Category Archives: Clinical Research


Thymomas are relatively rare tumors. In this study, we investigated the clinical features of patients who underwent surgical resection for thymoma.


This study clinicopathologically evaluated 54 consecutive patients who underwent a surgical resection of thymoma in our department between 1994 and 2006.


A complete resection was performed in 52 patients, while two patients underwent an incomplete resection due to pleural dissemination. Combined resection with adjacent organs was performed for the lung (n=6), pericardium (n=5), and large vessels (brachiocephalic vein in three, superior vena cava in two). The concomitant autoimmune diseases were observed in 20 patients (37%), and they included myasthenia gravis in 17 patients, macroglobulinemia in one, pemphigus vulgaris in one, and stiff person syndrome in one patient. The histologic types of the World Health Organization classification diagnosed as type A in four patients, type AB in 14, type B1 in eight, type B2 in 15, and type B3 in 11. There were 27, 17, eight, and two patients with Masaoka stages I, II, III, and IV, respectively. Four patients died, and the causes of death included recurrence of thymoma in two, gastric carcinoma in one, and respiratory failure due to myasthenia gravis in one patient. The overall survival rate at 10 years was 94.6% in patients with stages I and II disease and 77.1% in patients with stages III and IV disease.


Long-term survival can be expected not only for patients at early stages, as well as for patients with stages III and IV disease if surgical resection is completed macroscopically.

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Erythema multiforme (EM) is an uncommon, immune-mediated disorder that presents with cutaneous or mucosal lesions or both. In herpes simplex virus (HSV)–associated EM, the findings are thought to result from cell-mediated immune reaction against viral antigen-positive cells that contain the HSV DNA polymerase gene (pol ). The target lesion, with concentric zones of color change, represents the characteristic cutaneous finding seen in this disorder. Although EM can be induced by various factors, HSV infection continues to be the most common inciting factor. Histopathologic testing and other laboratory investigations may be used to confirm the diagnosis of EM and to differentiate it from other clinical imitators. Imitators of EM include urticaria, Stevens-Johnson syndrome, fixed drug eruption, bullous pemphigoid, paraneoplastic pemphigus, Sweet’s syndrome, Rowell’s syndrome, polymorphus light eruption, and cutaneous small-vessel vasculitis. Because disease severity and mucosal involvement differ among patients, treatment should be tailored to each patient, with careful consideration of treatment risk vs benefit. Mild cutaneous involvement of EM can be managed primarily with a goal of achieving symptomatic improvement; however, patients with HSV-associated recurrent EM and idiopathic recurrent EM require treatment with antiviral prophylaxis. Inpatient hospitalization may be required for patients with severe mucosal involvement that causes poor oral intake and subsequent fluid and electrolyte imbalance. With this review, we strive to provide guidance to the practicing dermatologist in the evaluation and treatment of a patient with EM.

Neuromyelitis optica (NMO, also eponymously known as Devic’s disease) is an immune‐mediated demyelinating disease of the central nervous system that can lead to significant disability. Pediatric NMO is a rare disorder often reported after an infection. The authors report a 16year-old female patient with pemphigus foliaceus who developed subacute optic neuritis followed by cervical transverse myelitis. Restricted distribution of the lesions in the optic nerve and spinal cord was confirmed by ophthalmological evaluation and magnetic resonance imaging of the brain and spinal cord. She was started on intravenous methylprednisolone and then given a maintenance oral prednisone. Subsequently, she was treated with a nonsteroidal immunosuppressant, mycophenolate mofetil, with a target dose of 1000mg twice a day. Over the course of months, patient noted significant recovery of previous deficits and resolution of the cervical cord enhancement, expansion and cystic dilatation that was previously seen. This case is noteworthy for being the first patient reported with neuromyelitis optica associated with pemphigus foliaceus.



Herpes virus infections are well known infectious complications of pemphigus and bullous pemphigoid. We describe pathologic findings utilizing autopsy tissue from several organs from a patient affected by a new variant of endemic pemphigus in El Bagre, Colombia, South America.

We describe a patient by a new variant of endemic pemphigus foliaceus from El Bagre that was receiving high-dosage immunosuppressants when hospitalized and died suddenly following contact with a second patient affected by chicken pox.

We performed studies utilizing hematoxylin and eosin, immunohistochemistry, and direct immunofluorescence techniques on tissues from several organs.

We detected the presence of varicella zoster virus, as well as strong positivity for α-1 antitrypsin in the heart, kidneys, spleen, liver, skin, brain, lungs, pancreas, small and large intestines, and skeletal muscle. In regard to structural damage in the kidney and heart, we believe the observed damage is associated with the presence of autoantibodies to these organs, since both of them are rich in plakins and El Bagre-EPF patients present significant antibodies to plakin molecules.

In patients with endemic pemphigus foliaceus, we recommend complete isolation of the patient when receiving high dosages of systemic immunosuppressive agents. We further suggest the clinical possibility of a synergistic, fatal interaction between active pemphigus foliaceus, varicella zoster virus, herpes simplex virus, immunosuppressive agents, and a systemic activation of α-1 antitrypsin. Thus, we suggest adequate bed spacing, barrier nursing, and preventative testing for α-1 antitrypsin activation are warranted in these patients to address these complications.



Several studies have tried to determine the relationship between auto-antibodies against the acetylcholine receptor and the development of pemphigus vulgaris. In this study, we observed that antibody levels against the acetylcholine receptor are mildly elevated in pemphigus vulgaris (PV), and significantly correlate with disease severity on the initial diagnosis and during follow up. However, it is not clear if these antibodies are just an epiphenomenon or a potential trigger of the known pathogenic process in PV.



Background:  Pemphigus vulgaris (PV) is an autoimmune blistering skin disorder characterized by the presence of suprabasal acantholysis and autoantibodies against desmoglein 3. There are two different clinical forms: mucocutaneous (MCPV) or mucosal (MPV). However, it is not clear how PV lesions in oral, ear, nose and throat (OENT) areas produced by the very dynamic of the anatomical structures involved in the functions of the aerodigestive tract.

Objectives:  To investigate the pattern of OENT manifestations in PV, and their relationship with physiological traumatic mechanisms in stratified squamous epithelium structures.

Patients:  A prospective analysis of 40 patients diagnosed with MCPV (22 patients) or MPV (18 patients) was carried out in the University Clinic of Navarra. OENT manifestations were evaluated in all patients endoscopically. OENT involvement was divided into anatomical areas.

Results:  The most frequent symptom was pain, mainly on oral mucosa (87,5%). Buccal mucosa (90%), posterior wall of pharynx (67.5%), upper edge of epiglottis (85%) and nasal vestibule (70%) were the areas most frequently affected in the OENT mucosa. These localizations were related to physiological traumatic mechanisms in polystratified squamous epithelium structures.

Conclusions:  OENT endoscopy should be included in the examination of all PV patients. To know the most frequent localizations of active lesions on OENT mucosa in PV will help us to interpreter more efficiently the findings from OENT endoscopy. Also, information related to traumatic physiological mechanisms on OENT areas must be offered to patients in order to avoid the appearance of new active PV lesions.


Source: Study of Oral, Ear, Nose, and Throat Involvement…

Anti-p200 pemphigoid is a rare subepidermal blistering disease associated with autoantibodies against a 200kDa protein, reportedly corresponding to laminin γ1. However, direct evidence of the pathogenic potential of these antibodies is missing. We have followed up a patient with anti-p200 pemphigoid for five years. During this period she experienced a total of three generalised relapses. Quantifying our patient’s autoantibody concentrations against laminin γ1 by ELISA throughout the course of her disease we demonstrated a clear correlation with disease activity, thus providing first evidence of the possible pathogenic role of antibodies against laminin γ1 in anti-p200 pemphigoid. Further analysis by Western blotting revealed the occurrence of additional autoantibodies against α3 chain of laminin 332 1½ years after diagnosis, suggestive of intermolecular epitope spreading. Yet, the clinical appearance was unchanged and mucous membranes remained unaffected at any stage of the disease.;jsessionid=2CC44AEBB9086AAB7009C30B7627506C.d02t01


The 175 genes that were found to be significantly differentially expressed between cases and controls were used as input for pathway analysis with the ingenuity pathway analysis software. The network that was given the most significant P-value and the highest-scored functional pathways is shown. The network was found to be related to ST18 (marked in green). © 2012 Society for Investigative Dermatology

The recent buzz in the pemphigus and pemphigoid community stems from the publication of “Population-Specific Association between a Polymorphic Variant in ST18, Encoding a Pro-Apoptotic Molecule, and Pemphigus Vulgaris” in the Journal of Investigative Dermatology (available online, March 2012).

Despite the fact that pemphigus most often affects adults, it seems a large extent may be genetically determined. Indeed, the disease sometimes runs in families. Also, the deleterious antibodies implicated as a major cause of the disease can be found in healthy relatives of patients. And finally, the disease prevalence is highly population-dependent. For example, it is up to 40 times more common in Jewish as compared with non-Jewish populations.

The delineation of the genetic basis of a disease can reveal unknown aspects of its pathogenesis, which in turn is likely to point to novel therapeutic targets. To tackle the genetic basis of pemphigus vulgaris, Dr. Ofer Sarig and Eli Sprecher (Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel) led a collaboration with Ibrahim Saleh (co-Principle Investigator), Detlef Zilliekens, Michael Hertl and Markus M. Nöthen (Germany); Dedee Murrell (Australia), Aviv Barzilai, Henri Trau, Reuven Bergman, Ariel Darvasi, Karl Skorecki, Dan Geiger and Saharon Rosset (Israel).

Over the past two years, they assessed on a global (“genomic”) level the possibility that specific genetic variants may predispose to pemphigus vulgaris. They identified genetic variations in a gene called ST18 associated with the increased incidence of pemphigus vulgaris in Jewish and Egyptian patients. The fact that patients of German origin did not demonstrate the same trend suggests that the ST18 variants shows an increased risk for the disease in a population-specific manner. Carriers of the genetic changes have a 6-fold elevated risk of developing the disease. These genetic variations are associated with an increase in the expression of ST18 in the skin. Since ST18 is known to promote programmed cell death, increased expression of this protein may render the skin tissue more susceptible to the deleterious effects of the pathogenic antibodies.

Prof. Eli Sprecher is Director of Dermatology at The Tel Aviv Sourasky Medical Center in Israel.

What started as a posting of the story on Facebook quickly spread to the P/P Email Discussion Group where the talk turned to quicker diagnosis, better treatments, and a cure. Dr. Sprecher said, “The greatest reward for a physician involved in basic research like me is the feedback we get from our patients. This goes much deeper than anything else.” The P/P Community continues to be high-spirited and focused on researching this discovery and hopes more information is available at the IPPF’s Fifteenth Annual Meeting in Boston, May 18-20. 2012.

This step along the path of better understanding disease susceptibility and pathogenesis sheds new light on the genetic association of pemphigus vulgaris. Future work is still needed to more towards better genetic tools that impact disease management and targeted therapies.

But today, we are one step closer than we were yesterday.