Immune-Mediated Inner Ear Disease Associated with Type 1 Autoimmune Hepatitis: A Challenging Coexistence.

Autoimmune hepatitis (AIH) is characterized by elevated serum transaminase, increased immunoglobulin G levels, presence of autoantibodies, and hepatocellular damage. Coexistence with other autoimmune diseases has been reported in almost half of patients with AIH. Here, we report a 60-year-old man who developed rapidly progressive, bilateral, asymmetrical, and asynchronous sensorineural hearing loss that was consistent with immune-mediated inner ear disease (IMIED). This devastating presentation evolved as a late manifestation in the context of a six-month systemic illness that had previously resulted in type 1 AIH. A biochemical remission with normalization of aminotransferases achieved within two months after the initiation of corticosteroids with azathioprine. Further, an acceptable response has also been achieved at the patient regarding the right ear-hearing impairment; though, treatment could not reverse the substantial decrement in hearing capability of the left ear. To our knowledge, this is the first case report of the concurrent development of type 1 AIH and IMIED.

Rare Association of Hb D-Los Angeles (HBB: c.364G>C) with Hb H Disease: Diagnosis and Clinical Implications.

Hb D-Los Angeles (or Hb D-Punjab) (HBB: c.364G > C) is found worldwide and is derived from a point mutation in the ß-globin gene prevalent in the Punjab region of Northwestern India. Heterozygous or homozygous inheritance does not cause significant medical problems, whereas association with other hemoglobinopathies, especially ß-thalassemia (ß-thal) and sickle cell disease, changes the phenotype. Coinheritance of Hb D-Los Angeles with Hb H disease (α-/- -) has never been reported before. The presence of this rare combination in a family of Greek origin is herein described, and the challenges involving clinical management are discussed.

Immunohistochemical Study of Vasculogenic Mimicry and Angiogenesis in Melanocytic Tumors of the Eye and the Periocular Area.

BACKGROUND/AIM: The ability of a tumor to grow requires a sufficient blood supply. Microvascular density is considered the standard for assessing the neovasculature. Tumor cell vasculogenic mimicry refers to the formation of tumor cell-lined vessels that contribute to tumor neovascularization. The aim of the present work was to study angiogenesis and vasculogenic mimicry in benign and malignant melanocytic tumors of the eye and the periocular region. PATIENTS AND METHODS: Histological sections from 118 patients were studied. Eighty-eight of the patients had nevi while the remaining 30 had malignant melanomas. Microvascular density was assessed by using antibodies against the endothelial cell markers CD31 and CD34. Vascular-like channels between neoplastic cells, that were not lined by endothelial cells and thus were negative for CD31 and CD34, represented areas of vasculogenic mimicry. RESULTS: Angiogenesis was more pronounced in melanomas compared to melanocytic nevi and was increased in melanomas with high mitotic index and/or epithelioid cell preponderance compared to melanomas with low mitotic index and/or spindle cell predominance. Vasculogenic mimicry was observed in many melanomas, while it was evident in the minority of benign nevi as well. CONCLUSION: The existence of vasculogenic mimicry in benign nevi might have prognostic implications.

Telogen effluvium as the first symptom of Crohn's disease in a child.

Crohn's disease usually manifests gastrointestinal symptoms, however in some cases the patient presents with prominent or even exclusive extraintestinal involvement. Alopecia has been reported as a complication of therapeutic agents used in the treatment of inflammatory bowel disease, and, in a few cases of adult patients, prior to the appearance of gastrointestinal symptoms. We present a 10 year-old-child with telogen effluvium that appeared one year before the diagnosis of Crohn's disease, as the first and only symptom at that time. Other systemic causes of hair loss such as micronutrient deficiencies, endocrine imbalance or chemical exposure were excluded. Eight months later the patient presented with mild iron deficiency and signs of social retraction, while two months before the final diagnosis of Crohn's disease other more characteristic alarming symptoms (mild fever, oral apthous ulcers, weight loss) were added to the clinical picture. Alopecia improved after remission of Crohn's disease, reappeared when the patient relapsed, and finally resolved gradually when complete remission of Crohn's disease was achieved. Telogen effluvium was the first symptom of Crohn's disease in a child, and, although this is a rare association, it should be considered as an extraintestinal manifestation of Crohn's disease.

Synthetic antimalarial drugs and the triggering of psoriasis - do we need disease-specific guidelines for the management of patients with psoriasis at risk of malaria?

BACKGROUND: Α distinct side effect of the synthetic quinolinic antimalarial drugs, still widely used for the treatment and prophylaxis of malaria, is the induction of psoriasis in predisposed or susceptible individuals. OBJECTIVE: To describe two patients that had induction and exacerbation of psoriasis due to the administration of hydroxychloroquine, to adapt pertinent literature on the pathophysiology of this side effect, to review psoriasis-triggered cases by newer, non-quinolinic antimalarials, and to propose malaria treatment and prophylaxis guidelines for psoriatic patients. PATIENTS AND METHODS: Two patients, a 40-year-old female with unknown history of psoriasis and a 37-year-old primigravida with an established history of psoriasis, were treated with hydroxychloroquine for a newly diagnosed lichen planopilaris and for an exacerbation of psoriatic arthritis, respectively. PubMed was searched (last accessed 20 October 2012) employing as search strategy the keywords (psoriasis) AND (drug), where "drug" is the name of each of the newer, non-quinolinic antimalarials. RESULTS: Psoriasis was controlled in both patients. The primigravida gave birth to a healthy child at 39 weeks of gestation. The literature review returned no articles that linked the newer antimalarials with psoriasis. CONCLUSION: Despite the increased awareness, antimalarials-triggered psoriasis is still diagnosed. Fortunately, the current artemisinin-based antimalarial treatment can be safely offered to susceptible individuals. Additionally, prophylaxis with doxycycline or the combination atovaquone-proguanil could be a safe suggestion for malaria prophylaxis in psoriatic patients.

Squamous cell papilloma of the conjunctiva due to human papillomavirus (HPV): presentation of two cases and review of literature.

PURPOSE: We describe two patients with squamous cell papilloma of the conjunctiva due to human papilloma virus (HPV) and review the literature. PATIENTS AND METHODS: Two patients with conjunctival tumors were examined and treated in the University Eye Clinic and diagnosed in the University Pathology Department, University Hospital of Ioannina, Greece. The first patient was a 48-year-old man presenting with an extended papillomatous lesion in bulbar conjunctiva covering part of the cornea of his right eye. The second patient was a 24-year-old man presenting with a polypoidal papillomatous lesion on the caruncle of his right eye. The two lesions were removed surgically, cryotherapy was applied to the adjacent conjunctiva, and topical mitomycin-C was used. The amniotic membrane was used to restore the conjunctival defect in the first patient. The two removed lesions were sent to the Pathology Department for histopathological examination. Immunohistochemistry, DNA in situ hybridization, and polymerase chain reaction (PCR) analysis were performed. RESULTS: In the first patient, histopathology showed the presence of a benign squamous papilloma with koilocytosis. DNA in situ hybridization with broad-spectrum probes showed that this patient was positive for HPV DNA. In the second patient, histopathology showed the presence of a squamous papilloma with mild dysplasia and koilocytosis. Immunohistochemical analysis was positive for HPV protein and p16 protein. DNA in situ hybridization with broad-spectrum probes showed that the patient was positive for HPV DNA. PCR analysis showed the presence of HPV 6. According to morphological and molecular findings, both patients were diagnosed with squamous cell papilloma due to HPV. CONCLUSION: HPV can infect the ocular surface. According to clinical results, the ophthalmologist in cooperation with the pathologist can recommend appropriate laboratory examinations to confirm the diagnosis and successfully treat conjunctival papillomas.

Chronic periaortitis (retroperitoneal fibrosis) concurrent with recurrent cutaneous eosinophilic vasculitis.

Chronic periaortitis (CP) is usually accompanied by at least mild manifestations of systemic autoimmunity; however, skin manifestations are rare. Here, we report an 82-year-old woman presenting with a pruritic annular eosinophilic dermatosis that led to the diagnosis of recurrent cutaneous eosinophilic vasculitis (RCEV) coexisting with a latent CP. The present paper is reminder that a CP should be included as a potential differential diagnosis in the elaboration of patients with cutaneous vasculitis that is suspicious of underlying autoimmunity.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) in a child, associated with a rotavirus infection: a case report.

INTRODUCTION: Sweet's syndrome characterized by fever, blood neutrophilia and inflammatory skin lesions, is rarely diagnosed in children. It presents in three clinical settings: classical Sweet's syndrome, usually after a respiratory tract infection; malignancy-associated, frequently related to acute myelogeneous leukemia; and drug-induced. We present, to the best of our knowledge, the first case of a rotavirus -infection-related Sweet's syndrome. CASE PRESENTATION: An 18-month-old boy of Hellenic origin was referred to us with diarrhea, fever, neutrophilia, typical skin lesions, asymmetrical hip arthritis and oropharyngeal involvement. A skin biopsy confirmed the diagnosis. Thorough screening did not reveal any underlying systemic illness, except for the confirmation of an overt rotavirus infection. The syndrome responded promptly upon corticosteroid administration; no recurrence was observed. CONCLUSION: Besides describing the connection of Sweet's syndrome to a rotavirus infection, this case report is also a reminder that in a child presenting with a febrile papulo-nodular rash with neutrophilia Sweet's syndrome should be included in the differential.

Periocular xanthogranuloma: A forgotten entity?

Periocular xanthogranulomatous diseases are a rare group of disorders which are characterized by a predilection to affect the orbit and ocular adnexa and special histopathological features, in particular infiltrates comprising non-Langerhans-derived foamy histiocytes and Touton giant cells. The differential diagnosis is difficult and occasionally definite diagnosis cannot be established even after clinical and histopathological findings are taken together. We describe a case of a middle-aged man who presented with a 10-year history of voluminous eyelid swelling with concomitant late-onset atopic manifestations, namely bronchial asthma and allergic rhinitis with nasal polyps. After thorough clinical and laboratory investigation, including a biopsy of the eyelid, we classified the patient's disease to a rare entity that has been relatively recently described: periocular xanthogranuloma associated with adult-onset asthma. In a review of the literature, no prospective trials concerning the treatment of this disease were found. The literature mainly contained case reports and case series in which corticosteroids and chemotherapy with alkylating agents have been reported to be beneficial. We treated our patient with a combination of oral corticosteroids and cyclophosphamide pulses and we observed substantial regression of the eyelid masses together with a normalization of systemic immunologic abnormalities.

Primary cutaneous leiomyosarcoma: clinicopathological analysis of 36 cases.

AIMS: Cutaneous leiomyosarcomas (LMS) are rare in comparison with their deep-seated soft tissue and uterine counterparts, and have been poorly characterized. The aim was to verify whether the clinical behaviour of purely dermal LMS is different from that of LMS with minimal subcutis invasion. METHODS AND RESULTS: Twenty-one purely dermal LMS and 15 dermal LMS with minimal subcutis extension were analysed. Tumours developed in 27 men and nine women (age range 29-91 years); most tumours showed a fasciculated (n = 23), pilar-type (n = 12) and pleomorphic (n = 1) pattern. During the follow-up period (range 2-192, mean 41 months) recurrences occurred in 1/16 (6.2%) of tumours confined to the dermis and in 2/11 (18.1%) tumours with minimal subcutis extension. The three recurrent tumours were high-grade LMS, two of which exhibited myxoid areas. One patient with a pleomorphic dermal LMS with minimal extension into fat developed distant metastases 15 years after diagnosis. CONCLUSIONS: For LMS involving the skin, it is advisable to recognize and indicate in the histopathology report the depth of dermal and/or subcutaneous extension, since even minimal subcutaneous involvement may be associated with late local recurrences and/or distant metastases, and therefore appropriate and long-term follow-up is needed.

Expression of Notch-1 and alteration of the E-cadherin/beta-catenin cell adhesion complex are observed in primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma).

Increasing evidence indicates that Notch signaling contributes to physiological processes, including development and differentiation, as well as tumorigenesis, either as a tumor promoter or suppressor, depending on cellular context, expression levels and cross talk with other signaling systems. Recent studies reported absent or minimal Notch-1 expression in neuroendocrine tumors of the lung and gastrointestinal tract, suggesting a tumor-suppressor function of Notch-1. Merkel cell carcinoma is a rare and highly aggressive primary cutaneous neuroendocrine carcinoma. Because no information is available on Notch-1 expression in this tumor, we have investigated a series of 31 Merkel cell carcinoma for Notch-1 immunoreactivity. Immunoreactivities for E-cadherin and beta-catenin were also analyzed. All but 1 Merkel cell carcinoma (30 of 31) retained cytoplasmic and membrane Notch-1 expression in more than 50% of cells. beta-Catenin displayed a prevalent membrane-associated staining in 30 of 31 cases, and 22 cases showed more than 50% of immunoreactive cells whereas nuclear beta-catenin was seen only in 2 of 31 cases. E-cadherin membranous expression was remarkably low, as only 1 of 26 cases was found positive in more than 50% of cells. In contrast with neuroendocrine tumors in other tissues, evident Notch-1 expression was found in Merkel cell carcinoma. This finding does not support a tumor-suppressor function of Notch-1 in Merkel cell carcinoma. Downregulation of E-cadherin and diffuse membranous beta-catenin expression suggest a dysregulation of the E-cadherin/beta-catenin complex in Merkel cell carcinoma. This may contribute to local invasion and distant metastasis.

Febrile "migrating" eosinophilic cellulitis with hepatosplenomegaly: adult toxocariasis - a case report.

BACKGROUND: Eosinophilic cellulitis (Wells' syndrome) is a polyetiologic clinical entity with still obscure pathogenesis. Clinically overt toxocariasis is uncommon in adults, yet helminthozoonoses, including toxocariasis have been occasionally implicated in the pathogenesis of eosinophilic cellulitis. CASE REPRESENTATION: A 55-year-old female patient presented with a skin biopsy verified recurring febrile eosinophilic cellulitis, blood eosinophilia (42%), slight anaemia (Hct 35%), hepatosplenomegaly and positive specific anti-Toxocara canis antibodies. Toxocariasis-associated eosinophilic cellulitis was diagnosed. Already two weeks after treatment with thiabendazole the skin lesions resolved, T. canis antibody titre normalized eight months after treatment and no recurrences of eosinophilic cellulitis have been observed (for meanwhile three years). CONCLUSION: The clinical characteristics (relapsing skin lesions, fever, hepatosplenomegaly), the laboratory features (blood eosinophilia, modest anemia, positive T. canis serology) and the clinical course after treatment, all support a causal relationship between Toxocara infection and the disease of this patient. We propose that in this context eosinophilic cellulitis must be interpreted as the leading symptom of a "skin-predominant" form of overt adult toxocariasis out of a spectrum of toxocariasis-associated febrile, "migrating-relapsing", organotropic eosinophilic inflammatory syndromes.

Plexiform neurofibroma of the cauda equina: a case report and review of the literature.

Plexiform neurofibroma of the cauda equina is extremely rare. Herein, a case is reported in a 56-year-old man who also had muscle atrophy, severe motor disturbance, and mild sensory disturbance of the left leg due to childhood poliomyelitis. The clinical symptoms manifested insidiously until the patient developed cauda equina syndrome. At operation, the tumor mass was observed to engulf the nerve roots of the cauda equina. After pathological examination, the diagnosis of plexiform neurofibroma was made. Neither the patient described herein nor any previously reported patients had neurofibromatosis.