Progressive Hyperpigmentation Research Articles

A novel KITLG mutation causes familial progressive hyperpigmentation and hypopigmentation with multiple café-au-lait macules

A novel <i>KITLG</i> mutation causes familial progressive hyperpigmentation and hypopigmentation with multiple café-au-lait macules

Progressive Hyperpigmentation on the Face in a Skin of Color Woman: Challenge.

Progressive Hyperpigmentation on the Face in a Skin of Color Woman: Challenge.

Progressive Hyperpigmentation on the Face in a Skin of Color Woman: Answer.

Progressive Hyperpigmentation on the Face in a Skin of Color Woman: Answer.

Carbon Baby Syndrome: A Case Report with Review of Literature

Abstract Carbon baby syndrome also known as universal acquired melanosis is one of the rare causes of diffuse and progressive hyperpigmentation of the skin. A case of a 9-year-old Nepali child was reported in whom darkening of the skin began at the age of 5 months. At presentation, generalized hyperpigmentation was observed with characteristic sparing of pressure areas over the palms and soles. The diagnosis was established by histopathological evidence of epidermal and dermal melanization after the exclusion of all cutaneous and systemic causes for such hyperpigmentation. This case is reported for its rarity and unusual clinicohistopathological features.

FRI195 Tuberculosis and Adrenal Glands: The Great Forgotten

Abstract Disclosure: I. Vina: None. R. Sánchez: None. I.C. Fernández: None. C. Vázquez: None. Background: Tuberculous adrenalitis is an extremely rare cause of Addison disease in developed countries. Since more than 80% of the primary adrenal insufficiency cases in the developed world are caused by autoimmune disease, tuberculous adrenalitis often go unnoticed. The aim of this case report is to remember that, even if it is not frequent, TB cannot be overlooked as a cause of longstanding primary adrenal insufficiency, even without evidence of pulmonary or extra glandular TB disease. Herein, we reported a case of bilateral tuberculous adrenalitis, wherein the patient initially presented with gastrointestinal symptoms, hyperpigmentation, bilateral adrenal masses, and no evidence of extra-adrenal tuberculosis. Case report: A 57-year-old woman from Madrid with no medical relevant history, was admitted to our hospital with 4 months of evolution of asthenia, weight loss (-8kg) and nausea that in recent days has been accompanied by fever and anorexia. He also refers progressive hyperpigmentation for the past 3 years. Denies recent travel abroad. On physical examination hypotension (80/53 mmHg) and generalized hyperpigmentation predominantly in the oral mucosa stand out. Blood test: Glu: 41 mg/dL, Na+: 122 mmol/L, K+: 4.8 mmol/L, ACTH: 922 pg/mL, Cortisol: 4.63 ug/dL, Anti-Hydroxylase Ab and Anti-Adrenal glands Ab: negative A computed tomography scan of the abdomen with intravenous contrast revealed bilaterally enlarged adrenal glands with small bilateral calcifications (12-18mm). TB QuantiFERON test: positive. She was initially treated with saline serum and intravenous hydrocortisone causing her symptoms to improve significantly in a few days and was subsequently discharged on hydrocortisone and fludrocortisone and proper treatment for TB Adrenalitis and follow-up in outpatient clinics. Conclusions: Although not frequent, infectious causes should always be kept in mind, such as the etiology of adrenal insufficiency in a patient with long-term compatible symptoms, even though it is a developed country, given world globalization, which makes infectious diseases highly transmissible between countries and continents. Presentation: Friday, June 16, 2023

A novel p.Leu197Pro homozygous variant in HSD3B2 as a cause of 46,XY DSD with hyperpigmentation in an infant

We report a novel missense variant of the HSD3B2 gene in a 46,XY child born to third degree consanguineous parents presenting with undervirilization and progressive hyperpigmentation. The steroid profile showed elevated concentrations of 17-hydroxyprogesterone, but normal androstenedione and testosterone. The adrenocorticotropic hormone was elevated. The direct DNA sequencing of the child revealed a new homozygous missense variant in the HSD3B2 gene, resulting in the amino acid substitution of proline for leucine at codon 197. We have described a hitherto novel HSD3B2 gene variant in an undervirilized male infant causing 3β-hydroxysteroid dehydrogenase 2 deficiency.

Clinical phenotype and genetic analysis of a Chinese pedigree affected with familial progressive hyperpigmentation and hypopigmentation

To explore the clinical phenotype and genetic basis for a Chinese pedigree affected with familial progressive hyperpigmentation and hypopigmentation (FPHH). Clinical data and family history for a child with FPHH were collected. Peripheral blood samples were collected from the child, his parents and two sisters. Following the extraction of DNA, high-throughput sequencing was carried out to screen for genetic variant associated with the disease. Candidate variant was verified by Sanger sequencing of his family members. The main clinical features of the proband have included progressive hyperpigmentation and hypopigmentation. High-throughput sequencing revealed that he has harbored a heterozygous c.105T>A (p.Asn35Lys) variant of the KITLG gene, which was unreported previously. Sanger sequencing confirmed that the variant has co-segregated with the disease phenotype in his pedigree. For infants with progressive skin pigmentation and hypopigmentation spots, FPHH should be suspected. The heterozygous c.105T>A (p.Asn35Lys) variant of the KITLG gene probably underlay the FPHH in this pedigree.

Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss.

BackgroundPathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non‐syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper‐ and hypopigmentation, all of which are inherited in an autosomal dominant manner.ObjectivesTo describe the genotypic and clinical spectrum of biallelic KITLG‐variants.MethodsWe used a genotype‐first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports.ResultsWe describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a ‘sock‐and‐glove‐like’, symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss‐of‐function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory‐pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism.ConclusionsWe provide consolidating evidence that biallelic KITLG variants cause a distinct auditory‐pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT‐related piebaldism.

Progressive hyperpigmentation over hands and feet in a young male.

Progressive hyperpigmentation over hands and feet in a young male.

Progressive Axillary Hyperpigmentation.

Progressive Axillary Hyperpigmentation.

Variations in the Initial Presentation of a Rare Congenital Adrenal Hyperplasia: Steroidogenic Acute Regulatory Deficiency

Background: Steroidogenic Acute Regulatory (StAR) deficiency is a rare form of congenital adrenal hyperplasia characterized by dysregulated cholesterol transport mediated by StAR enzyme across mitochondrial membranes. Adrenal dysfunction is due to the two-hit hypothesis: 1) defective StAR protein and 2) cholesterol accumulation in the adrenals and gonads. With variable cellular damage, adrenal crisis can occur early or late. Clinical cases: We present two cases of StAR deficiency with contrasting presentations. Case 1: A 9-day old ex full term female from a nonconsanguineous union presented to a rural hospital with hypothermia, lethargy, and poor feeding. She had hypoglycemia 41 mg/dL (60–105), hyponatremia 120 mEq/L (135–145), hyperkalemia 7.7 mEq/L (3.5–5.5) and cortisol < 0.4 ug/dL (4.5–23). Baby was started on hydrocortisone (HCT) 100 mg/m2 and one-time fludrocortisone (FCT). She decompensated requiring chest compressions, intubation and pressors. She was transferred to our institution. Newborn screen was normal; she had typical female external genitalia. US demonstrated a uterus; ovaries and adrenals were not identified. Upon extubation and clinical improvement, her HCT was weaned to physiologic doses. She became hyponatremic requiring FCT and salt supplements. Post-HCT wean, ACTH level was 304 pg/mL (7–63) with aldosterone < 4.0 ng/dL (6.5–86). Karyotype was 46,XX. Genetic analysis revealed a novel heterozygous likely pathogenic variant in the STAR gene, (STAR c.65-12_68del variant) without defect in the other STAR gene. Case 2: A 9-month-old ex full-term female of Iraqi descent from a nonconsanguineous union presented with fatigue, poor oral intake and weight loss from 50%-ile to 3%-ile. She had hyponatremia 122 mEq/L, hyperkalemia 8.0 mEq/L, but was normoglycemic. She was normotensive; EKG was normal. Parents noted progressive hyperpigmentation including her gums, palmar and plantar creases. She had typical external female genitalia with a hypoplastic clitoris (2 mm x 2 mm). ACTH stimulation test showed low cortisol (0.5 ug/dL) at 60 minutes. She was treated with HCT 100 mg/m2 for 5 days, then tapered to maintenance dosing, with FCT and salt supplements. Her ACTH level returned > 5000 pg/ml. Aldosterone, 17-OH-Progesterone, 17-OH-Pregnenolone, 11-Deoxycortisol and androstenedione were undetectable. Pelvic US did not identify uterus or ovaries. Pelvic MRI identified bilateral inguinal testes with enlarged adrenal glands. Karyotype was 46, XY. We suspected StAR deficiency with sex-reversal. Genetic analysis revealed a known homozygous mutation in STAR (c.545G>A). Conclusion: StAR deficiency is clinically indistinguishable from P450scc deficiency and genetic testing is needed. Both entities can present with early or delayed adrenal crisis. While classic for StAR deficiency, adrenal enlargement is inconsistent. Karyotype is vital to identify sex reversal.

Addisonian pigmentation of tubercular etiology-A case report

Addisonian pigmentation is defined as hyperpigmentation of both exposed and unexposed parts of the body and it typically occurs in primary adrenal insufficiency. We hereby report a case of a 15 year old boy who presented with progressive hyperpigmentation of the face, trunk, chest, abdomen and extremities which was more accentuated over the sun exposed areas. He also had` pigmentation of nails, oral and genital mucosa, palms and soles with accentuation over palmar creases. Routine blood investigations were found to be normal. His serum electrolytes showed hyponatremia and hyperkalemia with evidence of hypocortisolemia and` increased serum ACTH. Chest x-ray was suggestive of pulmonary tuberculosis, sputum AFB was positive and Mantoux reaction was strongly positive. CT scan showed bilateral adrenal calcification. All these investigations confirmed primary adrenal insufficiency due to tuberculosis and ATT was initiated along with steroid replacement therapy. Keywords: Addisonian pigmentation, ACTH, hyperpigmentation.

Why is My Skin Turning Black? A Rare Side Effect of Capecitabine

Introduction: Capecitabine is an oral chemotherapy frequently used in the treatment of metastatic breast and colorectal cancers. Drug-induced cutaneous hyperpigmentation is a rare adverse effect of capecitabine, which is almost exclusively reported with development of hand-foot syndrome (HFS). Here, we report a case of capecitabine-induced hyperpigmentation affecting the hands, feet, face, and tongue in the complete absence of HFS.Case report: An 82-year old man presented with progressive hyperpigmentation of his hands, feet, face, and tongue shortly after initiating capecitabine for treatment of colon adenocarcinoma. There was no associated erythema, edema, blistering, desquamation, tingling, or tenderness. After completion of capecitabine therapy, he endorsed 95% resolution of all hyperpigmentation.Discussion: Previous reports of capecitabine-induced hyperpigmentation have argued that it may be a sign of impending toxicity and should be a part of the HFS grading scale. Others argue that the two are separate entities, yet the mechanism is still unknown. This case supports that capecitabine can cause hyperpigmentation independent of HFS, and thus, should be evaluated as a separate entity of HFS if other symptoms are lacking.

Adult onset progressive cribriform and zosteriform hyperpigmentation: a rare presentation

Adult onset progressive cribriform and zosteriform hyperpigmentation: a rare presentation

SUN-604 Dermatomiositis in a Patient with Papillary Thyroid Cancer: Simple Association or Paraneoplastic Syndrome?

The presentation of Dermatomyositis as a paraneoplastic syndrome is known. It is associated with malignancy of lung, pancreas, ovary, gastrointestinal and lymphoma not hodking. In thyroid neoplasias, the evidence is almost nil, with 8 cases published to date. Remission of Dermatomyositis does not always occur after thyroidectomy.A 24-year-old woman with hypothyroidism in treatment. In 6 months progressive hyperpigmentation is added in front, malar, nasogeniana, axillary, lumbar and popliteal region; asthenia and proximal muscle weakness that intensifies until hospitalization. On examination: 3N goiter, right thyroid nodule palpable, TSH: 4.9, T4L: 1.1, total CPK: 6579, LDH: 2791, popliteal and lumbosacral hyperpigmentation biopsy: Acanthosis Nigricans. Electromyography: Inflammatory Myopathy, Muscle Biopsy: Dermatomyositis. ANA: speckled pattern 1: 320, other exams: normal. With these findings and fulfilling the criteria of Bohan and Peter is diagnosed Dermatomyositis. We proceed to the search for hidden neoplasms discarding those commonly associated. Thyroid ultrasound: hypoechoic image in left lobe, vascularized, ill-defined edges of 11x10 mm. BAAF: Bethesda VI. Thyroglobulin: 6.84 ng / m, Anti-thyroglobulin: 67.68 IU / mL. Total thyroidectomy was performed with group VI dissection. AP: Classic type Papillary Carcinoma pT3N1a. Dermatomyositis was managed with pulses of methylprednisolone leaving the hospital with oral corticotherapy, there was moderate improvement in muscle weakness, with persistence of hyperpigmentation.Although there is controversy between the association of these two entities, we consider it important to include thyroid cancer in the search for hidden neoplasms. The corresponding permission was requested to the patient to use his information for academic purposes.

Photosensitivity and hyperpigmentation secondary to amiodarone: single case report

We report and emblematic case of a 65years-old male patient with cutaneous photosensitivity and progressive hyperpigmentation of photo exposed skin after continuous use of amiodarone to treat an atrial fibrillation developed along with chronic obstructive pulmonary disease. Relevant literature was consulted and is discussed together with the findings of the case.

Familial Glucocorticoid Deficiency Presenting as Progressive Hyperpigmentation

Familial Glucocorticoid Deficiency Presenting as Progressive Hyperpigmentation

Dermosccopic features of progressive cribriform and zosteriform hyperpigmentation

Dermosccopic features of progressive cribriform and zosteriform hyperpigmentation

Familial Glucocorticoid Deficiency Presenting as Progressive Hyperpigmentation: A Case Report

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease caused by resistant of ACTH receptor at adrenal cortex leading to (usually) isolated glucocorticoid deficiency with normal mineralocorticoid secrete. Patients with FGD usually presented in neonatal–childhood period with signs/symptoms of glucocorticoid deficiency such as hypoglycemia, hyperpigmentation, Failure to thrive, shock and death if treatment was delayed. Labs usually revealed high ACTH, low cortisol but normal 17 OHP, electrolyte, androgen. Here we describe a 3-yearsold Saudi girl, with history of progressive hyperpigmentation for first year of life, but no history of hypoglycaemia or neonatal jaundice, no history of a lacrimation or dysphagia and positive similar family history. She had generalized Hyperpigmentation with normal female genitalia. Her cortisol was low with high ACTH level, but normal electrolyte 17, Hydroxyprogesterone, aldosterone, renin, androgen. Familial Glucocorticoid Deficiency was diagnosed, and maintenance dose of hydro cortisol was started, and patient pigmentation was improved few week latter.

Progressive Cribriform and Zosteriform Hyperpigmentation along with Vitiligo

Background: Progressive cribriform and zosteriform hyperpigmentation (PCZH) is a disorder of pigmentation. Although several cases of PCZH have been reported, cases that associated with vitiligo have not been published in the past. Aim: We report the case to reveal the interesting mosaicism reflecting on the skin. Case Presentation: This case presents a phenomenon of the coexistence of hyperpigmentation and depigmentation arranged in unilateral and symmetric distribution in one patient. Conclusion: The aetiology of the pigmental disorders is still unknown. The linear nature of the pigmented bands probably reflects the clonal migration and proliferation of embryonic melanoblasts, so somatic mosaicism that develops during embryogenesis appears to be the underlying aetiology, which is leading to proliferation and migration of two mixed populations of melanocytes with different potential for pigment production.