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PubMed2003

[Relative contraindication of latanoprost in iris tumors with secondary glaucoma].

INTRODUCTION: Melanocytic iris tumors are often benign and merely require regular follow-up. Evident growth, increasing pigmentation and secondary glaucoma, however, are possible signs of a malignant transformation. PATIENT: We present a 34-year-old male patient showing a localized, mildly prominent hyperpigmentation of the right iris expanding over 2 h. The lesion had been known since childhood and increasing intraocular pressure (IOP) was treated with timolole, dipivefrin and finally with latanoprost. PROGRESSION: The patient was seen for the first time at our hospital 4 years previously, presenting an IOP of 28-30 mmHg of the right eye. The tumor had developed marked heterochromia and a nodular prominent surface, the chamber angle was partly closed and completely hyperpigmented. The ciliary body was not affected by the tumor and standard ultrasound revealed a maximum thickness of 1.2 mm. Over the last 4 years, IOP and heterochromia had increased but without growth of the tumor. An excisional biopsy of the prominent portion was refused by the patient. DISCUSSION: The melanocytic iris tumor described shows malignant characteristics such as progressive heterochromia and secondary glaucoma. However, increasing iris pigmentation can also be caused by topical application of latanoprost. With the evidence of absent tumor growth, there is no reason to suggest malignant degeneration. Generally, in iris naevi or tumors requiring regular follow-up, application of latanoprost should be avoided in order not to conceal the alteration of pigmentation as possible malignant conversion.

Adult↗
PubMed2002

Course and follow-up of solitary Peutz-Jeghers polyps: a case series.

BACKGROUND AND AIMS: Peutz-Jeghers syndrome (PJS) is a rare, autosomal-dominant disease characterized by hamartomatous polyps of the alimentary tract, hyperpigmentation of the skin, and family history of PJS. Rarely, solitary Peutz-Jeghers polyps (PJP) arise in patients without other features of PJS. PATIENTS AND METHODS: We reviewed eight patients since 1979 with solitary PJP, six men and two women. RESULTS: The average age at diagnosis was higher (56+/-13 years) than that of PJS patients in the literature. Polyps were found in the sigmoid colon ( n=4), cecum ( n=1), stomach ( n=1), and duodenum ( n=2). The colonic polyps were diagnosed and removed endoscopically. Indications for colonoscopy included routine screening ( n=4) or rectal bleeding ( n=1). The duodenal and gastric polyps were diagnosed and removed during gastroduodenoscopic examinations, which were performed for nonspecific dyspepsia ( n=2) or gastrointestinal bleeding ( n=1). The median size was 20 mm (range 2 mm-25 mm). Patients were followed for a median of 11.5 years (range 3-22) without another PJP or cancer. Three patients died of causes unrelated to PJP. Five patients are alive and polyp free. CONCLUSION: Solitary PJP do not carry a risk of gastrointestinal cancer and are not an indication for specific high-risk screening.

Adult↗
PubMed1997

["Myxoma syndrome"--a "benign" disease with "malignant" course].

We are reporting on a 36 year-old woman who presented with recurrent cardiac myxomas over a period of nine years. Two of the tumors typically originated in the left atrium and one in the right atrium. Tumor embolization was the presenting symptom twice, leading to reversible cerebral ischemia and minor pulmonary embolism, respectively. The third tumor remained asymptomatic and was detected during routine echocardiographic examination. Based on a positive family history of cardiac tumors, a facially pronounced hyperpigmentation of the skin and the presence of a thyroid adenoma, the diagnosis of a "myxoma syndrome" was established. Patients with "myxoma syndrome" are generally younger than their counterparts with "sporadic myxoma" (mean age at diagnosis 25 vs. 56 years) and have a high frequency of unusual skin freckling (68%). Familial clustering of cardiac myxomas is also frequent (25%). The tumors may be located in any of the cardiac chambers (87% in the atrias, 13% in the ventricles, 50% at multiple sites simultaneously) and have relatively high (18%) 5-year recurrence rate after surgical excision. Since the clinical signs of cardiac tumors are non-specific, diagnosis essentially relies on cardiac imaging by echocardiography, computer tomography, or angiography. The superiority of transesophageal echocardiography is emphasized in this report.

Adult↗
PubMed2002

Pigmentary retinopathy in patients with the MELAS mutation 3243A-->G in mitochondrial DNA.

BACKGROUND: Our objective was to determine the penetrance of retinal pigment epithelium (RPE) abnormalities and other ophthalmologic manifestations in patients with the 3243A-->G mutation in mitochondrial DNA. METHODS: Adult members in two generations were examined from a population-based cohort of 13 pedigrees with 3243A-->G. Twenty-six patients underwent a thorough ophthalmological examination. A chart review was carried out on an additional 44 patients. RESULTS: Paramacular RPE atrophy and areas of hyperpigmentation were found in 10 patients (38%; 95% confidence interval 20-59%). Electroretinography was normal in only one of the eight patients tested, whereas dark adaptation was abnormal in two. RPE abnormalities were associated with more severe clinical phenotypes and higher degrees of 3243A-->G mutation heteroplasmy in muscle. Ten patients had diabetes mellitus, nine of whom had also RPE abnormalities. This finding, however, reflected the severity of the phenotype, and diabetic retinopathy was confidently diagnosed in only two patients. External ophthalmoplegia was detected in occasional patients. CONCLUSION: RPE abnormalities were found in this population-based cohort at a frequency that was lower than that reported earlier. RPE abnormalities were associated with more severe phenotypes, suggesting that they are expressed in patients with syndromic features. RPE abnormalities and diabetes mellitus co-occurred frequently, but diabetic retinopathy was not common.

Adult↗
PubMed2002

Inter- and intra-observer variability in grading lesions of age-related maculopathy and macular degeneration.

PURPOSE: To introduce a revised version of the grading system established by the International ARM Epidemiological Study Group for identifying and quantifying abnormalities of age-related maculopathy (ARM) and age-related degeneration (AMD) and to investigate its reliability, specifically the inter- and intra-observer variability. METHODS: Fifty eyes of 25 patients with ARM or AMD in at least one eye were randomly selected from a large ongoing collection of clinical data and DNA in a tertiary referral UK population. Stereoscopic color fundus photographs were taken with a 30 degrees fundus camera and were centered on the macula. Presence and severity of fundus abnormalities in ARM and AMD were graded using a grid to define macular subfields and standard circles to define the size of lesions. Inter-observer variability was assessed by having three retinal specialists evaluate the color slides and intra-observer variability by re-grading the same set. RESULTS: The inter-observer agreement for all subfields was fair to substantial for small hard drusen (70-89%; kappa=0.26-0.63) and intermediate soft drusen (76-94%; kappa=0.27-0.69). Agreement ranged between 87% and 100%, between 50% and 92%, and between 78% and 100% for larger drusen, the presence of hyperpigmentation, and the presence of hypopigmentation, respectively. Agreement was moderate to almost perfect for the presence of geographic atrophy (88-98%; kappa=0.60-0.95) and substantial to almost perfect for the presence of choroidal neovascularization (84-100%; kappa=0.62-1.00). The intra-observer variability for the grading of drusen characteristics and pigmentary changes was similar in magnitude, but slightly greater for features of advanced AMD. CONCLUSION: Reproducibility was achieved using a revised version of the grading system established by the International ARM Epidemiological Study Group. This grading system may therefore be used for phenotyping of ARM and AMD.

Diagnostic Techniques, Ophthalmological↗
PubMed2007

Indocyanine green angiographic findings of Dalen-Fuchs nodules in Vogt-Koyanagi-Harada disease.

PURPOSE: The purpose of this study was to analyze indocyanine green (ICG) angiographic findings of Dalen-Fuchs nodules in Vogt-Koyanagi-Harada (VKH) disease. METHODS: ICG angiograms of 15 patients (30 eyes) with Dalen-Fuchs nodules in VKH disease of between 2 months and 5 years after the initial diagnosis were retrospectively studied. Findings of ICG angiography were compared with features of fundus fluorescein angiography (FFA). RESULTS: Dalen-Fuchs nodules were easily found in the inferior (30 eyes, 100%) and temporal periphery (22 eyes, 73%) and showed two kinds of fluorescence in ICG angiography. In ten patients (20 eyes), the nodules showed small round hypofluorescent dark dots in the whole process of angiography, and the dark dots were larger in size than the nodules in FFA. Disease course in these patients was relatively long-between 1 year and 5 years. On clinical examination, the nodules were atrophic, and hyperpigmentation was found around them. In another five patients (ten eyes), parts of the nodules showed small hyperfluorescent dots in the early phase, but they were faint in the intermediate phase and became large, hypofluorescent dark dots in the late phase. Disease course in these patients was between 2 and 8 months. The nodules were bright yellow, fresh, and much larger than those in the first kind of ICG fluorescence. CONCLUSIONS: Dalen-Fuchs nodules in VKH are mostly present in the inferior and temporal periphery. The two kinds of fluorescence of Dalen-Fuchs in ICG angiography may reflect obliteration of choriocapillaris under the nodules and different quantities of lipofuscin in the nodules at different time points of the disease.

Adult↗
PubMed1999

Variability of RPE reaction in two cases after selective RPE laser effects in prophylactic treatment of drusen.

BACKGROUND: The value of prophylactic photocoagulation of soft drusen is unclear. Photocoagulation is usually performed by a continuous wave laser. METHODS: We report the cases of two patients with age-related macular degeneration with soft drusen who were treated by selective retinal pigment epithelium (RPE) photocoagulation of a pulsed Nd:YLF (527 nm) laser. Laser parameters were: wavelength 527 nm, number of pulses in a train 500, pulse duration 1.7 microseconds, energy per pulse 70 microJ, spot size 160 microns, repetition rate 500 Hz. RESULTS: Dosimetry performed individually showed that in both patients laser photocoagulation was performed at the threshold of RPE disruption. None of the laser effects was visible during photocoagulation. They were detectable only by fluorescein angiography. Despite identical photocoagulation parameters the RPE reaction was completely different. In the first patient RPE hyperpigmentation was notable at most photocoagulation sites and the drusen had disappeared after 6 months. In the second patient the laser effects were not visible after 6 months by biomicroscopy and the drusen stayed unchanged. CONCLUSION: These findings could reflect different repair mechanisms of the RPE after alteration and could represent a sign of a different viable stage in the life of RPE cells. Close attention should be paid to this phenomenon in the various drusen studies currently under way.

Fluorescein Angiography↗
PubMed1999

Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas.

PURPOSE: To assess the effects of intravitreal injection of recombinant tissue plasminogen activator (rTPA) and gas on submacular hemorrhage in age-related macular degeneration (ARMD). METHODS: Eleven consecutive patients (11 eyes) with subretinal hemorrhage due to ARMD involving the fovea with elevation of the neurosensory retina were included in this study. Subretinal hemorrhage occured 12 h to 14 days before onset of therapy. Injection of rTPA through the pars plana in a dose of 50 or 100 microg was performed. Gas instillation (0.2-0.4 ml) followed rTPA injection, either immediately after injection (7 patients) or during the following day (4 patients). RESULTS: After intravitreal injection of rTPA, subretinal clots were totally or partially liquefied when treatment started up to 3 days after onset of bleeding. In all patients treated with 100 microg rTPA a large exudative retinal detachment of the inferior retina resulted, which reabsorbed spontaneously within 2 weeks. After reattachment of the exudative retinal detachment hyperpigmentation of the retinal pigment epithelium was noted. Temporary opacification of the vitreous was observed between the 2nd and 7th postoperative day in 5 eyes (45.5%). Postoperative visual acuity increased in 5 patients (45.5%). CONCLUSION: Intravitreal application of rTPA followed by gas injection is a sufficient and convenient technique for effective removal of freshly formed submacular hemorrhage. Removal is mediated through combined enzymatic (rTPA) and mechanical (gas) effects. This technique offers a quick recovery of vision in eyes with less severe ARMD.

Acute Disease↗
PubMed2007

Hepatocellular carcinoma arising from ectopic liver tissue in the pancreas.

Liver tissue ectopia is a well-documented phenomenon. Rarely, hepatocellular carcinoma arises from the ectopic liver tissue. In this paper, we report a case of a primary, well-differentiated hepatocellular carcinoma arising from ectopic liver tissue in the pancreas. The patient is a 58-year-old Hispanic man with no history of underlying liver diseases or chronic pancreatic diseases. Patient presented with a several days history of abdominal pain with radiation to his right upper quadrant. Imaging study revealed a 3.7 x 3.3-cm mass in the distal pancreas. No other lesions were identified. Preoperative fine needle aspiration revealed blood and atypical hepatocytes. The patient underwent distal pancreatectomy and splenectomy for suspected neuroendocrine tumor. Gross examination revealed a well-circumscribed 3.3-cm, beige-tan, pseudolobulated tumor with focal areas of hyperpigmentation. A microscopic examination revealed hepatoid cells arranged in a trabecular pattern with focal bile pigment. Immunohistochemistry study showed that the tumor cells were reactive with hepatocyte antigen (Hep par 1), alpha-1 antitrypsin, but negative for synaptophysin and chromogranin. Immunostain for polyclonal carcinoembryonic antigen showed a typical bile canalicular pattern. These results support that this tumor in the pancreas is hepatocellular carcinoma, most likely arising from ectopic liver tissue within the pancreas.

Carcinoma, Hepatocellular↗
PubMed2003

A novel dysmorphic syndrome with open calvarial sutures and sutural cataracts maps to chromosome 14q13-q21.

We describe a new dysmorphic syndrome in an inbred Saudi Arabian family with 21 members. Five males and one female have similar craniofacial features including wide open calvarial sutures with large and late-closing anterior fontanels, frontal bossing, hyperpigmentation with capillary hemangioma of the forehead, significant hypertelorism, and a broad and prominent nose. In addition, these individuals have Y-shaped sutural cataracts diagnosed by 1-2 years of age. No chromosomal or biochemical abnormalities were identified. A genome-wide scan was performed, and two-point LOD score analysis, assuming autosomal recessive inheritance, detected linkage to chromosome 14q13-q21. The highest LOD scores were obtained for marker GATA136A04 (LOD=4.58 at theta=0.00) and for the adjacent telomeric marker D14S1048 (LOD=4.32 at theta=0.00). Multipoint linkage analysis resulted in a maximum LOD score of 5.44 between markers D14S1048 and GATA136A04. Model independent analysis by SIBPAL confirmed linkage to the same chromosomal region. Haplotype analysis indicated that all affected individuals were homozygous for the interval on chromosome 14q13-q21 with two recombinants for D14S1014 (centromeric) and one recombinant for D14S301 (telomeric). These recombinations limit the disease locus to a region of approximately 7.26 Mb. Candidate genes localized to this region were identified, and analysis of PAX9 did not identify mutations in these patients. The unique clinical phenotype and the mapping data suggest that this family represents a novel autosomal recessive syndrome.

Abnormalities, Multiple↗
PubMed2003

Cronkhite-Canada syndrome with colon cancer, portal thrombosis, high titer of antinuclear antibodies, and membranous glomerulonephritis.

A 64-year-old man, who came to us with diarrhea, presented with ectodermal changes such as hyperpigmentation, alopecia, and onychatrophy, and was affected by polyposis in the colorectum and stomach. The polyps were histologically consistent with those in Cronkhite-Canada syndrome (CCS). Interestingly, the patient also had colon cancer, as well as portal thrombosis and a high concentration of antinuclear antibody. Treatment with prednisolone ameliorated the symptoms and the gastrointestinal polyposis, while the cancer was successfully treated with a hemicolectomy. Six months after the surgery, the patient developed nephropathy, with nephrotic-range proteinuria, without recurrence of the cancer. The biopsied renal specimen showed membranous glomerulonephritis. This is a rare case of CCS associated with various complications such as colon cancer, portal vein thrombosis, a high titer of antinuclear antibodies, and membranous glomerulonephritis. Although the pathogenesis of CCS is essentially unknown, these complications might have been indicative of an underlying immunological abnormality.

Antibodies, Antinuclear↗
PubMed2000

Recent progress in the genetics of incontinentia pigmenti (Bloch-Sulzberger syndrome).

Incontinentia pigmenti (IP) is a rare disorder which affects organs and tissues of ectodermal and mesodermal origin. It is characterized by swirled patterns of hyperpigmentation. In some cases, the condition is also associated with malformations of the teeth, nails, skeleton, hair, eyes, and the central nervous system. The disorder is inherited as an X-linked dominant trait and mostly affects females. However, there have been several cases of IP in males that survived to birth. While IP in females could be caused by a skewed pattern of X-inactivation, three mechanisms: namely, the half-chromatid hypothesis, unstable premutation, and a higher rate of de-novo germline mutations, have been proposed to explain the survival of affected male patients. Cytogenetic studies in several sporadic cases with signs similar to IP exhibited an X/autosomal translocation involving a breakpoint at Xp11, suggesting a gene locus on Xp11 (IP1). Linkage analysis of familial IP, on the other hand, has identified a second locus, in the Xq28 region (IP2). Molecular genetic analysis of two candidate genes located at Xp11 and Xq28, as well as the human homologue of the murine Str gene, failed to reveal any disease-causing mutations. Although heterozygous female mice deficient for the IKKgamma/NEMO gene exhibited dermatopathy similar to that in human IP, studies of the gene in human IP have not yet been available. In an effort to isolate the genes causing IP, cosmid clones containing the translocation breakpoint located at Xp11 and the transcriptional map of the Xq28 region were constructed. These maps could be invaluable tools in the identification of genes in the near future.

Animals↗
PubMed2002

Ochronosis: a case of severe ochronotic arthropathy.

Ochronosis involves primarily the large cartilaginous joint surfaces, ribs, intervertebral discs, ear cartilage etc. We report on a 53-year-old woman with typical alkaptonuric ochronosis with dark urine, blue-black pigmentation of the auriculae and hands, focal brown hyperpigmentation of the sclera, spondylarthropathy and severe shoulder joint involvement.

Alkaptonuria↗
PubMed2004

Treatment of superficial cutaneous vascular lesions: experience with the KTP 532 nm laser.

Whilst most facial telangiectasias respond well to short-pulse-duration pulsed dye laser therapy, studies have shown that for the treatment of larger vessels these short-duration pulses are sub-optimal. Long-pulse frequency-doubled neodymium:YAG lasers have been introduced with pulse durations ranging from 1-50 ms and treatment beam diameters of up to 4 mm. We report the results of KTP/532 nm laser treatment for superficial vascular skin lesions. The aim was to determine the efficacy of the KTP/532 nm laser in the treatment of superficial cutaneous vascular lesions at a regional dermatology centre in a 2 year retrospective analysis. Patients were referred from general dermatology clinics to a purpose-built laser facility. A test dose was performed at the initial consultation and thereafter patients were reviewed and treated at 6 week intervals. Outcome was graded into five classifications by the patient and operator independently based on photographic records: clear, marked improvement, partial response, poor response, and no change or worsening. Over the 2 year period, 204 patients with 246 diagnoses were treated [156 female; median age 41 (range 1-74) years; Fitzpatrick skin types I-III]. Equal numbers of spider angioma (102) and facial telangiectasia (102) were treated. Of those patients who completed treatment and follow up, 57/58 (98%) of spider angiomas and 44/49 (90%) of facial telangiectasia markedly improved or cleared. Satisfactory treatment outcomes, with one clearance and two partial responses, occurred in three of five patients with port-wine stain. Few patients experienced adverse effects: two declined further treatment due to pain, and a small area of minimal superficial scarring developed in one case. Two patients developed mild persistent post-inflammatory hyperpigmentation, and one subject experienced an episode of acute facial erythema, swelling and blistering after one treatment. The KTP/532 nm frequency-doubled neodymium:YAG laser is a safe and effective treatment for common superficial cutaneous vascular lesions in patients with Fitzpatrick skin types I-III.

Adolescent↗
PubMed2007

Treatment of 153 Japanese patients with Q-switched alexandrite laser.

We have recently used Q-switched alexandrite laser for the treatment of various kinds of pigmented skin lesions. We retrospectively compared therapeutic outcomes of 153 Japanese patients who consulted our department. This approach was not very efficient for nevus spilus/café-au-lait spots, which seemed laser-resistant, especially when the pigmentation had appeared after 1 year of age, was treated after 5 years of age, was located on the face, was oval with a smooth border, and the patient was male. This approach was equally effective for senile lentigo, nevus of Ota, and Mongolian spots, but less effective for acquired bilateral nevus of Ota-like macules. Some patients with sacral Mongolian spots or those with light-colored, senile lentigo developed severe post-inflammatory hyperpigmentation after treatment. As a whole, good therapeutic outcome was achieved after multiple treatment sessions. However, the use of other lasers or other treatment modalities should be considered to treat nevus spilus/café-au-lait spots.

Beryllium↗
PubMed2003

Basaloid follicular hamartoma with trichoblastomatous proliferations.

BACKGROUND: Basaloid follicular hamartomas (BFH) are rare, benign, adnexal lesions with diverse clinical presentations. Previous studies documented BFHs with fibroepithelioma of Pinkus-like proliferations, or proliferations that resemble trichoepitheliomas. OBJECTIVE: We report on a patient with linear, unilateral BFH and extensive trichoblastomatous proliferations involving the right arm, torso, and leg. An 18-year-old female presented with multiple, hyperkeratotic, linear nodules and plaques limited to her right side from the shoulder to the leg. The lesions had existed since birth and gradually increased over time. RESULTS: The lesions contained hyperpigmented, exophytic nodules with acanthosis, pseudoepitheliomatous hyperplasia, focally associated with hyperkeratosis, and squamous eddies. Some areas contained trichoepithelioma-like proliferations, or large nodules of basaloid cells with numerous cystic spaces, marked hyperpigmentation, and melanophages. The diagnosis was linear, unilateral BFH with an unusual trichoblastomatous component. CONCLUSION: While trichoblastomatous proliferations could occur in a BFH, to our knowledge this finding has not been reported.

Adolescent↗
PubMed2007

Progressive retinal dystrophy in two sisters with glutathione synthetase (GS) deficiency.

We report the ophthalmological findings of two sisters with severe glutathione synthetase deficiency, an autosomal recessive inborn error of metabolism resulting in very low intracellular levels of the free-radical scavenger glutathione. The patients were investigated because of declining visual acuity. The most prominent finding was progressive retinal dystrophy with hyperpigmentations and maculopathy. Generally disturbed functioning of both the outer and inner layers of the retina resulted in attenuated or nearly abolished electroretinograms. These findings agree with a rod/cone type of retinal dystrophy, and we suggest that this is due to glutathione deficiency. Treatment with antioxidants such as vitamins E and C seems to prevent the progression of CNS damage. We speculate that it might also prevent retinal dystrophy in patients with glutathione synthetase deficiency. We suggest that patients with retinal dystrophy and additional neurological signs should be investigated for a defect in glutathione metabolism. Also, we recommend that patients with low levels of glutathione should be examined for retinal dystrophy. Our results suggest that a decreased capacity for scavenging reactive oxygen species and/or increased oxidative stress may cause retinal dystrophy. If this is the case, the redox state in the retina should be a potentially useful therapeutic target to prevent reduced visual function and blindness.

Antioxidants↗
PubMed2006

Clinical and biochemical stabilization of Nelson's syndrome with long-term low-dose cabergoline treatment.

We report the results of long-term (6-year) treatment of Nelson's syndrome with the long-acting dopamine agonist, cabergoline, in a 55-year-old woman. The disease presented 26 years after bilateral adrenalectomy and radiation treatment for Cushing's disease, followed by glucocorticoid and mineralocorticoid replacement therapy. Signs of Nelson's syndrome included skin and mucosal hyperpigmentation accompanied by elevated plasma levels of adrenocorticotropic hormone (ACTH) (984 pmol/l; normal, 2.0-11.5 pmol/l). Magnetic resonance imaging of the pituitary demonstrated sellar enlargement with a 15 mm macroadenoma. The patient was initially treated with bromocriptine (10 mg/d) which had no effect on either ACTH level or tumor mass. Because of visual loss, transsphenoidal surgery was performed, with partial excision of the adenoma and chiasmal decompression, followed by radiosurgery. However, ACTH levels improved only temporarily, and then increased to previous levels. Therefore, cabergoline treatment (1.5 mg/week) was initiated. ACTH levels decreased dramatically from 1050 to 132 pmol/l, accompanied by clinical improvement. Repeated imaging studies demonstrated a stable residual pituitary tumor. This case demonstrates that long-term cabergoline treatment may be efficient in patients with Nelson's syndrome.

Cabergoline↗