Dermoscopic approach for differential diagnosing of autoimmune bullous disease: pemphigus vulgaris, pemphigus foliaceus, and IgA pemphigus.

INTRODUCTION: Dermoscopy is a noninvasive technique for the evaluation of different pigments and microstructures of the epidermis, dermoepidermal junction, and papillary dermis that are not apparent to the naked eye, which therefore improves diagnostic accuracy. AIM OF THE STUDY: This study aims to describe the characteristic dermoscopic features of bullous diseases and analyze the characteristic dermoscopic features of bullous diseases of the skin and hair. PATIENTS AND METHODS: A descriptive study was conducted to describe and analyze the characteristic dermoscopic features of bullous diseases in the Zagazig University Hospitals. RESULTS: This study enrolled 22 patients. Dermoscopy revealed yellow hemorrhagic crusts in all patients and white yellow structure with red halo in 90.9% of patients. Pemphigus vulgaris patients were identified by the presence of dermoscopic clues such as bluish deep discoloration, tubular scaling, black dots, hair casts, hair tufts, yellow dots with whitish halos (fried egg sign) and yellow follicular pustules that are not seen in pemphigus foliaceus and IgA pemphigus. DISCUSSION: Dermoscopy is an important tool that serves as a link between clinical and histopathological diagnoses, and it can easily be used in daily practice. Several suggestive dermoscopic features can help in the differential diagnosis of autoimmune bullous disease but only after making a provisional clinical diagnosis. Dermoscopy is a very useful tool in the differentiation of pemphigus subtypes.

Pénfigo vulgar / Pemphigus vulgaris

Imágenes

Thoracoabdominal computed tomography neoplasia detection in patients with paraneoplastic pemphigus: the importance of collaboration between specialists.

INTRODUCTION: Paraneoplastic pemphigus (PNP) is an autoimmune disorder that is almost always linked to an underlying neoplasia. General radiologists are usually not aware of what kind of neoplasia can be associated with PNP. Therefore, this study evaluates the effect of a dermatology lecture on radiologists' neoplasia diagnosis performance. METHODS: Two radiologists evaluated thoracoabdominal computed tomography (CT) examination images of 43 patients with PNP in separate reading sessions blinded to each other's assessments. Six months after the first CT image evaluation session, the two radiologists attended a lecture by two dermatologists about PNP, and 6 months later the two radiologists assessed the same CT examinations again. RESULTS: Statistical analysis showed statistically significant differences in CT sensitivity between the first and the second round of image evaluation for both radiologists (reader 1: p = 0.0313; reader 2: p = 0.0156). CONCLUSIONS: This is the first study to evaluate the effectiveness of a dermatology lecture on diagnostic performance. It is very important for radiologists to be familiar with the particular neoplasms that can be associated with PNP because this can have a direct clinical impact on diagnostic performance.

Ultra-high frequency ultrasound in the differential diagnosis of oral pemphigus and pemphigoid: An explorative study.

OBJECTIVES: Intraoral ultra-high frequency ultrasound (UHFUS) is an emerging technique in oral medicine, due to its possibility to provide submillimeter resolution imaging of superficial mucosal structures. In this study, the potential role of UHFUS in the diagnosis of oral pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP) is assessed. MATERIALS AND METHODS: Consecutive patients with suspected oral PV or MMP were enrolled. All patients underwent clinical examination, laboratory tests, intraoral UHFUS scan, and biopsy. Histology and direct immunofluorescence were set as benchmark for diagnosis confirmation. The sensitivity and specificity of UHFUS compared to histology were assessed. Mann-Whitney test was performed to evaluate the presence of differences in the echogenicity of PV and MMP. P-value was set at P < 0.05. RESULTS: Twenty-five patients were included. Thirteen patients were diagnosed with PV, and twelve with MMP. The UHFUS features of PV and MMP lesions were described. Image analysis showed statistically significant differences between the echogenicity of PV and MMP lesions (P < 0.05). Good concordance between UHFUS and histology was found. UHFUS showed 75% sensitivity in the diagnosis of PV and 66.7% in the diagnosis of MMP. CONCLUSIONS: UHFUS appears a valuable tool in the diagnosis of PV and MMP. Although histology and immunofluorescence remain the gold standard, UHFUS role in the diagnostic algorithm of PV and MMP seems promising as a chair-side tool consistently enhancing clinical evaluation of oral bullous lesions.

Simultaneous immunofluorescence and histology in pemphigus vulgaris using ex vivo confocal laser scanning microscopy.

Ex vivo confocal laser scanning microscopy (ex vivo CLSM) provides rapid, high-resolution imaging and immunofluorescence examinations of the excised tissues. We aimed to evaluate the applicability of ex vivo CLSM in histomorphological and direct immunofluorescence (DIF) examination of pemphigus vulgaris (PV). 20 PV sections were stained with fluorescent-labeled anti-IgG and anti-C3 using various dilutions and incubation periods. Subsequently, the determined ideal staining protocol was applied on 20 additional PV and 20 control sections. Ex vivo CLSM identified intraepidermal blisters and acantholytic cells in 80% and 60% of PV patients, respectively. The sensitivity of ex vivo CLSM in detecting intraepidermal fluorescence was 90% both with IgG and C3. The specificity of staining for IgG and C3 was 70% and 90%, respectively. Histomorphological and immunofluorescence features of PV could be detected within the same ex vivo CSLM session showing a comparable performance to conventional histopathology and DIF microscopy.

Pemphigus scalp lesions: is trichoscopy helpful in clinical diagnosis?

BACKGROUND: Pemphigus is an autoimmune intraepidermal bullous disease which can affect skin and∕or mucous membranes. Trichoscopy is a non-invasive tool that can help in the clinical diagnosis especially if the patient is presented with only scalp lesions. We conducted this study to investigate the trichoscopic features of pemphigus scalp lesions. METHODS: A total of 100 patients with confirmed diagnosis of pemphigus entered the study; Seventy-nine patients were diagnosed as pemphigus vulgaris (PV) and 21 as pemphigus foliaceus (PF). Trichoscopy of the scalp lesions was performed, and three dermatologists examined separately the trichoscopic images of each patient. The results were re-checked simultaneously by the examiners. Association between variables was analyzed by using different tests including: chi-square test or Fischer's exact test, independent T-Test or Mann-Whitney nonparametric test and logistic regression model when applicable. RESULTS: Mean age of the patients was 45.41 ± 11.13 years, and 58% of cases were male. The most common trichoscopic features observed among all cases were diffuse scaling (71/100), presence of any types of vessels (67/100), and extravasation (63/100). Positive anagen pull test, extravasation, yellow hemorrhagic crust, and polymorphic vessels were more commonly seen in PV than PF cases (P value < 0.05), and by having data of these variables, we can differentiate between PV and PF scalp lesions with 74% sensitivity and 91% specificity. CONCLUSION: Trichoscopy can help in clinical diagnosis of pemphigus scalp lesions but should be followed by other modalities such as biopsy and direct immunofluorescence for definite diagnosis.

Investigation of using very high-frequency ultrasound in the differential diagnosis of early-stage pemphigus vulgaris vs seborrheic dermatitis.

BACKGROUND: Early-stage pemphigus vulgaris (PV) often manifests as erythema alone. We hypothesized that very high-frequency ultrasonography (VHFUS) features could simplify the differential diagnosis of early-stage pemphigus vulgaris versus seborrheic dermatitis (SD). MATERIALS AND METHODS: Fourteen patients with SD or early-stage PV were recruited from our outpatient clinic during 2016-2019. We used 50-MHz VHFUS to image the erythema on the patients' scalp, face, chest, and back and retrospectively evaluated their ultrasonographic features. RESULTS: Very high-frequency ultrasonography images of early-stage PV showed enhanced epidermal echo (8/14, 57%), linear or oval intra-epidermal hypoechoic/anechoic areas (12/14, 86%), linear anechoic areas at the dermal-epidermal junction (14/14, 100%), reduced echo of superficial to whole dermis (9/14, 64%), and slightly increased dermal thickness (14/14, 100%). The intra-epidermal hypoechoic/anechoic bands (100%) showed the greatest specificity. VHFUS images of SD showed enhanced epidermal echo (7/14, 50%), epidermal unevenness (7/14, 50%), linear anechoic bands at the dermal-epidermal junction (8/14, 57%), reduced middle dermis echo (10/14, 71%), and slightly increased dermal thickness (10/14, 71%). The epidermal unevenness (100%) had the greatest specificity. There was a significant difference (P < .05) between early-stage PV and SD regarding the proportion of linear intraepithelial hypoechoic/anechoic bands and linear anechoic areas at the dermal-epidermal junction. CONCLUSIONS: Early-stage PV and SD have relatively specific VHFUS erythematous manifestations. Intra-epidermal hypoechoic/anechoic bands for early-stage PV and epidermal unevenness for SD were most specific. VHFUS contributes to the differential diagnosis of PV and SD by highlighting their features, that is, intra-epidermal hypoechoic/anechoic bands and linear anechoic areas at the dermal-epidermal junction.

Optical coherence tomography imaging of oral mucosa bullous diseases: a preliminary study.

OBJECTIVES: Optical coherence tomography (OCT) is a non-invasive technique based on optical imaging with a micrometre resolution. The purpose of this study is to investigate the potential role of OCT in evaluating oral mucosa bullous diseases. METHODS: two patients with bullous pemphigoid (BP) and one patient with pemphigus vulgaris (PV) were examined and images of their oral lesions were performed using OCT. RESULTS: In OCT images, the BP blister has a clearly different morphology from the PV one compared to the blistering level. CONCLUSION: This exploratory study suggests that the OCT is able to distinguish epithelial and subepithelial layer in vivo images of healthy oral mucosa from those with bullous diseases, assisting the clinicians in differential diagnosis.The presented data are in accordance with the scientific literature, although a wider pool of cases is needed to increase statistical power. Histological examination and immunofluorescence methods remain the gold standard for the diagnosis of oral bullous diseases. In this context, the OCT can provide the clinician with a valuable aid both as an additional diagnostic tool and in the follow up of the disease.

Analysis of oral mucosa erosive-ulcerative lesions by reflectance confocal microscopy.

In vivo Reflectance Confocal Microscopy (RCM) allows to optically biopsy vital tissues, non-invasively and in real time. It results in horizontal virtual slices at a microscopic resolution and correlating with conventional histopathology. The aim of the present work is to describe RCM cellular and architectural findings in oral mucosae affected by erosive-ulcerative diseases, thus highlighting in vivo the wellknown histological peculiarities. A series of conventionally diagnosed Recurrent Aphthous stomatitis (RAS) and Pemphigus Vulgaris (PV) erosive and/or ulcerative oral lesions underwent RCM imaging to establish the application of RCM imaging to this kind of inflammatory non-tumoral lesions. A total of 12 RAS-related lesions and 8 PV-related lesions were considered. RCM imaging was capable to visualize their microscopic peculiarities, mainly inflammatory infiltrate, vessel dilation (RAS) and acantholytic cells, intraepithelial clefts and inflammatory cell carpets (PV). Despite RCM may result unnecessary to diagnose oral lesions referred to RAS and PV, its capability to highlight their main microscopic features could be advantageously used to monitor the healing or worsening of the clinical situation as well as the responsiveness/refractoriness to therapy.

Paraneoplastic pemphigus and myasthenia gravis as the first manifestations of a rare case of pancreatic follicular dendritic cell sarcoma: CT findings and review of literature.

BACKGROUND: Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm that originates from follicular dendritic cells in lymphoid tissue while paraneoplastic pemphigus (PNP) is an autoimmune blistering disease associated with neoplasms. Pancreatic FDCS associated with PNP and myasthenia gravis (MG) is even rarer and highly malignant. We present the clinical data, pathological materials and computed tomography (CT) features of a rare case of this disease. CASE PRESENTATION: A 49-year-old woman presented with repeated ptosis of both eyelids, oral ulcers and erosions. Her laboratory results showed a slight elevation of CA125 and positivity of some autoimmune antibodies. CT revealed a round solid mass with central necrosis in the pancreatic tail. The solid component of the mass showed slight enhancement and serpentine feeding arteries in the arterial phase, moderate enhancement with a draining vein around the tumor in the portal venous phase and persistent enhancement in the delayed phase. Surgical resection was performed, and the pathological diagnosis was FDCS. However, the patient died of inability to excrete sputum and occlusion of the respiratory tract. CONCLUSIONS: Pancreatic FDCS manifested as PNP and MG is very rare. Its CT features are not specific, and the disease should be differentiated from neuroendocrine tumors, solid pseudopapillary neoplasms and acinar cell carcinoma.

Reflectance confocal microscopy and optical coherence tomography for the diagnosis of bullous pemphigoid and pemphigus and surrounding subclinical lesions.

BACKGROUND: Diagnosis of bullous pemphigoid (BP) and pemphigus is based on clinical features, histology, immunofluorescence and laboratory data. OBJECTIVES: To evaluate features of BP and pemphigus at reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in order to provide a rapid non-invasive bed-side diagnosis. Secondary objective was to evaluate the detectability of clinically non-visible lesions. METHODS: This was an observational, retrospective, multicentre study in which patients with suspicious lesions for BP or pemphigus underwent clinical assessment, RCM, OCT, blood tests and skin biopsy for histological and direct immunofluorescence examinations from January 2014 to December 2015. A total of 72 lesions in 24 selected patients were evaluated. Additionally, apparently unaffected skin at two different distances [near (1-2 cm) and far (2-3 cm)] from each lesion was examined to test subclinical lesion detectability. RESULTS: RCM was able to detect subepidermal and intra-epidermal blisters, respectively, in 75% and 50% of the patients affected by BP and pemphigus. At OCT, the exact blister level was identified in all patients. Acantholytic cells were observed only at RCM in pemphigus (62.5%). Fibrin deposition inside the blisters was only found in BP, evidenced both at RCM and OCT. Among patients with BP, subclinical blisters were detected in nine (9.4%) clinically healthy skin, while among patients with pemphigus were observed in 10 (20.8%) apparently unaffected skin. CONCLUSION: RCM and/or OCT provide useful information for a rapid diagnosis of BP and pemphigus and for the identification of biopsy site. Combined use of RCM and OCT is optimal because associates the higher resolution of RCM with the greater penetration depth of OCT. OCT could be an optimal tool for treatment monitoring, especially in the cases of subclinical lesions. However, histopathologic and immunologic examinations remain the gold standard for establishing the final diagnosis.

Trichoscopy - a useful tool in the preliminary differential diagnosis of autoimmune bullous diseases.

BACKGROUND: Scalp is a common location of autoimmune bullous diseases. Trichoscopy is a noninvasive method for diagnosing hair and scalp diseases. Data on trichoscopy in autoimmune bullous diseases are limited to the studies on pemphigus including a small number of patients. Trichoscopic characteristics of bullous pemphigoid and dermatitis herpetiformis were not reported to date. The aim of the study was to determine the value of trichoscopy in the differential diagnosis of pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, and dermatitis herpetiformis. METHODS: Trichoscopy was used to evaluate scalp lesions in 68 patients (26 with pemphigus vulgaris, 17 with pemphigus foliaceus, 17 with bullous pemphigoid, and 8 with dermatitis herpetiformis). The working magnification was 20-fold and 70-fold. RESULTS: The most frequent trichoscopic feature of autoimmune bullous diseases was extravasations. They occurred in 76.9% of patients with pemphigus vulgaris, 70.6% of patients with pemphigus foliaceus, 76.5% of patients with bullous pemphigoid, and 100% of patients with dermatitis herpetiformis. Yellow hemorrhagic crusts occurred in, respectively, 73.1%, 70.6%, 64.7%, and 35.5% of the cases. Yellow diffuse scaling and tubular scaling occurred more frequently in pemphigus foliaceus (52.9% and 41.2%, respectively). Clustered dotted vessels were characteristic for dermatitis herpetiformis (5/8, 62.5%). Dotted vessels with whitish halo were a hallmark of pemphigus vulgaris. A trichoscopic algorithm for the differential diagnosis of autoimmune bullous diseases was developed. CONCLUSIONS: Autoimmune bullous diseases present characteristic trichoscopic patterns. Trichoscopy can be regarded as a rapid in-office preliminary diagnostic method in the differential diagnosis of these diseases.

High-Frequency Ultrasound in Blistering Skin Diseases: A Useful Method for Differentiating Blister Locations.

Bullous pemphigoid and pemphigus vulgaris, which belong to the group of subepidermal and intraepidermal bullae, respectively, are two potentially devastating blistering skin diseases. We used high-frequency ultrasound (US) in 3 cases of these diseases as prototypes to study the value of high-frequency US in discriminating blister locations. Our findings showed that high-frequency US has a strong correlation with histomorphometric findings because of its high resolution, and we hope that it will be helpful for differentiating blister locations.

[Involvement of mucous membranes in autoimmune bullous diseases]. / Schleimhautbeteiligung bei blasenbildenden Autoimmunerkrankungen.

Autoimmune bullous diseases are characterized by intraepidermal or subepidermal autoantibody deposition that leads to blisters and secondary erosion. Mucous membranes are frequently affected in pemphigus vulgaris and always involved in cicatricial and mucosal pemphigoid. Mucosal lesions are detected less frequently in patients with bullous pemphigoid or epidermolysis bullosa acquisita. The diagnosis of autoimmune bullous disorders is based on determination of the subtype of autoantibodies bound in the skin and the clinical picture. Treatment is based on immunosuppression related to the type of disease and severity of the mucosal symptoms. Ocular involvement in mucosal pemphigoid and pemphigus vulgaris requires systemic treatment.

Pemphigus with features of both vulgaris and foliaceus variants localized to the nose.

We report the case of a 74-year-old man affected by an unusual variant of pemphigus. He presented with a crusty and scaly lesion of the nose. We performed reflectance confocal microscopy and optical coherence tomography on the lesion, which suggested an unexpected diagnosis of pemphigus. Therefore, to confirm our diagnostic suspicions, we executed indirect immunofluorescence and two biopsies, one for histopathological examination and one for direct immunofluorescence. Histopathological evaluation showed acantholysis with formation of clefts in the granular and spinous layers of the epidermis. Direct immunofluorescence revealed immunoglobulin G and C3 deposit to the full thickness of the epidermis. Indirect immunofluorescence showed intercellular antibodies at a titer of 1:40 in the suprabasal epidermis. The immunoblot analysis using epidermal extract revealed the presence of circulating antibodies directed to 130- and 160-kDa antigens in the patient's serum. These two antigens were evidenced from nitrocellulose membrane with colorimetric AP systems, which highlighted the presence of autoantibodies against desmoglein (Dsg)1 and Dsg3 (sodium dodecylsulfate polyacrylamide gel electrophoresis). We also performed an enzyme-linked immunoassay. All these findings suggested that this patient's pemphigus had features of both vulgaris and foliaceus variants.

Paraneoplastic pemphigus as a first sign of metastatic retroperitoneal inflammatory myofibroblastic tumor: (18)F-FDG PET/CT findings.

A 30-year-old female presented with a 3-month history of erosive stomatitis and bullous lesions, along with recurrent episodes of abdominal pain. She was found to have a retroperitoneal lump in left lumbar region. Skin biopsy revealed bullous disorder. CT guided biopsy of the retroperitoneal mass was suggestive of inflammatory myofibroblastic tumor (IMT). She was started on oral steroids and supportive care, and surgery was being planned when she developed respiratory failure. CT chest revealed vertebral metastases. PET/CT for whole body work up revealed a left para-aortic mass along with multiple skeletal metastases. The patient was kept on conservative management. After 3 months, the patient has shown clinical improvement, and an exploratory laparotomy is now being planned for the excision of the tumor, followed by chemotherapy. This case of retroperitoneal IMT is rare in terms of skeletal metastases with paraneoplastic pemphigus.

Mediastinal follicular dendritic cell sarcoma with paraneoplastic pemphigus.

Follicular dendritic cell sarcoma is a rare neoplasm of immune accessory cells. It occurs primarily in lymph nodes. Occurrences in the mediastinum are rarely reported. Diagnosis and management of follicular dendritic cell sarcoma remain unclear, and it is an under-recognized clinical entity. Only a few cases of paraneoplastic pemphigus as the first presentation of follicular dendritic cell sarcoma have been reported. We report an unusual case of follicular dendritic cell sarcoma of the anterior mediastinum, presenting as paraneoplastic pemphigus in a 62-year-old man. Typical histological features confirmed the diagnosis of follicular dendritic cell sarcoma, and surgical resection was successfully performed.

A rare case of pemphigus vegetans mimicking malignancy on F-18 FDG PET/CT.

A 42-year-old man with a history of chronic smoking and alcoholism was suspected to harbor a malignancy involving the perioral region and the scalp. He underwent an F-18 FDG PET/CT scan which revealed abnormal F-18 FDG accumulation in the oral mucosa and lips, extending to the nose, scalp, and bilateral cervical lymph nodes. Further work-up ultimately revealed the lesions to be secondary to pemphigus vegetans. Pemphigus vegetans is a rare variant of pemphigus vulgaris, an autoimmune bullous cutaneous disorder and involves mainly the flexural regions of the body. Unlike pemphigus vulgaris, lesions of pemphigus vegetans present as heaped up, eroded, and ulcerative plaques in the intertriginous regions of the body. Occasional lesions may be present on scalp and elsewhere in the Hallopeau variant of the disease. The use of F-18 FDG PET in the field of oncology is rapidly evolving; however, it is not tumor specific. The integration of CT into PET has increased the specificity of this modality. Nevertheless, there are many physiologic and benign conditions that may result in high accumulation of FDG, and may mimic malignancy. Familiarity with F-18 FDG-avid nonmalignant lesions may extend the use of F-18 FDG PET imaging beyond the field of oncology. To the best of our knowledge, this is the first description of PET/CT findings in pemphigus vegetans.

[Venous thromboembolism in a patient with noninvasive thymoma and a history of pemphigus]. / Zylna choroba zakrzepowo-zatorowa u pacjenta z nieinwazyjnym grasiczakiem i wieloletnia pecherzyca.

A case of a 69-year-old man, admitted due to an acute episode of venous thromboembolism (VTE) is described. He had a 3-year history of 'asymptomatic' (revealed on routine chest X-ray, but undiagnosed) tumor of anterior mediastinum, and a 8-year history of pemphigus vulgaris treated mainly with steroids. Three months following VTE episode he underwent tumor resection and histopathologic evaluation showed noninvasive, type AB thymoma. Gradual pemphigus remission started some weeks later. We analyse the relationship between thymoma, pemphigus and VTE, and emphasize the usefulness of echocardiographic thymoma imaging as a method complementary to computed tomography/magnetic resonance.