Antibody deposits in Tzanck smears in pemphigus vulgaris

Forty-three patients, including 24 males and 19 females between 5 and 62 years of age, having pemphigus vulgaris (27), pemphigus foliaceus (1), bullous pemphigoid (3), chronic benign bullous dermatosis of childhood (2) and herpes zoster (10) were included in this study. Tzanck smears were prepared from the floor of the blisters in these patients by deroofing the bullae, and the slides were stored without fixation at room temperature for 1 to 10 days. Immunofluorescence staining was done with FITC-conjugated anti-human IgG. Twenty-one cases having pemphigus vulgaris and 1 case having pemphigus foliaceus showed bright green fluorescence on the membrane of acantholytic cells. No epithelial cells were seen in smears from bullous pemphigoid and chronic benign bullous dermatosis of childhood, whereas epithelial cells were seen in 10 cases of herpes zoster. These stained negative with anti-IgG. Storage of the prepared smears for 1-10 days did not seem to affect the results of immunofluorescence. Tzanck smears can be used as an easy substitute for skin/mucosal biopsy for the direct immunofluorescence test.     

Present problems in school health

The clinical, histopathological, and electron microscopical characteristics of "transient acantholytic dermatosis" (Grover, 1971) are described. Clinically, there are papules with smooth or keratotic surfaces and sometimes papulovesicles. The lesions are mainly distributed on the trunk predominantly of male patients past the age of 40. The disease usually disappears within weeks, but rarely may be protracted. Histologically, focal changes with the epidermis of Dariertype, Hailey-Hailey-type, pemphigus (vulgaris or foliaceus)-type, or spongiotic-acantholytic type, often in combination, are found. This disease seems to be common. Its distinctiveness should be confirmed by further observations.     

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Most of the clinical, histological and immunohistological features of fogo selvagem resemble those of idiopathic pemphigus foliaceus (PF). Both diseases are clinically characterized by small flaccid bullae evolving into to scaly and crusted lesions, sometimes with pustules, mainly in seborrheic areas of the skin. Mucosal surfaces are mostly spared. The main histologic feature of endemic pemphigus foliaceus is a subcorneal acantholytic blister. Standard immunofluorescence studies demonstrate intercellular IgG deposits throughout the entire epidermis. These IgG antibodies are mainly of the IgG4-subclass. Almost all patients have circulating IgG-autoantibodies in their serum directed against stratified epithelial desmosomes. The fogo selvagem autoantibodies and the PF antibodies are directed against the 160 kD desmosomal glycoprotein desmoglein 1 which together with plakoglobin (85 kD) forms a complex of adhesion proteins with desmosomes of stratified epithelia. Fogo selvagem occurs in endemic foci in some areas of Brazil and possibly in neighbouring South American countries, very often in children, adolescents and young adults. The etiology of fogo selvagem is still unknown. The frequent association with insect bites has lead to the concept of fogo selvagem being a transmissible disease with acquired immunity in adulthood. However, the infectious agent and possible vectors have not yet been identified.     

Incidental acantholysis

The incidental finding of microscopic foci of acantholytic dyskeratosis, reproducing the histological pattern of Darier's disease, has been the subject of a number of papers in the last few years. In contrast, the incidental finding of other types of acantholysis has not been mentioned in the literature. In the last 5 years, we have noticed such a microscopic finding in 14 biopsy specimens (0.15% of our cutaneous specimens). they were from 13 patients (7 men and 6 women); their ages ranged from 37 to 79 years (mean, 63). Three lesions were located on the head, 7 on the trunk, and 4 on the limbs. The histological diagnoses were basal cell carcinoma (6 cases), keratoacanthoma (2 cases), psoriasis (2 cases), elastolytic granuloma, acral arteriovenous angioma, tinea corporis, and leukocytoclastic vasculitis (1 case each). The histological patterns of the acantholytic foci simulated pemphigus vulgaris (9 cases), superficial pemphigus (1 case), Hailey-Hailey disease (3 cases), and unclassifiable acantholysis (1 case). None of the patients had familial or personal history of acantholytic disorders. We propose a classification of the primary acantholytic disorders based on both their acantholytic pattern and their clinical extent.     

Bullous IgA linear dermatosis of children in Mali

INTRODUCTION: Bullous IgA linear dermatosis is relatively frequent in children in Africa. The aim of this study was to evaluate the frequency of this disease among autoimmune bullous diseases in children in Mali. PATIENTS AND METHODS: Children with chronic bullous disease seen at the Marchoux Institute in Bamako and for whom direct immunofluorescence of the perilesional skin demonstrated immunoglobulin and/or complement deposits were included in the study population. RESULTS: Twelve children were included. Direct immunofluorescence showed linear IgA deposit along the dermo-epidermal junction in 10, once with a pemphigoid aspect and once with a pemphigus aspect. The skin lesions in the children with linear IgA deposits were stereotypic: disseminated bullae, rosettes (9 out of 10), involving the external genital organs (10/10), the limbs, the face and the trunk. Histology showed subepidermal bullae (10/10), with neutrophil papillar abscesses (9/10). Indirect immunofluorescence of the cleaved skin NaCl in 5 patients showed that the cleavage always lied at the roof of the cleavage. All the children responded to dapsone (1 to 2.5 mg/kg/d) which gave complete (7/10), or incomplete remission. Local corticosteroids were used in 2 patients and general corticosteroids in 1. DISCUSSION: This confirms the frequency of bullous IgA linear dermatosis in Africa, in contrast with uncommon dermatitis herpetiformis. Diagnosis is facilitated with immunofluorescence. The low cost of this test makes it a useful diagnostic tool in these countries.     

Paraneoplastic pemphigus with tracheobronchial involvement

BACKGROUND: Paraneoplastic pemphigus is a bullous skin disease with characteristic polymorphous clinical presentation and precise histological and immunological features. We report a case of paraneoplastic pemphigus associated with chronic lymphoid leukemia involving the tracheobronchial epithelium. CASE REPORT: A patient with chronic lymphoid leukemia developed pluriorificial lesions. There were several conjunctival, buccal and genital erosions associated with erosive plaques on the trunk, Nikolski's sign and bullous lesions suggestive of paraneoplastic pemphigus. Histology examination of a bulla showed intraepidermal blistering and suprabasal acantholysis. Direct immunofluorescence evidenced intercellular IgG and C3 deposits. Search for anti-intercellular substance antibodies was positive with fluorescence on specific paraneoplastic pemphigus substrates. At immunotransfer, the serum recognized several bands corresponding to 250, 230, 210 and 190 kD antigens, confirming the diagnosis of paraneoplastic pemphigus. Several days later, the patient's general condition deteriorated with bronchorrhea. Bronchial endoscopy visualized ulceronecrotic plaques. Tracheal biopsy evidenced acantholytic cells and intraepithelial cleavage. General corticosteroid therapy was initiated and led to improvement of the skin lesions but the patient died rapidly from pneumonia. Autopsy confirmed the presence of epithelial cleavage and acantholysis involving the trachea and bronchi. DISCUSSION: This case illustrates the difficulty of diagnosing paraneoplastic pemphigus in the early stages. The pluriorificial lesions were suggestive of a Stevens-Johnson syndrome. Besides the genital, conjunctival and buccal mucosa, other mucosa can be involved. In our case, despite the absence of an immunological element, histology was highly suggestive of specific tracheobronchial localizations. The presence of such lesions, which should be searched for in all cases with bronchopulmonary manifestations, worsens the prognosis.     

A paraneoplastic mixed bullous skin disease associated with anti-skin antibodies and a B-cell lymphoma

BACKGROUND: The full spectrum of bullous diseases associated with underlying cancers remains to be fully defined. OBSERVATION: We describe a patient with a mixed bullous disease exhibiting combined features of cicatricial pemphigoid and pemphigus and associated with a B-cell lymphoma producing an IgM paraprotein to intercellular antigens in human skin. The patient had the clinical features of cicatricial pemphigoid and the histologic and immunofluorescence abnormalities of both cicatricial pemphigoid and pemphigus. These included oral and cutaneous erosions; ocular scarring; subbasal and acantholytic intraepidermal bullae; and circulating and tissue-fixed basement membrane zone and intercellular antibodies. The antibodies were directed to a 140-kd antigen in dermal extracts of skin split with 1 mol/L of sodium chloride and to antigens with approximate molecular weights of 150, 180, 230, and 285 kd in the dermal extract. In contrast to paraneoplastic pemphigus, the intercellular antibodies did not react to mammalian bladder. The intercellular antibodies were of the IgM class and were associated with the paraprotein produced by the malignant B cells. CONCLUSIONS: We believe that this condition represents a novel bullous disease, which we refer to as paraneoplastic mixed bullous disease. This condition illustrates that distinct bullous diseases are associated with paraneoplastic syndromes and that at least one possible mechanism for such eruptions is the production of anti-skin antibodies by malignant B cells.     

Pemphigoid vegetans. An immunoelectron microscopic study

INTRODUCTION: Pemphigoid vegetans is a rare disease. It has a clinical resemblance to pemphigus vegetans, but there are histological and immunopathological features of bullous pemphigoid. CASE REPORT: We describe a case in a 57-year-old-man who had developed intertriginous vegetating plaques. Histologic examination of a skin biopsy specimen and direct immunofluorescence microscopy of a biopsy specimen were those of bullous pemphigoid. Immunoblot studies and indirect immunofluorescences of salt-split skin were negative. Direct immunoelectron microscopy was consistent with bullous pemphigo?d. DISCUSSION: Only five cases have been reported. We describe the first case including direct immunomicroscopic findings which suggest that pemphigoid vegetans is a subtype of bullous pemphigoid. The other interest was a remarkable improvement with tetracyclines.     

A comparison of needs assessed by staff and by an epidemiologically representative sample of patients with psychosis

A 34-year-old healthy woman presented with a 15-month history of persistent, nonhealing vulvar ulcerations due to herpes simplex virus (HSV) type 2. Extensive dermatologic workup and serial skin biopsies failed to reveal an underlying vulvar dermatosis or autoimmune bullous disorder. Virologic studies revealed resistance to acyclovir in vitro due to deficiency in thymidine kinase activity. Serum antibody to human immunodeficiency virus was negative on two occasions, separated by 1 year. Immunologic evaluation showed normal HSV-specific proliferative and CD8 cytotoxic T lymphocyte responses as well as normal NK cell function. Vulvar lesions failed to heal in association with trials of topical trifluorothymidine and oral valacyclovir but resolved completely with the application of 1% foscarnet cream. No recurrence of HSV has been observed in 24 months of follow-up to date.     

Role of CD4+ and CD8+ T cells in regulating the chronic development of liver injury induced by delayed-type hypersensitivity to picryl chloride

Lectins were used to investigate the cell surface oligosaccharide expression in normal vulvar epithelium from premenopausal and postmenopausal volunteer women. In addition, histologically normal epithelium adjacent to high-grade vulvar intraepithelial neoplasia (VIN III) and adjacent to vulvar tumors was examined with lectins for evidence of a possible "field change" surrounding these vulvar lesions. Seventeen vulvar biopsies were obtained prospectively from volunteer women, and 20 and 40 cases, respectively, of VIN III and vulvar squamous cell carcinoma were randomly chosen from pathology archives. Thirteen of the 20 VIN cases and all 40 vulvar carcinomas contained at least 2 cm of histologically normal-appearing epithelium adjacent to the vulvar lesion suitable for analysis. No alterations to lectin binding in normal vulvar epithelium with respect to patient age, menopausal status, phase of menstrual cycle, estrogen therapy, or history of cervical intraepithelial neoplasia were shown. ABO blood group antigen status affected epithelial binding for lectins HPA and UEAI (p < 0.005 and p < 0.001, respectively). In addition, lectins SNA, MPA, and LCA identified markers of cellular differentiation and maturation. T-antigen expression (as shown by the lectin PNA) was almost universally present in histologically normal epithelium adjacent to VIN and vulvar tumors, contrasting with the lack of PNA binding in normal vulvar epithelium from volunteer women (p < 0.001 and p < 0.001), a finding suggestive of a local "field change" surrounding preinvasive and invasive vulvar lesions.     

Langerhans cell histiocytosis

The authors present a rare case of Langerhans cell histiocytosis in a 31 year old female patient with vulvar, peri-anal and oral lesions, diabetes insipidus, pulmonary skin and bone infiltrations. Skin biopsy immunohistochemistry presented positive S100 protein and vimentin, but the diagnosis was done with the demonstration of Birbeck granules with electronic microscopy. The treatment was based on systematical chemotherapy although vulvar lesion has a bad response to chemotherapy.     

Alien hand syndrome: influence of neglect on the clinical presentation of frontal and callosal variants

Three patients with mesial frontal and extensive callosal lesions due to anterior cerebral artery infarction manifested an alien hand syndrome (AHS) with varied features. Patient 1 with left hemispheric lesion showed right hand's impulsive reaching and grasping and left hand's antagonistic movements to the right (intermanual conflict; IMC). Patients 2 and 3 with right hemispheric lesion manifested a left hemihypokinesia which was thought to have suppressed the frequency and amplitude or even the occurrence of left hand's reaching and grasping. IMC and other left hand's non-antagonistic, irrelevant movements to the right remained. Because the term "IMC" is often misused and not strictly defined, its association with right hand's reaching and grasping is quite uncommon, its significance as a sign of callosal disconnection is not well validated, and because left hand's reaching and grasping tend to be suppressed by motor neglect, a trend may then develop for the right hand to be the sole focus of pathological behaviour in patients with the so-called frontal AHS (Feinberg, Schindler, Flanagan et al., 1992).     

Nocardia abscess of the choroid plexus: clinical and pathological case report

OBJECTIVE: Cerebral Nocardia abscesses are rare, accounting for approximately 1 to 2% of all cerebral abscesses. Prompt aggressive surgical treatment involving craniotomy and excision of these lesions has been advocated by many authors, because these lesions have significantly higher morbidity and mortality rates than do most other cerebral abscesses. We report an atypical presentation of cerebral nocardiosis localized to the choroid plexus of the lateral ventricle. CLINICAL PRESENTATION: A 56-year-old man presented with a 3-week history of fever, cough, and progressive headache and an ensuing 3-day history of progressive lethargy, confusion, and gait ataxia. Radiographic studies demonstrated a loculated contrast-enhancing left lateral ventricular lesion with significant perilesional parenchymal edema that was thought preoperatively to be a neoplasm. INTERVENTION: The patient underwent a craniotomy for resection of the lesion. Intraoperatively, a reddish gray lesion with purulent exudate was encountered within the left lateral ventricle intimately adherent to the choroid plexus as well as to the ependyma and subependymal veins. A frozen section demonstrated an organizing abscess wall. The lesion was resected in its entirety, and multiple cultures were sent for analysis. CONCLUSION: Microbiology cultures grew Nocardia asteroides. A course of intravenous antibiotics was started, which included trimethoprim-sulfamethoxazole, amikacin, and ceftriaxone. Two weeks after surgery, at the time of discharge, the patient's neurological status had improved considerably. Although Nocardia abscesses have been documented to occur throughout the central nervous system, the presentation of a lesion confined to the choroid plexus of the lateral ventricle with significant parenchymal edema is unusual and demonstrates that Nocardia abscesses must be considered in the differential diagnosis of a contrast-enhancing intraventricular mass lesion involving the choroid plexus.     

Community health nursing: can being self-employed work for you in home care?

BACKGROUND: Vulvar involvement in Crohn's disease is uncommon. The elementary lesion is usually an ulceration: 44 cases have been reported in the literature. In 20 p. 100 of the cases, vulvar involvement is the only manifestation of the disease. We report 3 new cases of vulvar lesions in Crohn's disease. CASE REPORTS: The first case had vulvar lesions which complicated ileocolic Crohn's disease, in the other two cases there were no digestive manifestations. One patient developed voluminous edema of the right labium. The diagnosis of Crohn's disease of the vulva was suggested by the characteristic lesions, presence of epithelioid and giant cell granuloma at histology examination of the vulva specimen and finally on rapidly favorable course after treatment with sulfasalazine. The ulcers regressed with medical treatment but remission was temporary with recurrence at treatment withdrawal. DISCUSSION: These cases underline the difficulties encountered in establishing the diagnosis of Crohn's disease in patients who develop vulvar ulcerations alone with no signs of digestive disease and emphasize the difficult problem of long-term control.     

Hereditary sensory autonomic neuropathy--type II in siblings

An experimental investigation has lately shown that certain allyl compounds of garlic are able to provoke acantholysis in normal human skin cultured in vitro. The acantholytic effect has been more prominent in the samples from DR4+ donor. We here report a case of superficial pemphigus which appeared spontaneously in a DR4,14+, 49-year-old man and which ran a course that proved to be affected by dietary factors, in particular by the consumption of garlic. In the absence of a conventional treatment and on a garlic-free diet only, the disease ceased for several months. Soon after an unintentional dietary test with a strongly and presumable garlic-spiced fish meal, the pemphigus recurred. Nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing or perpetuating pemphigus in genetically predisposed individuals.     

Functional involvement of urokinase-type plasminogen activator receptor in pemphigus acantholysis

Urokinase-type plasminogen activator (uPA) has been well documented in the development of pemphigus acantholysis. The function of its receptor (uPA-R) in pemphigus acantholysis has only recently attracted attention. Increased expression of uPA-R has been demonstrated in pemphigus vulgaris. In this study, we have further explored the functional involvement of uPA-R in pemphigus acantholysis. Our results show that uPA-R expression is significantly increased in acantholytic foci of pemphigus vulgaris and pemphigus foliaceus but not in bullous pemphigoid or normal skin specimens; the expression of uPA-R in cultured human keratinocytes is subjected to regulation by pemphigus vulgaris IgG but not by pemphigoid IgG or normal human IgG; furthermore, anti-uPA-R monoclonal antibody effectively inhibits pemphigus vulgaris IgG induced acantholysis in skin organ cultures. These data suggest that uPA-R may play an important role in the pathogenesis of pemphigus acantholysis.     

Progressive multifocal leucoencephalopathy. Observation with predominant pontocerebellar lesions and association with congenital immune deficiency]

A young woman presented a mixed congenital and familial immunodeficiency syndrome consisting in an absence of IgA and lowered levels of IgG and IgM, with a defect in cellular immunity. She had a mild malabsorption syndrome with slight alterations of the jejunal mucosa. Non-caseating tuberculoid granulomata were found in skin lesions, in lymph nodes and in the spleen. At age 27 the patient died of a neurological disease of 4 months duration. Autopsy revealed a very widespread demyelinating process involving mainly the right cerebellar hemisphere but also most of the pons and left cerebellum, with the typical morphologic characters of PML. In the hemispheres lesions were limited to microscopical "microglial nodules" with discrete demyelination. A review of 86 published cases of PML revealed 9 other cases in which lesions showed a strong predilection for the subtentorial territories. This sampling allows for tha assumption that some 11% of the cases of PML have this particular lesion distribution. Other pertinent features of this case are briefly discussed.     

Relationship between keratinocyte adhesion and death: anoikis in acantholytic diseases

Loss of attachment to the substratum may trigger apoptosis in epithelial cells (anoikis). It is less clear whether apoptosis may be triggered by disruption of cell-cell contacts, as happens in acantholytic diseases. Biopsy specimens were obtained from the border of skin lesions from four patients with pemphigus vulgaris (PV), four patients with pemphigus foliaceus (PF), three patients with Darier's disease (DD), two patients with Darier's-type Grover's disease (GD), and two patients with benign familial pemphigus Hailey-Hailey disease (HH). Control skin was obtained from five healthy volunteers. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) and confocal laser scanning microscopy was employed to detect the nuclei containing fragmented DNA in apoptotic cells. In PV and PF, TUNEL-stained apoptotic keratinocytes were abundantly present in the regions of acantholysis and in the cohesive epidermis below the blisters. Apoptotic keratinocytes had pyknotic, condensed nuclei. In DD, GD and HH, the number of TUNEL-stained keratinocytes was lower, apoptotic keratinocytes were confined to the regions of dyskeratosis and acantholysis, and pyknosis was absent. In conclusion, disruption of cell-cell contacts in acantholytic skin disorders may in some cases cause apoptosis of keratinocytes. Further studies are needed to determine whether the observed differences in the pattern of apoptosis are due to targeting of different junctional elements (adherens junctions in PV and PF versus desmosomes in DD, GD and HH).     

Scleroderma-like patch on the thigh in infants after vitamin K injection at birth: six observations

INTRODUCTION: Texier's disease or pseudosclerodermatous reaction after intramuscular injection of vitamin K1 is well known in adults although only 1 report of a case in a newborn was found in the literature. We report 6 cases. CASE REPORTS: Six infants (4 boys, 2 girls) developed "peau d'orange" skin lesions after the age of 6 months which was localized in the lower third of the medial aspect of the thigh. Initial rapid locoregional extension was followed by stabilization and then regression. In all 6 cases, histology showed lesions of the fascia and/or the deep hypoderma associated with variable mononuclear inflammatory infiltration and hyalin fibrosis. When performed, immunological studies (complement fixation, search for autoantibodies) were always negative or normal. No visceral involvement was found. DISCUSSION: A pseudosclerodermatous lesion of the lower third of the thigh occurred in 6 infants at the site of an intramuscular injection of vitamin K1 administered at birth. The history, clinical manifestations, histology and outcome of these cases are compatible with the diagnosis of Texier's disease. We discuss the role of the solvent in the Roche vitamin K1 injection. The pathogenesis of this side effect remains unknown. CONCLUSION: Texier's disease in infants after injection of vitamin K1 at birth is a stereotypic dermatosis. Diagnosis is based on history and clinical presentation. The causal effect of injectable vitamin K1 should be entertained whenever pseudosclerodermatous lesions are observed in a young child.     

Intraepithelial neoplasia of the vulva

Intraepithelial neoplasia of the vulva is being seen with increasing frequency. Awareness of this should prompt the clinician to carefully inspect the vulva on all patients. Reports strongly suggest a relationship between infection with human papillomavirus and vulvar intraepithelial neoplasia. The frequency with which this disease progresses to invasive carcinoma is unknown at present. However, it is obvious that it does occur. Both the warty and basaloid types of vulvar intraepithelial neoplasia are associated with HPV infection and are often associated with invasive squamous cell carcinoma of the vulva demonstrating similar morphologic characteristics. These changes are seen more often in younger women who smoke than in the older nonsmoking woman whose lesions do not appear to be HPV related. Both local excision and the carbon dioxide laser are effective for treating vulvar intraepithelial neoplasia. The choice of which approach to take depends upon the location and size of the lesion or lesions. Whichever approach is utilized, preservation of the normal vulvar anatomy and function are of paramount importance.