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Photoinduced dermal pigmentation in patients taking tricyclic antidepressants: histology, electron microscopy, and energy dispersive spectroscopy.

Two patients had been taking long-term tricyclic antidepressant therapy. Each developed a blue to slate-gray hyperpigmentation in sun-exposed areas. On histologic examination there were refractile golden brown granules free in the dermis along collagen bundles. Similar pigment was present in macrophages and along the basement membrane zone. The granules stained for melanin, but not for iron, and were bleached by the permanganate method. Electron microscopy showed varying size and shaped electron-dense granules within lysosomes and free in the dermis, which, in unstained sections, showed a less dense peripheral halo. This peripheral halo was also evident on light microscopy. Energy dispersive spectroscopy showed these granules to be rich in copper and sulfur (elements present in tyrosinase and pheomelanin, respectively). We believe that this represents a drug-melanosome complex, which is most likely caused by chronic photoactivation.

Antidepressive Agents, Tricyclic↗

[Amiodarone-induced pigmentation. A histological, ultrastructural study and review of the literature].

Amiodarone is an iodinated cardiac antiarrhythmic drug that causes a slate- gray discoloration of sun-exposed skin. Histopathologically, biopsy specimens of two patients affected by amiodarone pigmentations reveal yellow-brown granules in the reticular dermis, both in the cytoplasm of macrophages and between the collagen bundles. The histochemical stainings of the granules suggest that a lipofuscin pigment rather than melanin is present in the granules. Electron microscopy displays distinctive intracytoplasmic inclusions in many dermal cell types. Six morphologic types can be seen: 1) electron-lucent, membrane bound granules, 2) granules with electron dense nucleus, 3) lamellar "myelin-like" granules, 4) granules with a combination of electron-dense and electron-lucent areas, 5) electron-dense membrane-bound granules, 6) electron-dense no-membrane granules. The different dimensions, structure and shape are related to the structural and aggregational phases of the granules. In particular their pathogenesis may be related to the action of the drug on cell membranes with thesaurismosis, local metabolic damage, accumulation of the drug in the lysosomes and acceleration of the physiological ageing cell process.

Aged↗

Side effects and possible contraindications of amiodarone use.

With the increasing use of amiodarone, several unwanted effects have been recognized. We reviewed 140 patients treated with amiodarone over a 5-year period in an attempt to identify patients at risk, to assess the incidence of these effects and their possible relation to dose, and to determine their outcome. The most common effect was photosensitivity (57% of patients responding to a questionnaire), whereas asymptomatic corneal microdeposits were found in all patients undergoing ophthalmologic examination. In contrast, symptomatic eye changes (colored halos) and slate-gray skin pigmentation were rare. Of the metabolic alterations, the rise in hepatic enzymes correlated with dose and plasma drug and metabolite concentrations (r = 0.59, p less than 0.001; r = 0.62, p less than 0.001, respectively) but was not associated with clinical disease. This relation to dose was not evident in patients developing clinical thyroid abnormalities (two hypothyroidism, two hyperthyroidism), all of whom had normal thyroid function prior to therapy. Four of the five hypothyroid patients were over 70 years of age. No patients developed peripheral neuropathy, but tremor and sleeplessness were common complaints (30% and 28% of patients, respectively) that responded to a decrease in dose. One patient with an abnormal chest x-ray film prior to therapy developed pulmonary fibrosis. We suggest the restricted use of high doses of amiodarone for protracted periods. Patients at particular risk are the older age group (hypothyroidism) and those with abnormal lung function prior to therapy who may be predisposed to pulmonary alveolitis. Most of the observed unwanted effects resolve when amiodarone is decreased in dose or discontinued.

Aged↗

A new UV-sensitive syndrome not belonging to any complementation groups of xeroderma pigmentosum or Cockayne syndrome: siblings showing biochemical characteristics of Cockayne syndrome without typical clinical manifestations.

We report here on two siblings who show no clinical manifestations except for slight cutaneous photosensitivity and cutaneous pigmentation but have biochemical characteristics of Cockayne syndrome (CS). Fibroblasts derived from the patients (Kps2 and Kps3) were 3-4 times more sensitive to UV than normal cells. Although unscheduled DNA synthesis (UDS) in these cells was at a normal level, recovery of RNA synthesis (RRS) after UV irradiation was severely depressed. Microinjection of bacteriophage T4 endonuclease V into the cells corrected RRS after UV irradiation to a level near normal. These results indicate that DNA repair of cyclobutane-type pyrimidine dimers is impaired in the cells and the biochemical characteristics are similar to those of CS cells. However, cell fusion complementation tests with CS group A and B cells resulted in correction of RRS after UV irradiation. Cell fusion with XP group A, B, D, F and G cells also corrected RRS after UV irradiation, and microinjection of cell extracts prepared from Kps3 cells corrected UDS in XP group C and E cells, indicating that the patients do not belong to any complementation group of XP or CS. These results suggest that the patients have a new UV-sensitive syndrome with a biochemical phenotype of CS.

Adolescent↗

Effective stimulation of neutropoiesis with rh G-CSF in dyskeratosis congenita: a case report.

Dyskeratosis congenita (DC) is a rare congenital X-linked disorder. The major clinical manifestations are abnormal skin pigmentation, nail dystrophy, and leukoplakia of mucosal membranes. About 50% of the patients develop bone marrow failure, which is partly responsible for the poor prognosis. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) has been administered to some neutropenic patients with DC, but only a moderate stimulation of neutropoiesis has been observed. We report on a patient with DC treated with recombinant human granulocyte-colony-stimulating factor (rhG-CSF). This treatment resulted in a substantial dose-dependent increase in the neutrophil count.

Adult↗

Carotenemic, skin colour and diabetes mellitus.

Carotenemia with its yellowish-red tint is found in diabetes. The frequency of this phenomenon is unknown and the relationship between skin colour and blood carotenoid level is controversial. Frequently the suspicion of diabetes arising from inspection of the skin colour is in fact confirmed by the usual laboratory tests. We decided to examine skin colour, blood carotenoids, cholesterol and total blood lipid levels in 51 overt diabetics, 42 latent diabetics and 25 healthy subjects as well as 14 patients who had recently suffered an acute myocardial infarction. The healthy subjects showed blood carotenoid levels slightly higher than the patients. As is known, in cases of increased intake of carotenoid-rich fruit and vegetables the yellowish-red skin colour is marked. Diabetic patients however show this phenomenon even though they may not follow such a diet. This finding, although diagnostically useful, does not usually parallel a high carotenoid blood level. From this point of view overt and latent diabetes are similar.

Aged↗

Depigmentation--a rare side effect to intra-articular glucocorticoid treatment.

Intra-articular glucocorticoid injections are often used in patients with rheumatoid arthritis, either as bridging therapy or in periods with increased disease activity. We present a case of local skin depigmentation that occurred at the site of injection in a dark-skinned patient. Depigmentation is a rare complication of such therapy but may have important implications for dark-skinned patients.

Betamethasone↗

Macular coloboma-like lesions and pigment abnormalities as complications of cryotherapy for retinopathy of prematurity in very low birth-weight infants.

PURPOSE: Cryotherapy for retinopathy of prematurity (ROP) is effective in reducing the incidence of blindness in premature infants. However, macular complications associated with successful treatment have not yet been well studied. METHODS: Eighteen very low birth-weight (< 1,251 g) infants (32 eyes) who received cryotherapy for ROP were examined serially for regression of disease and for development of macular abnormalities. Patient characteristics and treatment factors were evaluated to identify risk factors associated with the development of macular abnormalities after successful cryotherapy. RESULTS: Eleven of 32 eyes (34.4%) that had undergone cryotherapy developed significant macular abnormalities, including macular coloboma-like change (six eyes), macular hyperpigmentation (two eyes), irregularly mottled macular hyperpigmentation and hypopigmentation (two eyes), and macular hyperpigmentation and hypopigmentation with subretinal proliferation (one eye). Corrected visual acuity in affected eyes ranged from 0.15 to 0.03 (20/133 to 20/666) compared with 1.0 to 0.2 (20/20 to 20/100) in treated eyes without macular abnormality (P = .0002). No difference in gestational age was noted between infants who did or did not develop macular coloboma-like lesions or pigment abnormalities. Eyes with macular abnormality had more posterior disease (P = .037) and received significantly more cryotherapy than did eyes without macular abnormality (P = .0005). CONCLUSIONS: In very low birth-weight infants receiving cryotherapy for ROP, development of macular coloboma-like lesions and macular pigment abnormalities were related to greater severity of ROP and a greater amount of cryotherapy. Macular abnormalities were associated with markedly worse visual outcomes than were treated eyes without macular abnormality.

Birth Weight↗

Minocycline-induced scleral, dental, and dermal pigmentation.

PURPOSE: To report a case of scleral discoloration secondary to minocycline therapy. METHOD: Case report of a patient referred to a university-based cornea and external disease clinic. RESULTS: The patient had been treated with oral minocycline therapy for adult facial acne for 12 years when she began to develop bilateral blue-gray discoloration of the sclera as well as of the teeth, hard palate, ears, nail beds, and skin. CONCLUSIONS: Chronic systemic minocycline therapy may induce scleral pigmentary changes. The mechanism of discoloration and the long-term natural history upon cessation of minocycline are unclear.

Acne Vulgaris↗

Long-term natural history study of senile retinoschisis with implications for management.

This is a long-term natural history study of 123 consecutive, nonselected patients (218 eyes) with senile retinoschisis examined periodically, while deliberately withholding all forms of treatment, for from 1 to 21 years (average, 9.1 years) so that the natural behavior and prognosis of this disease could be learned and reasonable recommendations for management could be formulated. The quadrant of maximal involvement was the inferior temporal and 74% of the lesions had posterior borders which were postequatorial. Senile retinoschisis was found to be primarily asymptomatic and nonprogressive. Current indications for treatment, treatment modalities, and complication rates published in recent literature are analysed. No case of symptomatic progressive retinal detachment occurred, but there were 14 cases of localized, nonprogressive and asymptomatic "schisis-detachment". Current indications for treatment of senile retinoschisis should be seriously reevaluated and reduced to one primary indication for treatment, namely symptomatic progressive retinal detachment.

Adult↗