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Dupilumab is an anti-interleukin-4 receptor monoclonal antibody that was recently approved for the treatment of atopic dermatitis (AD). In this single-center retrospective study, clinical baseline data of 117 severe AD patients treated with dupilumab were collected. At baseline and at weeks 4 and 16, disease severity was assessed through the Eczema Area and Severity Index (EASI) and quality of life through the Dermatology Life Quality Index (DLQI) questionnaire, Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), Peak Pruritus Numerical Rating Scale (NRS-itch), and VAS-sleep. Response to dupilumab was defined as an improvement of ≥75% in EASI from baseline (EASI75). At multivariate analysis, AD onset before 18 years [OR, 2.9; 95% CI, 1.2-7.2; p = 0.0207] and absence of hypereosinophilia [OR, 2.24; 95% CI, 1.03-4.86; p = 0.0412] were identified as significant predictive parameters for response to dupilumab in terms of EASI75 at week 4 but not at week 16. Significant reductions in EASI, DLQI, POEM, HADS, NRS-itch, and VAS-sleep were found between week 4 versus baseline ( p < 0.0001 for all) and week 16 versus baseline ( p < 0.0001 for all). Early AD onset and absence of hypereosinophilia may be suggested as predictive markers of early response to dupilumab. We confirmed the efficacy and safety of this agent along with the improvement of life quality in severe AD patients.

Omalizumab is approved for use in chronic spontaneous urticaria (CSU); however, it is not approved for chronic inducible urticaria (CIndU). The aim of the present study was to assess the effectiveness of omalizumab in treating CSU and CIndU in Italy. This is a multicentre prospective observational real-life study involving patients with severe urticaria capable of undergoing omalizumab therapy. We enrolled 127 patients (59.1% females), ranging in age from 15 to 83 years, 69.3% had CSU alone, 26.8% had CSU and CIndU, and 3.9% had only CIndU (30.8% delayed pressure, 35.9% dermographic, 15.3% cholinergic, 12.8% cold, 5.1% aquagenic). After the first cycle of omalizumab (300 mg every 4 weeks for 24 weeks), 16 CSU patients and 10 patients (20.5%) with CIndU with or without CSU did not require a second cycle of omalizumab (300 mg every 4 weeks for 20 weeks). The patient with aquagenic urticaria achieved remission after the first cycle. None showed a lack of response to the second cycle of omalizumab. Omalizumab is a promising drug for both spontaneous and inducible chronic urticaria. Current evidence indicates that omalizumab may be approved also for CIndU., (© 2018 S. Karger AG, Basel.)

Omalizumab is very effective in the majority of patients with severe chronic spontaneous urticaria (CSU), but its mechanism of action is still unclear. In CSU the coagulation cascade is activated with an intensity that parallels the disease severity, and elevated plasma D-dimer levels are associated with a poor response to both antihistamines and cyclosporin. We measured D-dimer plasma levels before and after the first administration of omalizumab in 32 patients with severe CSU. A number of clinical and laboratory parameters were recorded, including the urticaria activity score, presence of angioedema, disease duration, C-reactive protein, anti-nuclear, and anti-thyroid antibodies. Baseline D-dimer levels were elevated in 19 (59%) cases. Omalizumab induced a complete response in 25 patients (78%), in most cases already after the first administration. At baseline, 14/25 responders had increased D-dimer plasma levels versus 5/7 non-responders. All responders showed a dramatic decrease of D-dimer plasma levels after the first administration of the drug (from 1,024 ± 248 [mean ± SE] to 251 ± 30 ng/mL; p = 0.003). In contrast, non-responders did not show any reduction in D-dimer levels after omalizumab administration (from 787 ± 206 to 1,230 ± 429 ng/mL; p = ns). In conclusion, plasma levels of D-dimer are frequently elevated in patients with severe CSU before omalizumab administration and decrease according to the clinical response of the disease to the drug, suggesting a possible effect of omalizumab on coagulation activation and fibrin degradation in a subset of CSU patients., (© 2017 S. Karger AG, Basel.)

Contact (allergic) dermatitis is a skin disorder related to natural exposure to various allergens. Systemic contact dermatitis (SCD) describes a cutaneous eruption in response to systemic exposure to an allergen. The exact pathologic mechanism remains uncertain. Herein we describe a 36-year-old woman with symmetric systemic allergic contact dermatitis, unresponsive to conventional treatment, associated with dental alloy-contact hypersensitivity. We did skin patch testing and the blood lymphocyte transformation test (LTT) from the dental allergen series to assess contact allergy to restorative dental materials. On patch testing, positive allergic contact dermatitis reactions to metals occurred (nickel, potassium dichromate, and gold). Nickel hypersensitivity was confirmed by LTT, which also revealed silver-amalgam sensitization. Our case report highlights the need to consider adverse reactions to base-metal dental alloys in the differential diagnosis of cases of systemic allergic contact dermatitis.

A 68-year-old Caucasian man with a remote history of daily colloidal silver ingestion presented for ophthalmic examination in which he was noted to have a distinct slate gray skin discoloration. Funduscopy revealed confluent perimacular drusenoid deposits bilaterally, most of which localized at the level of or anterior to the inner segment ellipsoid band by optical coherence tomography (OCT) imaging. Enhanced depth imaging OCT demonstrated marked choroidal thinning. Fluorescein angiogram displayed a dark or silent choroid. Confirmatory serum silver levels were found to be markedly elevated. This report describes a unique geographic maculopathy with large drusenoid deposits anterior to the ellipsoid layer and severe choroidal thinning in association with ocular argyrosis., (Copyright 2013, SLACK Incorporated.)

Background: The advent of anti-vascular endothelial growth factor (VEGF) treatment for choroidal neovascularization has become the standard of care for wet age-related macular degeneration (AMD). Among the choices, intravitreal bevacizumab, for off-label use, has gained popularity. Recent attention has been on the complications of anti-VEGF treatment, one of them being a retinal pigment epithelial (RPE) tear. A tear in the RPE is a visually devastating complication, most commonly associated with fibrovascular pigment epithelial detachments (PED) in AMD, and may develop during the course of intravitreal bevacizumab treatment., Case Report: We report a case of an 85-year-old white man with decreased visual acuities of 20/70 in the right eye (O.D.) and 20/150 in the left eye (O.S.) secondary to dry AMD O.D. and wet AMD with a fibrovascular PED O.S. The patient underwent treatment with an intravitreal bevacizumab injection O.S. Six weeks after the initial injection, the patient returned with further declining vision in the left eye secondary to an RPE tear., Conclusion: Intravitreal bevacizumab has proven to be an effective treatment for choroidal neovascularization and shows a significant improvement of vision for wet AMD patients. However, there are risks associated with the procedure. One of the most visually significant is an RPE tear, which can occur at an incidence rate as high as 17%. Optometrists should be aware of this rare, but serious, complication associated with anti-VEGF treatment for wet AMD., (Published by Elsevier Inc.)

Aim: Sclerodermus domesticus is an insect belonging to the order Hymenoptera. Female of S. domesticus feeds on larvae of xylophagous Coleoptera and Lepidoptera living in the galleries they dig in old wooden furniture. Human infestation is rare., Methods: In the last few months, we observed nine adult patients (7 males and 2 females) who were affected by S. domesticus infestation. Seven patients were antiquarians or restorers and two were housewives. The rash was characterized by erythematous-papular lesions, accompanied by pruritus and/or pain. In addition, 7 patients reported general malaise and fever. In all cases it was possible to find specimens of S. domesticus in furniture or house dust., Results: Complete remission was obtained with topical corticosteroids, oral anti-histamines and pest control of furniture., Conclusion: Antiquarians and restorers and, in general, the people in close contact with furniture infested by S. domesticus may be stung by these insects. S. domesticus infestation can therefore be considered as an occupational disease in these subjects.

Background: Retinal astrocytic hamartomas are glial tumors of the retinal nerve fiber layer that arise from retinal astrocytes. Classically they appear as a cream-white, well-circumscribed, elevated lesion that may present as multiple or solitary sites. A lesion is commonly seen with a multilobulated, "mulberry" appearance, but can also appear flat and semitranslucent. It is most frequently associated with tuberous sclerosis (TS) but may also be found rarely in patients with neurofibromatosis. Although the finding may point toward a systemic association, it can also be found incidentally on retinal examination as an isolated presentation., Case Reports: Two cases of solitary retinal astrocytic hamartomas without systemic complications discovered at routine examination are presented. Both patients were found to have a raised, multilobulated retinal lesion consistent with the appearance of a retinal astrocytic hamartoma. In both cases, the patients had no personal or family history of seizures or any signs of unusual dermatologic lesions. B-scan ultrasonography, fluorescein angiography, and magnetic resonance imaging (MRI) were performed as necessary., Conclusion: A retinal astrocytic hamartoma is typically associated with TS but can also present as a spontaneous, idiopathic lesion. Prompt referral to rule out TS or other systemic associations, particularly in young children, is important. Neuroimaging, along with other diagnostic tests, may ensure the proper management and rule out need for further evaluation. Spontaneous lesions without systemic association can initially be monitored closely to rule out possible progression. Once stability has been established, annual follow-up with a primary care eye practitioner is appropriate., (Published by Elsevier Inc.)

The link between human herpesvirus 8 (KSHV) and Kaposi's sarcoma (KS) has been proven, but many important aspects including risk factors, genetic predisposition to tumor development, transmission of KSHV, and the pathogenic potential of different genotypes remain to be elucidated. Possible associations between clinical parameters and antibody levels, viral load fluctuations, and viral genotype were analyzed by quantitative real-time PCR, an in-house developed IFA assay, and sequence analysis of ORF K1-VR1 in blood, serum and saliva of 38 subjects with classic KS (cKS). KSHV lytic antibodies were significantly increased in stage IV compared to stage I and II patients (p = 0.006 and p = 0.041, respectively). KSHV blood, serum, and saliva viral load was comparable in all stages. The highest viral loads were detected in saliva, and they decreased in stages III-IV compared to stages I-II patients. Higher concentrations of lytic antibodies and higher viral loads were observed in fast progressing cKS patients, in whom KSHV detection from blood was also more frequent. Type A KSHV strain was almost exclusively present in rapid progressors (12/17 cases), while C type was mainly present in slow progressing patients (6/7 cases). Finally, detection of type A KSHV strain associated with higher blood viral loads. KSHV lytic antibody levels and viral load can be used to monitor clinical evolution of cKS. Infection supported by KSHV A subtype is associated with more rapid progressive disease. Careful monitoring and aggressive therapeutic protocols should be considered in patients with KSHV A-supported infection.

Lymphedema of the lower extremities is a frequent complication of Kaposi's sarcoma (KS). Compressive therapy is the basis of treatment for lymphatic disorders, but to the authors' knowledge, there are no controlled trials to evaluate its effectiveness in KS-related lymphedema. Sixty-five patients with classic KS-associated lymphedema limited to below the knee were studied. Fifty patients received below-knee elastic stockings, whereas the remaining 15 did not use any compressive device. Among treated patients, 60% (30/50) experienced a limb volume reduction, while 40% (20/50) had an increase of limb volume. In contrast, all patients (15/15) of the untreated group had an increase of limb volume. No correlation between lymphedema reduction and systemic or local chemotherapy was observed, supporting compressive therapy as the major strategy for the treatment of this condition. Our results suggest that elastic stockings may be important tools for the management of lymphedema associated to classic KS.

In this study, we investigated whether dendritic cells (DCs) are altered in classic Kaposi's sarcoma (cKS), a lympho-angioproliferative disorder associated with human herpesvirus-8 (HHV-8) infection. By direct analysis of peripheral blood DCs (PBDCs), we demonstrated that cKS patients have lower frequency of myeloid and plasmacytoid DCs than controls. This reduction was greater in patients with advanced stages of disease. PBDCs from cKS patients also showed up-regulated expression of the scavenger receptor CD91 and impaired IL-12 expression. PB monocytes that represent DC precursors in vivo and in vitro showed the same alterations; accordingly, DCs differentiated in vitro from cKS monocytes were similarly affected. The same alterations were induced by addition of cKS plasma during DC differentiation from control monocytes. These results indicate that PBDCs and their precursors are altered in cKS and suggest that soluble circulating factors participate in this process. The study may provide new insights into the pathogenesis of cKS.

Classic Kaposi's sarcoma (CKS) is a multifocal vascular mesenchymal tumour of unknown origin. Human herpesvirus 8 (HHV8) is now considered to be strongly involved, as a necessary co-factor, though insufficient for development of the disease. Additional identified risk factors include environmental factors, personal habits and genetic susceptibility, with different loci suspected of being risk factors for CKS. Since various human leukocyte antigen (HLA) patterns have been suggested as potential host-related co-factors, the distribution of these alleles was studied in 41 CKS patients, 285 geographically-matched healthy controls (HC) and 17 HHV8-positive controls. Molecular typing of HLA was performed using the polymerase chain reaction sequence-specific primer method (SSP-PCR). Frequency distribution was evaluated by the Chi-squared test with Yates' correction. Odds ratios (OR) and respective 95% confidence limits (CI) were calculated. A significantly higher frequency of HLA-DRB1*13 was observed among the CKS patients (20.7%) compared to the HC (9.8%) (p<0.01; OR: 2.32; 95%CI: 1.21-4.41). Overall, these results indicated that HLA-DRB1*13 may play a role in the development of CKS, while HLA-DQB1*0604 allele involvement occurs in linkage disequilibrium with HLA-DRB1*13. To our knowledge, this is the first study documenting an HLA-DRB1 and -DQB1 loci association with CKS development in the mainland Italian population., (Copyright© 2006 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved.)

Background: Primary acquired melanosis (PAM) presents as a unilateral patchy area of conjunctival pigmentation mostly found in middle-aged or elderly white patients. Because PAM has the potential of becoming malignant, it is important to recognize PAM and to rule out other causes of pigmented lesions. The presence or absence of atypia is helpful in determining the potential for malignancy, because PAM without atypia is usually benign, whereas PAM with atypia may convert into a conjunctival melanoma. If atypia is present, the presence or absence of epithelioid cells and the pattern of intraepithelial growth are the main factors in determining the likelihood of neoplastic transformation. However, atypia can only be determined with histopathologic examination. Therefore, a biopsy is usually recommended., Case Report: A 72-year-old white man presented for his annual examination with no visual complaints. His ocular history was remarkable for early cataracts and for a choroidal nevus. Slit lamp examination found a large dark area of elevated conjunctival pigmentation at the medial canthus that extended onto the superior bulbar conjunctiva and superior palpebral conjunctiva in the left eye. No conjunctival pigmentation had been noted previously. Results of a biopsy indicated primary acquired melanosis with atypia. The lesion was surgically excised, and the conjunctiva was reconstructed with an amniotic membrane graft. The patient was subsequently treated with topical 5-fluorouracil chemotherapy. There have been no signs of recurrence to date after his treatment., Conclusion: Because of the potential for malignancy, biopsies of all cases of primary acquired melanosis are indicated. If atypia is present, treatment options include local excision, cryotherapy, and topical chemotherapy.

Background: Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a condition that presents classically as bilateral, symmetrical, grayish-yellow, round or oval-shaped lesions within the macular area. These lesions are mildly elevated and are typically one third to one half disc diameter in size. The onset of the disease is usually between 30 and 50 years of age with variable genetic inheritance, although some have suggested an autosomal dominance inheritance pattern. Patients with AOFVD typically present with symptoms of blurred vision or mild metamorphopsia. Results of diagnostic testing show a normal or mildly subnormal electro-oculogram (EOG). Fluorescein angiography results (FA) typically show hypofluorescence in the area corresponding to the vitelliform lesion and a surrounding ring of hyperfluorescence. Results of optical coherence tomography (OCT) show the vitelliform lesion as being located in the retinal pigment epithelium (RPE) layer or between the RPE and photoreceptor layer., Case Reports: Two cases of AOFVD are presented with each patient having different macular appearances owing to the different stage of the disease process. In case 1, a 76-year-old white man presented with stage II AOFVD characterized by typical vitelliform lesions. His best-corrected acuities were 20/70+ in the right eye (O.D.) and 20/80- in the left eye (O.S.). In case 2, a 54-year-old white man presented with stage V AOFVD with bilateral atrophic maculae with best-corrected acuities of 10/60- O.D. and 10/160- O.S., Conclusion: Patients with adult-onset foveomacular vitelliform dystrophy typically have slow progressive vision loss. However, patients can develop dramatically decreased vision owing to subfoveal choroidal neovascularization (CNV). Thus, it is important to establish the correct diagnosis and monitor this condition. Furthermore, because there are reports of AOFVD having an autosomal dominance inheritance pattern with variable penetrance, it is recommended that the patient's family members have a comprehensive eye examination to rule out any early signs of this rare eye condition.

Background: Cytomegalovirus (CMV) retinitis was a much-feared visual complication of late-stage acquired immunodeficiency syndrome (AIDS) in the past. Its incidence has waned significantly owing to the benefits of potent antiretroviral combination therapy, which for many individuals has provided some degree of immune reconstitution and avoidance of opportunistic infections, particularly this blinding disease., Case Report: A 45-year-old white man with long-standing, multidrug-resistant human immunodeficiency virus (HIV) infection and severe immunodeficiency despite multiple antiretroviral drug regimens, presented to the eye clinic reporting decreased vision and spider web patterns in his left eye for the past week. Best-corrected visual acuity was 20/20 in the right (O.D.) and 20/25 in the left eye (O.S.). Dilated funduscopic examination of the left eye found vasculitis of the midperipheral inferonasal arcade in the midperiphery, with surrounding intraretinal hemorrhage and granular retinal necrosis. Diagnosis of cytomegalovirus retinitis was made, and the patient began induction therapy with oral valganciclovir 900 mg twice a day for 3 weeks. Maintenance therapy after retinitis stabilization was 900 mg every day until any observed recurrence of infection. Three months after complete resolution of the active retinitis, the patient returned to the clinic reporting new floaters of recent onset. A reactivation of the CMV retinitis warranted a reinduction with valganciclovir 900 mg orally twice a day for 3 weeks., Conclusion: This case is illustrative of the efficacy and relative ease of administration of valganciclovir, the newest medication approved for treatment and maintenance of CMV retinitis. Despite his severe immunodeficiency, our patient tolerated the induction and maintenance therapy of oral valganciclovir well, and the CMV retinitis was stabilized and resolved with full recovery of visual acuity.

Background: Retinitis pigmentosa (RP) is one of the most common hereditary retinal dystrophies and causes of visual impairment affecting all age groups. The reported incidence varies, but is considered to be between 1 in 3,000 to 1 in 7,000. Sector retinitis pigmentosa is an atypical form of RP that is characterized by regionalized areas of bone spicule pigmentation, usually in the inferior quadrants of the retina., Case Report: A 57-year-old Hispanic man with a history of previously diagnosed retinitis pigmentosa came to the clinic with a longstanding symptom of decreased vision at night. Bone spicule pigmentation was found in the nasal and inferior quadrants in each eye. He demonstrated superior and temporal visual-field loss corresponding to the areas of the affected retina. Clinical measurements of visual-field loss, best-corrected visual acuity, and ophthalmoscopic appearance have remained stable during the five years the patient has been followed., Discussion: Sector retinitis pigmentosa is an atypical form of RP that is characterized by bilateral pigmentary retinopathy, usually isolated to the inferior quadrants. The remainder of the retina appears clinically normal, although studies have found functional abnormalities in these areas as well. Sector RP is generally considered a stationary to slowly progressive disease, with subnormal electro-retinogram findings and visual-field defects corresponding to the involved retinal sectors., Conclusion: Management of RP is very difficult because there are no proven methods of treatment. Studies have shown 15,000 IU of vitamin A palmitate per day may slow the progression, though this result is controversial. Low vision rehabilitation, long wavelength pass filters, and pedigree counseling remain the mainstay of management.

Background: Meningiomas involving the tuberculum sellae and planum sphenoidale typically cause visual loss by affecting the optic nerve and anterior chiasm. We present a case of a tuberculum sellae meningioma concurrent with lymphomatoid papulosis, a T-cell lymphomatoid skin disorder., Case Report: A 50-year-old black woman came to the eye clinic with a symptom of decreased vision in the right eye for one week, especially when reading. Best-corrected vision was counting fingers at two feet O.D. and 20/40 O.S. She was seen seven months earlier, with 20/25 O.D. and O.S. Dilated fundus examination revealed bilateral optic atrophy, O.D. greater than O.S. MRI revealed a meningioma arising from the tuberculum sellae and planum sphenoidale region. The meningioma was partially resected nine days later Visual field performed 18 days postoperatively demonstrated an overall depression in the right eye and no defect in the left eye. Best-corrected vision improved to 20/150 O.D. and 20/30 O.S., Conclusion: Meningiomas are generally benign tumors that can cause symptoms if vital structures are compromised. Altered visual function and optic atrophy may be the only presentation of intracranial and orbital tumors. Intracranial meningiomas may be associated with systemic conditions that can infiltrate the optic nerve, including lymphocytic disorders. Lymphomatoid papulosis (LyP) is a rare cutaneous disorder involving infiltrating clonal T-cells that has been associated with disseminated lymphomatic skin tumors. It is unclear if there is a direct association between LyP and meningiomas.

Background: Idiopathic sclerochoroidal calcification (ISC) is an uncommon condition of calcium deposition at the level of the sclera and choroid of the posterior pole. With normal acuity and visual field, it typically manifests in asymptomatic older males. It can be diagnosed on clinical grounds, appearing as multiple geographic, yellowish, placoid-like lesions in the sclera and choroid, commonly found in the superotemporal arcade of the midperipheral fundus in both eyes. Ocular ultrasound and fluorescein angiography have classic results., Case Report: An 85-year-old white man came to us for routine examination. Best-corrected visual acuity was 20/40 O.D. and O.S. Dilated fundus examination revealed several midperipheral yellowish-white deposits with retinal pigment epithelium hyperpigmentation temporally in each eye. Ocular ultrasound revealed high reflectivity consistent with calcium. The lesions demonstrated mild hyperfluorescence in the late phase of fluorescein angiography. Laboratory testing was void of abnormal calcium or phosphorous metabolism, and a diagnosis of ISC was made., Conclusion: Idiopathic sclerochoroidal calcification is a benign lesion of calcium deposition in the posterior pole, often discovered on routine examination. Although it is idiopathic, systemic evaluation is warranted to rule out dystrophic or metastatic calcification by various pathological conditions associated with abnormal calcium-phosphorus metabolism--most notably, hyperparathyroidism. Differential diagnoses include choroidal osteoma, melanoma, and metastatic carcinoma.

Aim: Kaposi's sarcoma (KS) is a lympho-angioproliferative disorder characterized by angiomatous nodules and plaques that mainly affect the skin. The disease is consistently associated with human herpesvirus-8 (HHV8) and with a state of preexistent immunosuppression. Dendritic cells (DCs) have an instrumental role in the activation and function of both innate and adaptative immune responses. At least 2 distinct subsets have been characterized in peripheral blood based on phenotypic markers: myeloid DCs (CD11c+), associated with Ag uptake, T cell activation and ability to secrete IL-12, and plasmacytoid DCs, high virus-induced IFN-alpha producing cells. Because of the role of both DC subtypes in antiviral and antitumor induced responses, we hypothesized that DCs could be involved in the onset and evolution of KS., Methods: Thirty-five patients with mediterranean KS assigned to different clinical stages were compared with 51 healthy control subjects. Peripheral blood DCs were quantified and functionally characterised by flow cytometry directly on whole blood samples. The production of the regulatory cytokines, IL-12 and IL-10, was assessed as intracellular accumulation after incubation with or without lipopolysaccharide (LPS)., Results: Myeloid DCs identified as lineage-/HLA-DR+/CD11c+ cells were significantly lower in KS patients than in controls (0.54+/-0.25 vs 0.69 +/-0.26% of the peripheral blood mononuclear cells; p<0.017). Furthermore, CD11c+ DCs were lower in patients with more diffuse disease. Plasmacytoid DCs, identified as lineage-/HLA-DR+/CD123+ cells, were lower in KS patients (0.23+/-0.19 vs 0.36+/-0.17; p<0.001). DCs from KS patients were more mature, as assessed by expression of the maturation marker CD83, and showed an impaired ability to produce IL-12 upon LPS stimulation, as compared with controls., Conclusion: The numerical and functional alterations of peripheral blood DCs observed in KS patients suggest an involvement of these cells in the onset and evolution of the disease.

Background: Paramacular coloboma (plural: colobomata) is a solitary oval football or torpedo-shaped chorioretinal lesion located temporal to the fovea in one or both eyes. Previous case reports have speculated varying etiology, but few have justified its pathognomonic shape and location. We believe it to be congenital in nature and caused by incomplete differentiation of the arcuate bundles along the horizontal raphe in development of the macular architecture. Associated ocular findings may include blepharophimosis, situs inversus, or other anomalous retinal vascular patterns., Case Reports: Three cases of asymptomatic unilateral paramacular colobomata are presented. In each case, a single oval chorioretinal lesion temporal to the macula was found during routine examination. Visual acuity and Humphrey threshold visual field testing were normal with no other associated congenital, systemic, or ocular abnormalities. Because the lesion is nonprogressive, these patients can be followed on an annual basis., Conclusion: Due to their anatomical origin, paramacular colobomata are always located temporal to the macula and have an oval football-shaped appearance. Visual acuity and visual field testing are usually normal, although highly observant patients may be aware of a mild scotoma. Differential diagnosis is important because the clinical appearance can be similar to acquired conditions, most notably age-related macular degeneration and presumed ocular histoplasmosis syndrome.

Three hundred patients with classic Kaposi's sarcoma (CKS) have attended our Department of Dermatology over a period of 20 years. Many of them have been treated by systemic chemotherapy with good responses. Due to the highly variable clinical evolution of the disease, it was, however, often difficult for us to decide whether or not to treat elderly patients. We therefore attempted to establish a new staging system based on objective criteria that more closely follow the clinical variability of CKS and make the therapeutic choices easier. The proposed staging system comprises 4 stages, each further divided according to the speed of disease evolution and presence of complications that can severely impair the quality of life. The application of this staging system to our patients has shown that evolution is prevalently slow in the maculo-nodular and infiltrative stages I and II and faster during the florid and disseminated stages III and IV. Complications are mainly present in the rapidly evolving florid and disseminated stages, with visceral involvement in the more aggressive forms. Based on these findings, we are employing systemic therapy in the florid and disseminated stages and in the infiltrative stage only in case of rapidly evolving or slowly evolving but complicated disease.

Background: Juxtapapillary capillary hemangioblastomas are vascular lesions that occur on the optic nerve head or immediately adjacent to the optic disc. Although juxtapapillary capillary hemangioblastomas may appear as an isolated clinical finding, they are more likely to be a precursor to the diagnosis of von Hippel-Lindau (VHL) disease. When associated with VHL, the ocular complications from hemangioblastoma are generally greater, and subsequently the prognosis is poorer than for isolated entities., Case Report: A 67-year-old white male presented to our clinic complaining of decreased vision in both eyes at distance and near. A dilated fundus examination revealed a swollen left optic nerve. Visual field testing revealed an inferior arcuate defect in the left eye. Laboratory and radiological testing were normal. Fluorescein angiography showed filling during the retinal arterial phase with late diffuse leakage. Based on these results, a diagnosis of juxtapapillary capillary hemangioblastoma was made. This was later confirmed when fundus photographs taken 7 years earlier were obtained, revealing a stable appearance to the nerve., Conclusion: Potential ocular complications of juxtapapillary capillary hemangioblastomas include vision loss secondary to subretinal and intraretinal fluid, as well as epi-retinal membrane formation and, rarely, exudative retinal detachment. Management ranges from observation to surgical intervention, although definitive treatment guidelines have yet to be established. In addition, it is important for the eye care practitioner to be aware of the association with VHL disease, so that patients may be appropriately referred and managed for other possible systemic complications of the disease.

Background: Several drugs are active in aggressive classical Kaposi's sarcoma (CKS); chemotherapeutic agents with fewer side-effects, more rapid response and able to overcome resistance to previous treatment are advisable when treating patients in a second line. Gemcitabine, an analogue of deoxycytidine with cytotoxic activity in the treatment of solid tumours, has been found to have no serious side-effects., Objective: To evaluate the usefulness of treating patients affected by aggressive CKS with gemcytabine., Methods: Twelve patients with a recurrent aggressive form of CKS previously treated with chemotherapy were treated with gemcitabine. The drug was administered intravenously at the dose of 1.2 g/week for 2 weeks, followed by a 1-week interval, until maximal response was reached. Objective responses and toxicity were evaluated according to WHO criteria., Results: Eleven evaluable patients achieved an objective response: CR in 1/11 and PR in 10/11. Toxicity was limited., Conclusion: This study shows the usefulness of treating patients affected with aggressive CKS with gemcitabine, in order to obtain control of the disease and to reduce the related symptoms as well as to overcome a possible resistance to previous treatments., (Copyright 2001 S. Karger AG, Basel.)

Background: Kaposi's sarcoma is a multifocal lympho-angioproliferative disease that appears in elderly subjects of Mediterranean origin (classical form), young Africans and immunodepressed patients (as a result of organ transplantation or AIDS). In 1994, DNA sequences of a new human herpesvirus, called HHV-8, were detected in skin lesions and peripheral blood of patients with AIDS-related Kaposi's sarcoma by confirmational display analysis and polymerase chain reaction., Objective: As HHV-8 in peripheral blood mononuclear cells is detected in about 50% of Mediterranean Kaposi's sarcoma patients and its presence fluctuates in time in the same patient, maybe its detection correlates with the clinical behaviour of the disease., Methods: By using routine and nested polymerase chain reaction we evaluated the presence of HHV-8-specific DNA sequences in the skin lesions, perilesional healthy skin and peripheral blood mononuclear cells of a group of 40 HIV-negative patients with Mediterranean Kaposi's sarcoma., Results: HHV-8 DNA sequences have been found in 40/40 (100%) lesional skin of Mediterranean Kaposi's sarcoma, in 35/40 (85%) perilesional apparently normal skin and in 24/40 (60%) peripheral blood monuclear cell samples. The results of polymerase chain reaction on peripheral blood monuclear cells were positive in 41% of the patients with slowly evolving disease as opposed to 74% of those with rapidly evolving disease, and in 47.6% of the patients with stage I-II disease as opposed to 73.6% of those with stage III-IV., Conclusion: The detection of HHV-8 in peripheral blood monuclear cells seems to correlate with the more aggressive stages and the rapid evolution behaviour of Mediterranean Kaposi's sarcoma., (Copyright 2001 S. Karger AG, Basel)

Background: DNA sequences of human herpesvirus-8 (HHV8) are found in lesions of Kaposi's sarcoma (KS)., Objectives: To verify the hypothesis of the sexual transmission of HHV8 infection., Methods: We used the immunoperoxidase assay to study the prevalence of serum antibodies to HHV8-related antigens in 27 consorts of patients with classical KS, and in a control group of 25 healthy women., Results: Forty-four per cent of the study group were positive, compared with 8% of the controls., Conclusions: The sexual route may be one of the possible ways of transmission of the HHV8 virus.

Hb G-Philadelphia, an alpha-globin allele, is expressed as either 20%, 30%, or 40% of the total hemoglobin. Restriction analyses published thus far have shown that among persons with 30% and 40% hemoglobin (Hb) G the alpha G allele is seen only in a single-locus haplotype. We now report the identification of a second haplotype in which the alpha G allele is found in tandem with an alpha A allele. This haplotype has been found present in DNA from the members of one family in which Hb G is expressed as 20% of the total hemoglobin, determined by both cellulose acetate electrophoresis and high-performance liquid chromatography (HPLC). Synthesis was balanced in all individuals. The identification of a variant alpha-globin allele in two distinct haplotypes presents the possibility of independent mutation. However, an alternative explanation cannot be ruled out; namely, that the original allele may have become distributed among the two haplotypes by unequal crossing-over.

We have investigated differences in C pG methylation between F9 embryonal carcinoma cells in vitro and as tumor cells grown in vivo using Msp I and Hpa II restriction isoschizomers. Southerns were hybridized with two low copy number probes, mouse major beta-globin (f7) and a class I, histocompatibility-2 cDNA clone (pH-2d-4). In each case, the tumor-DNA was hypomethylated while the DNA from F9 cells grown in vitro was moderately methylated. We conclude that growth conditions or cell-cell interactions can greatly affect methylation of C pG sites.