Lysosomal, sterol and lipid disorders
Steve Hannigan in Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
Symptoms usually present soon after birth, and include a loss of fat beneath the skin (lipoatrophy), overdeveloped and prominent muscles (muscular hypertrophy), enlargement of the liver (hepatomegaly), and resistance to insulin (both natural and synthetic), which controls blood sugar levels, leading to diabetes mellitus. Other symptoms include darkening and thickening of patches of skin (acanthosis nigricans) and high levels of fats in the blood (hypertriglyceridaemia). There is commonly excessive production of a hormone that causes accelerated growth in height and precocious puberty in childhood, and in adults enlarged hands and feet (acromegaly), prominent ridges above the eyes (supraorbital ridges), enlargement of the upper or lower jaw (prognathism), and enlargement of the genitalia. Other symptoms that may occur in some individuals include excessive production of body hair (hirsutism), a delay in mental development, enlargement of the heart (hypertrophic cardiomyo-pathy), bone cysts, and a prominence of veins (phlebomegaly) in the upper and lower limbs. Acute inlammation of the pancreas (pancreatitis) may also occur.
Oculocutaneous tyrosinemia/tyrosine aminotransferase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The cutaneous lesions are painful keratoses which occur particularly on the peripheral pressure-bearing areas of the palms and soles (Figures 21.5–21.7) [30, 31]. They may occur near the tips of the digits. Subungual lesions may be found. Typical hyperkeratotic lesions are papular, well-demarcated plaques with irregular borders. Diameters up to 2 cm are common, but lesions may be larger and may be hollow or eroded, progressing to crusted, hyperkeratotic areas. They are not pruritic. They are painful and may be associated with hyperhydrosis [32]. They may be heralded by the appearance of blisters. Pain may be so severe that the patient will not walk. Skin lesions may be seen early in life or as late as the second decade [24]. Grayish hyperkeratotic plaques may be seen on the knees, elbows, or ankles. Hyperkeratoses have also been reported on the tongue [33]. Skin biopsy may reveal acanthosis and parakeratosis, as well as hyperkeratosis [30], none of them very specific findings. Electron microscopy may reveal unique thickening of the granular layer and increased tonofibrils and keratohyalin in the palmar and plantar skin along with large numbers of microtubules and unusually tight packing [34]. Crystals of tyrosine were not seen, but they have been seen in the cornea.
Microscopic findings
M. Alan Menter, Caitriona Ryan in Psoriasis, 2017
Guttate disease represents psoriasis at one of its most subtle histopathologic forms and overlaps with that of partially treated disease. Regular acanthosis has not yet developed, such that reliance on other findings is necessary. Dilated, tortuous capillaries are present in edematous dermal papillae and tend to have scattered extravasated erythrocytes and perivascular neutrophils early in the disease (Figure 3.4). Instead of confluent parakeratosis, mounds of parakeratosis are noted (Figure 3.5). Within these mounds are collections of neutrophils, typically “sandwiched” between the layers of parakeratosis. Several findings are distinctly less common in guttate psoriasis when compared with plaque psoriasis: spongiform pustules of Kogoj, dermal edema, and suprapapillary thinning.
Monogenic forms of lipodystrophic syndromes: diagnosis, detection, and practical management considerations from clinical cases
Published in Current Medical Research and Opinion, 2019
Camille Vatier, Marie-Christine Vantyghem, Caroline Storey, Isabelle Jéru, Sophie Christin-Maitre, Bruno Fève, Olivier Lascols, Jacques Beltrand, Jean-Claude Carel, Corinne Vigouroux, Elise Bismuth
Lipodystrophies are rare diseases, and the diagnosis is often overlooked33. LMNA-related lipodystrophy characteristics (e.g. generalized or partial fat atrophy with metabolic changes and insulin resistance) may be due to altered differentiation of adipocytes or changed fat structure34. The principal feature of FPLD2 is loss of fat, commencing at about pubertal age in women, in the buttocks, hips, limbs, and trunk, together with accumulation of fat in the axillae, back, face, labia majora, and visceral region. This distribution of fat, coupled with enhanced and well-defined musculature, means that affected women take on an android appearance. Further, phlebomegaly is often present in the upper and lower limbs, and the hands tend to be broad with small digits. Acanthosis nigricans in the axillae and neck and acrochordons, as signs of insulin resistance, are not infrequent. Women with FPLD2 frequently present with gynecologic disorders such as gestational diabetes, miscarriage, polycystic ovarian syndrome, and stillbirth35. In men, the abovementioned fat-loss changes occur later and are less evident; indeed, men with FPLD2 are typically diagnosed from female kin. Although subcutaneous lipomas are not present in all cases36, their presence should make physicians suspect FPLD2 when a background FPLD phenotype exists. The cardiovascular diversity of FPLD2 is broad and includes early atherosclerotic disease, arrhythmias, hypertrophic cardiomyopathy, and valvulopathies. Atherosclerotic disease and metabolic disturbances are less frequent in men than women with FPLD237.
Chemical peel as an adjuvant treatment in pigmented contact dermatitis: a case series
Published in Journal of Cosmetic and Laser Therapy, 2022
Second patient was 29-year-old female presented with increased facial pigmentation for 20–25 days. There was preceding history of erythema and pruritus following applications of some beauty products. Diffuse hyperpigmentation over forehead, side of the face, chin, and front of the neck sparing the nose and upper lip along with scaling and erythema noted over the lesions (Figure 2a). We kept a diagnosis of pigmented contact dermatitis. Skin biopsy showed mild hyperkeratosis, prominent granular layer, and acanthosis. Dermis shows perivascular and periadenexal moderate lymphohistiocytic infiltrate, few melanophages and pigment incontinence and no basal layer dissolution (Figure 3).
Phenotypic characteristics and risk factors in a multi-ethnic cohort of young adults with type 2 diabetes
Published in Current Medical Research and Opinion, 2019
Nadia Lascar, Quratul-Ain Altaf, Neil T. Raymond, James E. P. Brown, Helen Pattison, Anthony Barnett, Clifford J. Bailey, Srikanth Bellary
Non-alcoholic fatty liver disease (NAFLD) was diagnosed in 11.2% patients, with WE participants showing higher rates of NAFLD compared to SA participants (16.7% vs 7.5%, p = .18). NAFLD was associated with obesity and higher VF; 28.8% of all women were clinically diagnosed with PCOS. PCOS was more common in WE participants and was associated with higher BMI (39.0 ± 11.1 kg/m2 vs 33.0 ± 7.9 kg/m2, p = .030) and VF (12.5 ± 5.6 vs 9.3 ± 4.6, p = .046) compared to those not diagnosed with the disease. Acanthosis nigricans was detected in 12.4% of the cohort and was observed in females only with those of SA ethnicity having greater propensity than WE ethnicity.