pemphigus. Previously, pemphigus was described using various terms, including herpetiform pemphigus, acantholytic herpetiform dermatitis, pemphigus controlled by sulfapyridine, and mixed bullous disease. Because pemphigus herpetiformis is a clinical variant of pemphigus, it may be more appropriately described with a term that begins with the general group term (pemphigus), followed by a term for the variant subset (herpetiformis), similar to the terms for other pemphigus variants, such as pemphigus vulgaris, pemphigus foliaceus, pemphigus erythematosus, and pemphigus vegetans. [1, 2]

Pemphigus herpetiformis appears to be mediated by the immunoglobulin G (IgG) class of autoantibodies that target the skin epidermis desmoglein components. Most patients demonstrate autoantibodies to desmoglein 1, a desmosomal component predominantly located in the upper epidermis, while a minority of patients demonstrates autoantibodies to desmoglein 3, which is predominantly located in the lower epidermis, and, most recently, desmocollin. [3, 4, 5] The ability of desmoglein 3 to induce an experimental model of pemphigus after transfer of splenocytes from desmoglein 3-immunized desmoglein 3-knockout mice to Rag-2 immunodeficient mice further supports the role of desmogleins as autoantigens. Histologically demonstrated eosinophil and/or neutrophil infiltration into the epidermis may be relevant pathogenically in the disease process of pemphigus herpetiformis. [6]

In the neutrophil-dominant subset, epidermal cells secrete a neutrophil chemokine interleukin 8 (IL-8), which apparently is induced by IgG autoantibodies to desmoglein and may be responsible for the recruitment of neutrophils to the epidermis, resulting in the subsequent blistering process.

Pemphigus herpetiformis appears to be mediated by IgG autoantibodies targeting the interepidermal cell adhesion molecules desmoglein 1 or desmoglein 3. [7, 8, 9] Other less commonly seen target antigens include desmocollin 1, desmocollin 3, and an unidentified 178-kd protein. [10, 11] In many cases, the target antigens are the same as those seen in classic variants of pemphigus. It is likely that antibodies in pemphigus herpetiformis bind to epitopes of desmogleins 1 and 3 and desmocollins 1 and 3, leading to a different clinical presentation. A 2012 study supports this hypothesis through its discovery of a broader epitope distribution in pemphigus herpetiformis than seen in pemphigus vulgaris. [12] However, unlike typical pemphigus vulgaris, significant numbers of inflammatory cells, eosinophils, neutrophils, or mixed eosinophils and neutrophils infiltrate pemphigus herpetiformis lesional skin. The roles of inflammatory cells, particularly eosinophils, in the pathogenesis of pemphigus herpetiformis require further investigation.

Regarding the etiology in the neutrophil-dominant subset of pemphigus herpetiformis, in a study of two patients, IgG autoantibodies that recognized desmoglein 1 (a predominant upper-epidermal protein) exclusively were found to co-localize with expression of interleukin (IL)–8 (a strong neutrophil chemokine) and neutrophilic infiltration at the upper epidermis of the patients’ skin. In the study of two patients, the purified IgG fraction of the patients’ sera induced IL-8 secretion from normal cultured human keratinocytes. Purified IgG from one of these patients also induced the cytoplasmic expression of IL-8 in normal cultured human keratinocytes. Thus, in the neutrophil-dominant subset of pemphigus herpetiformis, it seems that IgG autoantibodies targeting desmoglein 1 were responsible for neutrophil recruitment to the epidermis as a result of inducing epidermal-cell IL-8 expression and secretion. Once at the epidermis, infiltrating neutrophils may result in blisters by releasing their proteases.

In the eosinophil-dominant subset of pemphigus herpetiformis, eosinophilic involvement has not been investigated yet.

One report of a patient with pemphigus herpetiformis has been associated with use of medication (thiopronine). A detailed mechanism is not delineated. [13]

One patient with pemphigus herpetiformis had a history of psoriasis and developed the pemphigus disease shortly after a course of ultraviolet light treatment, raising a possible role of ultraviolet light in the induction of pemphigus herpetiformis. [14]

At least two reported patients with pemphigus herpetiformis had coexisting psoriasis, [15] a chronic inflammatory dermatosis, raising a possible role of “epitope spreading” in the induction of pemphigus herpetiformis. [16]

In one case report, an acute, concurrent eruption of pemphigus herpetiformis and sarcoidosis was described. [17] The temporal and disease severity relationships suggested the two disease processes may share a common link. IL-8, a neutrophil chemotactic factor, has increased activity in both diseases. The pathogenesis of pemphigus herpetiformis includes up-regulation of IL-8 on keratinocytes, causing neutrophil-induced blister formation, while sarcoidosis causes a systemic increase of IL-8 through activation of T helper-2 cells during granuloma formation. Additionally, phosphorylation of p28 leads to an intracellular signaling cascade involved in both inflammatory diseases as well as psoriasis.

Pemphigus herpetiformis may also demonstrate autoantibodies targeting antigen (or antigens) other than the typical desmoglein proteins (desmoglein 1 or 3). [18]

A patient with pemphigus herpetiformis, manifested by prominent skin involvement with no oral mucosal involvement, demonstrated autoantibodies to desmoglein 3, in contrast with what would typically be seen with this antibody. [19]

Pemphigus herpetiformis may also present with lesions characteristic of the inflammatory stage of heritable pretibial dystrophic epidermolysis bullosa. [20]

Pemphigus herpetiformis is a rare clinical variant of pemphigus. Frequency of occurrence remains undetermined. Although frequency of occurrence of pemphigus herpetiformis is not determined, pemphigus herpetiformis has been reported in Europe, Japan, and the United States. In a large study conducted in Eastern Europe, 15 patients (7.3%) with pemphigus herpetiformis were found among 205 patients with pemphigus. In a smaller study conducted in Italy, 5 patients with pemphigus herpetiformis were found among 84 patients with pemphigus. Therefore, pemphigus herpetiformis accounts for approximately 6-7% of pemphigus in European populations.

Because pemphigus herpetiformis is rare, ethnic distribution is not determined yet. Because pemphigus herpetiformis occurs in the United States, Europe, and Asia, it does not appear to have a specific ethnic predominance.

Because pemphigus herpetiformis is rare, sex distribution has yet to be defined clearly. Studies in the literature do not appear to support a sex predilection.

The age of onset for pemphigus herpetiformis ranges from 30-80 years, with a mean age of onset of 60 years. Moutran et al describes an unusual case of onset at age 6 years successfully treated with dapsone. [21] One case report describes transplacental transmission of pemphigus herpetiformis to an otherwise healthy infant with subsequent resolution after age 3 weeks. [22]

The prognosis for pemphigus herpetiformis usually is excellent. Pemphigus herpetiformis is not associated with significant mortality; however, pemphigus herpetiformis is associated with significant pruritus. Treatment regimens for pemphigus herpetiformis may cause significant adverse effects that must be monitored closely by the patient’s physicians. Severe pruritus is noted in approximately one half of patients affected with pemphigus herpetiformis. At least 2 cases of pemphigus herpetiformis have been reported to occur in association with lung cancer. Whether this association was coincidental is not clear. [23, 24] In addition, pemphigus herpetiformis has been associated with prostate cancer development in one case. [25]

Joly P, Litrowski N. Pemphigus group (vulgaris, vegetans, foliaceus, herpetiformis, brasiliensis). Clin Dermatol. 2011 Jul-Aug. 29(4):432-6. [Medline].

Laws PM, Heelan K, Al-Mohammedi F, Walsh S, Shear NH. Pemphigus herpetiformis: a case series and review of the literature. Int J Dermatol. 2015 Sep. 54 (9):1014-22. [Medline].

Kasperkiewicz M, Kowalewski C, Jablonska S. Pemphigus herpetiformis: from first description until now. J Am Acad Dermatol. 2014 Apr. 70(4):780-7. [Medline].

On HR, Hashimoto T, Kim SC. Pemphigus herpetiformis with IgG autoantibodies to desmoglein 1 and desmocollin 1. Br J Dermatol. 2014 Sep 21. [Medline].

Hong WJ, Hashimoto T, Kim SC. A Case of Pemphigus Herpetiformis with Only Immunoglobulin G Anti-Desmocollin 3 Antibodies. Ann Dermatol. 2016 Feb. 28 (1):102-6. [Medline].

Amagai M, Tsunoda K, Suzuki H, Nishifuji K, Koyasu S, Nishikawa T. Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus. J Clin Invest. 2000 Mar. 105(5):625-31. [Medline]. [Full Text].

Brod C, Fierlbeck G, Metzler G, Sonnichsen K, Rocken M, Schaller M. [Desmoglein 1-negative, desmoglein 3-positive pemphigus herpetiformis with involvement of oral mucous membranes]. J Dtsch Dermatol Ges. 2005 Apr. 3(4):280-2. [Medline].

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. [Medline].

Kubo A, Amagai M, Hashimoto T, et al. Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmoglein 3). Br J Dermatol. 1997 Jul. 137(1):109-13. [Medline].

Tateishi C, Tsuruta D, Nakanishi T, Uehara S, Kobayashi H, Ishii M, et al. Antidesmocollin-1 antibody-positive, antidesmoglein antibody-negative pemphigus herpetiformis. J Am Acad Dermatol. 2010 Jul. 63 (1):e8-10. [Medline].

Prado R, Brice SL, Fukuda S, Hashimoto T, Fujita M. Paraneoplastic pemphigus herpetiformis with IgG antibodies to desmoglein 3 and without mucosal lesions. Arch Dermatol. 2011 Jan. 147 (1):67-71. [Medline].

Ohyama B, Nishifuji K, Chan PT, Kawaguchi A, Yamashita T, Ishii N, et al. Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2-based swapped molecules. J Invest Dermatol. 2012 Apr. 132 (4):1158-68. [Medline].

Verdier-Sevrain S, Joly P, Thomine E, et al. Thiopronine-induced herpetiform pemphigus: report of a case studied by immunoelectron microscopy and immunoblot analysis. Br J Dermatol. 1994 Feb. 130(2):238-40. [Medline].

Sanchez-Palacios C, Chan LS. Development of pemphigus herpetiformis in a patient with psoriasis receiving UV-light treatment. J Cutan Pathol. 2004 Apr. 31(4):346-9. [Medline].

Morita E, Amagai M, Tanaka T, Horiuchi K, Yamamoto S. A case of herpetiform pemphigus coexisting with psoriasis vulgaris. Br J Dermatol. 1999 Oct. 141(4):754-5. [Medline].

Chan LS, Vanderlugt CJ, Hashimoto T, et al. Epitope spreading: lessons from autoimmune skin diseases. J Invest Dermatol. 1998 Feb. 110(2):103-9. [Medline].

Mangold AR, Costello CM, Pittelkow MR, DiCaudo DJ. Concomitant pemphigus herpetiformis and sarcoidosis. JAAD Case Rep. 2016 Nov. 2 (6):436-438. [Medline].

Miura T, Kawakami Y, Oyama N, et al. A case of pemphigus herpetiformis with absence of antibodies to desmogleins 1 and 3. J Eur Acad Dermatol Venereol. 2010 Jan. 24(1):101-3. [Medline].

Lebeau S, Muller R, Masouye I, Hertl M, Borradori L. Pemphigus herpetiformis: analysis of the autoantibody profile during the disease course with changes in the clinical phenotype. Clin Exp Dermatol. 2009 Oct 23. [Medline].

Montgomery JR, Chan LS. An unusual clinical presentation of pemphigus herpetiformis with marked response to dapsone. J Am Acad Dermatol. 2010. In press.

Moutran R, Maatouk I, Stephan F, Halaby E, Abadjian G, Tomb R. Letter: Pemphigus herpetiformis of age of onset at 6 years. Dermatol Online J. 2011 Jun 15. 17(6):10. [Medline].

Schoch JJ, Boull CL, Camilleri MJ, Tollefson MM, Hook KP, Polcari IC. Transplacental Transmission of Pemphigus Herpetiformis in the Setting of Maternal Lymphoma. Pediatr Dermatol. 2015 Nov-Dec. 32 (6):e234-7. [Medline].

Kubota Y, Yoshino Y, Mizoguchi M. A case of herpetiform pemphigus associated with lung cancer. J Dermatol. 1994 Aug. 21(8):609-11. [Medline].

Palleschi GM, Giomi B. Herpetiformis pemphigus and lung carcinoma: a case of paraneoplastic pemphigus. Acta Derm Venereol. 2002. 82(4):304-5. [Medline].

Marzano AV, Tourlaki A, Cozzani E, Gianotti R, Caputo R. Pemphigus herpetiformis associated with prostate cancer. J Eur Acad Dermatol Venereol. 2007 May. 21(5):696-8. [Medline].

Ohata C, Koga H, Teye K, Ishii N, Hamada T, Dainichi T, et al. Concurrence of bullous pemphigoid and herpetiform pemphigus with IgG antibodies to desmogleins 1/3 and desmocollins 1-3. Br J Dermatol. 2012 Aug 27. [Medline].

Huang C, Wu Y, Kao C. Localized pemphigus herpetiformis: two case reports. Dermatologica Sinica. 2010 Mar. 28 (1):36-39.

Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus variants. J Am Acad Dermatol. 1999 May. 40 (5 Pt 1):649-71;672-3. [Medline].

Jablonska S, Chorzelski TP, Beutner EH, Chorzelska J. Herpetiform pemphigus, a variable pattern of pemphigus. Int J Dermatol. 1975 Jun. 14 (5):353-9. [Medline].

Cunha PR, Jiao D, Bystryn JC. Simultaneous occurrence of herpetiform pemphigus and endemic pemphigus foliaceus (fogo selvagem). Int J Dermatol. 1997 Nov. 36 (11):850-4. [Medline].

Faria PCP, Cruz CC, Abulafia LA, Maceira JMP, Cassia FF, Medeiros PM. The importance of direct immunofluorescence in pemphigus herpetiformis diagnosis. An Bras Dermatol. 2017. 92 (5 Suppl 1):145-147. [Medline].

Hashimoto T, Ogawa MM, Konohana A, Nishikawa T. Detection of pemphigus vulgaris and pemphigus foliaceus antigens by immunoblot analysis using different antigen sources. J Invest Dermatol. 1990 Mar. 94(3):327-31. [Medline].

Ishii K, Amagai M, Hall RP, et al. Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J Immunol. 1997 Aug 15. 159(4):2010-7. [Medline].

Wozel G, Blasum C. Dapsone in dermatology and beyond. Arch Dermatol Res. 2014 Mar. 306 (2):103-24. [Medline].

Hofmann SC, Juratli HA, Eming R. Bullous autoimmune dermatoses. J Dtsch Dermatol Ges. 2018 Nov. 16 (11):1339-1358. [Medline].

Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006 Oct 26. 355(17):1772-9. [Medline].

American College of Rheumatology. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. American College of Rheumatology Task Force on Osteoporosis Guidelines. Arthritis Rheum. 1996 Nov. 39(11):1791-801. [Medline].

Blanca Anais Estupiñan University of Central Florida College of Medicine

Blanca Anais Estupiñan is a member of the following medical societies: American College of Physicians, American Medical Association, American Psychiatric Association

Disclosure: Nothing to disclose.

Neil Sandhu, MD, FAAD Dermatologist (Medical/Cosmetics) and Mohs Surgeon, Gulf Coast Dermatology

Neil Sandhu, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Lawrence S Chan, MD Dr Orville J Stone Professor of Dermatology, Head, Department of Dermatology, University of Illinois College of Medicine

Lawrence S Chan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Dermatological Association, American Medical Association, Association of Professors of Dermatology, Chicago Dermatological Society, Dermatology Foundation, Illinois State Medical Society, Microcirculatory Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Smeena Khan, MD Private Practice, Adult and Pediatric Dermatology Associates

Smeena Khan, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Pemphigus Herpetiformis

Research & References of Pemphigus Herpetiformis|A&C Accounting And Tax Services
Source