PHYSICALLY INDUCED PEMPHIGUS AFTER COSMETIC PROCEDURES

Background. Pemphigus is a vesiculobullous autoimmune disease characterized by acantholysis due to antibodies against epidermal antigens. Case Reports. We report the first two cases of pemphigus in which lesions appeared in areas traumatized by cosmetic procedures. In one case, the patient had a history of pemphigus under excellent control; pemphigus lesions appeared only in her surgical scars 2 months after a reduction mammoplasty and facelift. The other patient presented with an outbreak of pemphigus 4 weeks after a chemical peel. Conclusions. Physical agents including infrared and ionizing radiation as well as ultraviolet light are known triggers of pemphigus. We suggest that cosmetic procedures can initiate pemphigus and that this change must be differentiated from postoperative wound infections and other reasons for poor wound healing.     

Paraneoplastic pemphigus with circulating antibodies directed exclusively against the pemphigus vulgaris antigen desmoglein 3

A patient with follicular B-cell lymphoma presented with erythroderma associated with cutaneous and mucosal blisters. Histologic and direct immunofluorescence analysis of lesional skin showed a typical pattern of paraneoplastic pemphigus (PNP). Interestingly, indirect immunofluorescence on rat bladder was negative and immunoblot analysis of the patient's serum on epidermal extracts demonstrated antiepidermal antibodies that only recognized the pemphigus vulgaris antigen desmoglein 3, with no antibodies directed against the different proteins of the plakin family. To our knowledge this has never been reported in the literature. It exemplifies the overlap between pemphigus vulgaris and PNP and the pathogenic role of anti-desmoglein 3 antibodies in PNP. Moreover, it underscores the need to consider clinical, histologic, and immunologic features for the diagnosis of PNP.     

Induction of pemphigus by X-ray irradiation

A 70–year-old female who had been suffering from psoriasis vulgaris for 20 years, and from lymphoma for 5 years, developed a vesiculo-bullous eruption two weeks after exposure to radiotherapy. The historical and immunofluorescent findings confirmed the clinical diagnosis of pemphigus vulgaris. Immunological tests revealed impaired cell-mediated immunity. It is suggested that the X-ray irradiation may have served as a provoking factor for the development of the pemphigus in a patient with underlying immunological disturbances.     

Graft-versus-host disease-like immunophenotype and apoptotic keratinocyte death in paraneoplastic pemphigus

Paraneoplastic pemphigus (PP) is an autoimmune disease, which is frequently associated with non-Hodgkin's lymphoma. Autoantibodies against components of the cytoplasmic plaque of epithelial desmosomes are usually present in the sera and are believed to play a major pathogenic part in acantholysis and suprabasal epidermal blistering. However, another typical histological feature of PP, interface dermatitis with keratinocyte dyskeratosis, is shared with skin diseases that involve epithelial damage mediated by T cells. Here, we present the detailed characterization of the cutaneous T-cell response in a patient with PP and demonstrate a selective epidermal accumulation of activated CD8+ T cells together with an increased local production of interferon-gamma and tumour necrosis factor-alpha, and a strong expression of HLA-DR and ICAM-1 on keratinocytes. Apoptosis was identified as a key mechanism of keratinocyte death, and appeared independent of the FAS/FAS ligand (FAS-L) pathway, as epidermal expression of FAS was not increased compared with normal skin, and FAS-L was undetectable on the protein and mRNA level. Triple therapy with high-dose corticosteroids, cyclophosphamide and intravenous immunoglobulins reduced levels of pemphigus-like autoantibodies and reversed the cutaneous inflammatory reaction leading to long-standing clinical remission. Our findings support the concept of a major contribution of cytotoxic T lymphocytes to the immunopathology of paraneoplastic pemphigus.     

Therapy of paraneoplastic pemphigus with Rituximab: a case report and review of literature

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease with poor prognosis when associated with malignant neoplasm. We report the case of a patient with PNP associated with a CD20+ non-Hodgkin follicular lymphoma who was treated with Rituximab plus corticosteroids and short courses of cyclosporin. One and a half years after Rituximab therapy, oral ulcerations had cleared and oral methylprednisolone was slowly tapered down without further recurrences. In the course of the disease, the patient developed sepsis due to Listeria monocytogenes and viral infections by human herpes virus 1 and 3. At the end-stage of the disease she developed a cutaneous infection from Mycobacterium chelonae. The patient died 2 years and 7 months after the onset of PNP. Rituximab may be useful for PNP therapy, but further studies are necessary to confirm this hypothesis.     

D-penicillamine-induced pemphigus, polymyositis and myasthenia]

BACKGROUND: D-penicillamine can induce autoimmune disease, particularly in patients with associated immune disorders. CASE REPORT: A 67-year old woman who had been taking D-penicillamine for 15 months for rheumatoid arthritis was hospitalized due to the development of a bullous eruption and proximal muscle deficiency. Search for intercellular antisubstance antibodies in serum was negative. The skin biopsy histology revealed intra-epidermal cleavage in the mucosal body and direct immunofluorescence revealed epidermal frame-marking with anti-IgG and anti-C3 antibodies. Other tests revealed muscular cytolysis, and anti-acetylcholine receptor antibodies. The electromyogram showed neuromuscular block without muscle deficiency and muscle biopsy showed moderate myositis. D-penicillamine was interrupted and was followed by cure of the pemphigus and aggravation of the myositis, requiring high-dose systemic corticosteroid therapy. DISCUSSION: This patient developed D-penicillamine induced pemphigus, a rather frequent observation. The desmoglein immunolabelling favored drug-induced pemphigus and the course was rapidly favorable after withdrawal. Pemphigus had developed simultaneously with signs of myasthenia and polymyositis. Polymyositis and myasthenia are also known complications of D-penicillamine therapy. The association of these three complications suggests that D-penicillamine can unmask certain antigens or have an immunomodulator effect.     

Oral pemphigus vulgaris after anthrax vaccine administration: association or coincidence?

Pemphigus vulgaris is an autoimmune blistering disorder of the skin and mucous membranes. Numerous medications, ultraviolet light, and radiation have all been implicated in the etiology of the disease. We present a patient with pemphigus vulgaris whose disease developed after administration of anthrax vaccine. The histologic and immunofluorescence findings were characteristic of pemphigus vulgaris. Adverse systemic events associated with the anthrax vaccine consist primarily of flu-like symptoms. Previous cases of pemphigus vulgaris associated with anthrax vaccine administration have not been reported. Considering the recent deliberate outbreaks of anthrax and continued threats of bioterrorism, the potential exists for widespread administration of the anthrax vaccine. Accordingly, continued observation and documentation of true adverse events is needed.     

Paraneoplastic pemphigus associated with non-Hodgkin B-cell lymphoma and good response to prednisone

Paraneoplastic pemphigus is a life-threatening autoimmune bullous disease associated with neoplasia, generally of lymphoid origin. Immunosuppressive therapy is often disappointing and there are only a few reports of patients surviving more than 2 years. These cases were generally associated with benign neoplasms. We report here the case of a patient with paraneoplastic pemphigus associated with non-Hodgkin B-cell lymphoma who had a surprisingly good response to systemic corticosteroids and remains free of lesions more than 3 years later despite progression of her neoplasm.     

Histopathologic features seen with radiation recall or enhancement eruptions

Background: Although a radiation recall or enhancement eruption has been associated with a number of chemotherapeutic drugs, the histologic features have rarely been described. Objective: Our goal was to define the histologic features of radiation recall and enhancement eruptions in order to better understand their pathogenesis. Methods: We present ten patients on chemotherapeutic agents who developed erythematous maculopapular to psoriasiform eruptions often with associated follicular pustules. These eruptions occurred at the sites of prior or concurrent radiation therapy. Results: The most common class of drugs inducing these reactions were antibiotic chemotherapeutic agents alone or in combination with other chemotherapeutic drugs. In addition to routine histology, in four patients immunohistochemical staining for p53 was performed at the sites of the eruptions after resolution and at noninvolved sites matched for ultraviolet radiation (UVR) exposure. Histologic features in patients receiving concurrent radiation therapy included epidermal dysplasia, keratinocytes showing features of necrosis, increased mitotic figures, and a mixed inflammatory infiltrate. At sites of prior radiation therapy, the biopsy specimens showed a similar spectrum of epidermal changes and, in some cases, psoriasiform dermatitis with clearing within cells in the upper layers of the epidermis. Additional dermal changes included dermal fibrosis, vasodilatation, and atypical fibroblasts. Moderate to marked solar elastosis was seen in the majority of biopsy specimens. Immunohistochemical studies after resolution showed only a modest increase in p53 staining in epidermal keratinocytes in 3 of 4 sites of recall and enhancement eruptions after resolution of the reactions compared to skin that was matched for similar UVR exposure. Conclusion: Cumulative direct DNA damage and oxidative stress are probably important in radiation recall and enhancement eruptions, and these changes may be modulated by underlying nutritional deficits. Cumulative p53 mutations may play some role but are probably not a major factor in these eruptions. Mitochondrial dysfunction, which is known to occur with prior and concurrent radiation and chemotherapy, may be important in these eruptions. In addition to improvements in general nutrition, topical or oral antioxidant therapy may be a potential therapy to avoid radiation enhancement and recall reactions     

Transient acanthosis-nigricans-like dermatosis in re-epithelializing lesions of pemphigus foliaceus.

A patient is described who developed hyperkeratotic, hyperpigmented plaques, similar to acanthosis nigricans in re-epithelializing erosions of pemphigus foliaceus. The lesions regressed completely after a few months. This phenomenon can be attributed to a K?bner phenomenon after epidermal damage or can be a result of systemic corticosteroid therapy.     

Radiotherapy-induced pemphigus vulgaris with autoantibodies targeting a 110 kDa epidermal antigen

Background Pemphigus is an autoimmune intraepidermal blistering disease mediated by autoantibodies targeting desmosomes. It can be induced by many triggers, such as ionizing radiation. Methods We report a case of radiotherapy‐induced pemphigus (RIP) with a review of the published cases in the English and French literature. Results A 61‐year old man was diagnosed to have epidermoid carcinoma of the piriform sinus and then received a 70 Gy radiation therapy. One month after the treatment completion, multiple blisters and erosions occurred initially on the site of irradiation, then in other skin areas. Histological examination showed an intraepidermal blister with acantholysis and necrosis of individual keratinocytes. Direct immunofluorescence and indirect immunofluorescence were typical of pemphigus. Immunoblot revealed antibodies reacting with a 110 kDa antigen. This feature was consistent with the diagnosis of RIP. Less than 20 cases of RIP have been reported previously. Mean age at diagnosis was 64.2 years, and there is a slight female preponderance. RIP occurred, in most cases, initially within the area of irradiation. Conclusion Our patient showed some distinctive findings never reported previously in RIP: a histological focal keratinocyte necrosis, and the presence of autoantibodies reacting with a 110 kDa keratinocytic protein in immunoblot analysis. Because of a different prognosis, it is important to differentiate RIP and paraneoplastic pemphigus (PNP), although cases of ionizing radiation‐induced PNP had also been described. As in our patient, RIP seems to respond well to systemic corticosteroids and immunosuppressive therapy, which induce remission within a few months.     

Drug-induced pemphigus: autoantibodies directed against the pemphigus antigen complexes are present in penicillamine and captopril-induced pemphigus

Pemphigus is an autoimmune blistering disease characterized by circulating autoantibodies directed against the keratinocyte cell surface. The two variants, pemphigus foliaceus and pemphigus vulgaris, can be distinguished at the molecular level by immunochemical studies. The large majority of patients with pemphigus develop the disease spontaneously; however, there is a small group of patients who develop pemphigus after treatment with certain medications, of which penicillamine and captopril are the best documented. Most patients with drug-induced pemphigus have circulating and/or tissue bound epidermal cell surface autoantibodies; however, the molecular specificity of these autoantibodies has not been studied. We performed immunoprecipitation studies utilizing extracts of 125I-labeled suction blister epidermis and the sera of three patients with drug-induced pemphigus foliaceus (two due to penicillamine and one due to captopril) and one patient with captopril-induced pemphigus vulgaris. We found that the three patients with drug-induced pemphigus foliaceus had circulating autoantibodies that are directed against the pemphigus foliaceus antigen complex and that the one patient with drug-induced pemphigus vulgaris had circulating autoantibodies that are directed against the pemphigus vulgaris antigen complex. This study demonstrates that autoantibodies from drug-induced pemphigus patients have the same antigenic specificity, on a molecular level, as do autoantibodies from other pemphigus patients.     

Immunoglobulin A pemphigus associated with immunoglobulin A gammopathy and lung cancer

Immunoglobulin (Ig)A pemphigus is a rare disease marked by a vesiculopustular eruption characterized by intercellular IgA deposition in the epidermis. It has clinical and histopathological heterogeneity and encompasses two subgroups: subcorneal pustular dermatosis type and intraepidermal neutrophilic IgA dermatosis type. IgA pemphigus has been rarely associated with monoclonal IgA paraprotein, myeloma and B-cell lymphoma in the past. We report the first case, to our knowledge, of a 47-year-old male patient with a subcorneal pustular dermatosis type of IgA pemphigus associated with IgA gammopathy and lung cancer.     

The diagnostic use of monoclonal antibodies in a variety of dermatologic conditions

Monoclonal antibodies have been used to characterize subpopulations of lymphocytes in a variety of dermatologic conditions by immunofluorescence and immunoperoxidase staining. Various clinical presentations of cutaneous T-cell lymphoma have been shown to be neoplastic expansions of helper T-lymphocytes. Immunoperoxidase studies using subset-specific monoclonal antibodies have allowed the differentiation of patients with cutaneous T-cell lymphoma from lymphocytoma cutis and B-cell lymphomas secondarily involving the epidermis. Increased numbers of OKT-6 positive Langerhans' cells in the dermal infiltrates of patients with cutaneous T-cell lymphoma may be another immunocytological marker of this disease. Studies done on circulating lymphocytes of patients with psoriasis and pemphigus vulgaris have shown normal ratios of T-cell subsets in patients with psoriasis and an expansion of the helper T-cell subset in an untreated patient with pemphigus. Immunofluorescence and immunoperoxidase techniques used in conjunction with highly specific monoclonal antibodies have been shown to be valuable for histopathologic study of dermatologic diseases.     

Immunosuppressive therapy for pemphigus vulgaris complicated by malakoplakia of the bladder

Pemphigus vulgaris is an uncommon auto-immune disease which responds well to treatment with corticosteroids and azathioprine. Malakoplakia is a rare granulomatous disease associated with coliform infections and an altered cellular immune response. We report a 68-year-old female patient with pemphigus vulgaris who, after 2 years on maintenance prednisone and azathioprine immunotherapy, developed malakoplakia of the bladder associated with chronic E. coli urinary-tract infection. The malakoplakia responded well to treatment with cotrimoxazole, bethanechol chloride and ascorbic acid, combined with tapering of the corticosteroid dosage. Our patient presents an uncommon but interesting complication of long-term immunosuppressive therapy for pemphigus vulgaris.     

Pemphigus Herpetiformis in Childhood

Abstract: Pemphigus herpetiformis (PH) is a rare pemphigus variant. The clinical features of this form of pemphigus resembles dermatitis herpetiformis, however, histological examination and immunofluorescence yield findings diagnostic for pemphigus. A 5‐year‐old female patient with clinical features suggestive of dermatitis herpetiformis is reported. Histopathological exam showed skin with subcorneous blisters, epidermal spongiosis containing predominantly neutrophils, few eosinophils and rare acantholytic cells. Direct immunofluorescence showed intercellular deposits of IgG and C3. The skin lesions responded poorly to dapsone associated with systemic corticosteroid therapy. A complete remission of bullous lesions was obtained with azathioprine and immunosuppressive doses of systemic corticosteroids (prednisone). A case of PH in childhood is reported here, emphasizing the rarity and young age of onset.     

Minocycline-induced hyperpigmentation in patients with pemphigus and pemphigoid

BACKGROUND: Immunosuppressive medications typically used to treat the immunobullous disorders pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid can have serious adverse effects. The tetracycline family of antibiotic drugs has been shown to be effective in the treatment of these conditions with a more favorable side effect profile. Minocycline hydrochloride use has been associated with various forms of hyperpigmentation, and its incidence is well reported in acne vulgaris and rheumatoid arthritis. We examined a series of 9 patients treated with minocycline for pemphigus or pemphigoid, most of whom have developed cutaneous hyperpigmentation. OBSERVATIONS: Seven of 9 patients treated with minocycline, 50 mg daily (1 patient) or 100 mg twice daily (8 patients), for pemphigus vulgaris, pemphigus foliaceous, or bullous pemphigoid developed hyperpigmentation, which necessitated discontinuing therapy. Five of these patients had experienced notable clinical improvement of their immunobullous disease with minocycline therapy. The average duration of treatment was 8.2 months (range, 1-25 months). The second most common adverse effect in our group was oral candidiasis, which occurred in 2 patients. CONCLUSIONS: We found a favorable response to minocycline therapy in 5 of 9 patients. However, 7 patients developed localized hyperpigmentation as early as 1 month after starting medication use. This incidence of minocycline-induced hyperpigmentation is significantly higher in immunobullous disease than in acne vulgaris or rheumatoid arthritis. This increased incidence may be related to an increase in pigment deposition complexed with collagen during the remodeling process, subclinical inflammation, or glucocorticosteroid-induced skin fragility. The hyperpigmentation process was reversible, as most of our patients had fading of their pigmentation after minocycline cessation.     

Pesticide-associated pemphigus vulgaris

We present a 40-year-old man with occupation-induced pemphigus vulgaris (PV). He developed PV within days of a one-time heavy exposure to fumes of burning glyphosate, a broad-spectrum nonselective pesticide. This exposure suggests acute cutaneous contact as a stimulus in the development of his pemphigus. While the patient initially required mycophenolate mofetil and prednisone therapy, he has since eliminated contact with pesticides and has been successfully tapered off systemic medication. We discuss the case and review concepts of inducible PV by pesticides and physical cutaneous injury.     

Rituximab as a dual therapeutic option for pemphigus and primary cutaneous B‐cell lymphomas: Two case reports

It is known that individuals with immune dysregulation have an increased risk of non‐Hodgkin lymphoma. This association has been proven for pemphigus as well as for other autoimmune disease. We describe the development of cutaneous B‐cell lymphoma in two patients affected by long‐standing pemphigus vulgaris and pemphigus foliaceus (i.e., characterized by histological and immunopathological features different from those of paraneoplastic pemphigus). In both cases, a therapy with rituximab allowed to achieve the complete remission for the lymphoproliferative disease (never recurred at follow up) and a substantial long‐term improvement of the clinical manifestations of pemphigus, although persistent to serological disease and occasional recurrences. We suggest that clinicians should consider that patients with long‐standing pemphigus, both vulgaris and foliaceus, may develop primary cutaneous B‐cell lymphomas, as shown in our report, and in these cases the treatment with rituximab is elective, providing a therapeutic option for both low‐grade or follicular, CD20‐positive, B‐cell non‐Hodgkin lymphomas and pemphigus. Nevertheless, as shown in our cases, a constant surveillance for pemphigus is necessary.     

Paraneoplastic pemphigus associated with fatal bronchiolitis obliterans and intractable mucosal erosions: Treatment with cyclosporin in addition to steroid,rituximab and intravenous immunoglobulin

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease that presents as severe mucosal erosions and variable cutaneous lesions and is primarily associated with hematologically malignant or benign diseases. A 59‐year‐old Japanese woman presented with oral, ocular and vaginal mucosal erosions and erythema as well as blistering on her trunk and limbs. She developed bronchiolitis obliterans; lymphadenopathy in the cervical, subclavian, para‐aortic and intraperitoneal regions; and splenomegaly. PNP with B‐cell lymphoma was diagnosed. She was treated with two courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R‐CHOP) for B‐cell lymphoma, rituximab once every 3 weeks for five cycles, steroid pulse therapy, oral prednisolone, cyclosporin and high‐dose i.v. immunoglobulin. The B‐cell lymphoma was in remission after two courses of R‐CHOP treatment. Although her skin erythema and blistering were also improved, the mucosal erosions and bronchiolitis obliterans gradually worsened. The patient died of bronchiolitis obliterans after 6 months of hospitalization. Because a cellular immune response is thought to be involved in the pathogenesis of PNP, cyclosporin therapy is expected to aid in suppressing the cellular response. In this case, however, the patient's mucosal lesions and bronchiolitis obliterans were not improved by regular administration of cyclosporin therapy.