Amyloidosis Cutis Dyschromica, a RareOya Kuseyri, MD, Cause a Dorothea Haas, MD, ofa Nina Hyperpigmentation:Lang, MD, b Knut Schäkel, MD, b Markus Bettendorf, MDa a New Case and Literatureabstract Review Amyloidosis cutis dyschromica is a rare form of primary cutaneous amyloidosis without systemic involvement and characterized by asymptomatic, progressive hyper- and hypopigmentation. We present the first case of a patient with amyloidosis cutis dyschromica diagnosed previously elsewhere as having Addison disease with generalized hyperpigmentation of the skin. This case suggests that in patients presenting with asymptomatic cutaneous dyschromia a skin biopsy for histopathological examination should be considered. aDepartment of General Pediatrics and Division of Pediatric Endocrinology and Diabetes, University Children’s Hospital Heidelberg, Heidelberg, Germany; and bDepartment of Dermatology, University of Heidelberg, Heidelberg, Germany Characteristic skin signs can be helpful members with similar symptoms. Dr Kuseyri took care of the patient and drafted in clinical differential diagnostic The patient had no history of the initial manuscript; Drs Haas and Bettendorf approaches. Dermatological findings photosensitivity or inflammatory skin took care of the patient and critically reviewed can occur as part of a systemic disease. and revised the manuscript; Drs Lang and Schäkel disease or of a skin disorder. Primary provided consultation and critically reviewed the cutaneous amyloidosis (PCA) is manuscript; and all authors approved the final Hyperpigmentation appeared initially manuscript as submitted. defined as cutaneous amyloidosis after a febrile infection with vomiting DOI: 10.1542/peds.2016-0170 in the absence of other systemic and diarrhea at the age of 1 year. and dermatological manifestations. Primary adrenal insufficiency was Accepted for publication Nov 7, 2016 Amyloidosis cutis dyschromica suspected and the patient received Address correspondence to Oya Kuseyri, MD, (ACD) is a rare form of PCA. The main hormone substitution therapy with Department of General Pediatrics and Division of cutaneous feature is generalized Pediatric Endocrinology and Diabetes, University hydrocortisone, initially intravenously Children’s Hospital Heidelberg, Im Neuenheimer hyper- and hypopigmentation. and over the next years orally. No Feld 430, D-69120 Heidelberg, Germany. E-mail: oya. To date only 49 cases have been substitution of mineralocorticoids was [email protected] described. Hereby we report, to our performed. PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, knowledge, the first patient with 1098-4275). ACD assessed elsewhere as having Because the skin abnormalities did Copyright © 2017 by the American Academy of hyperpigmentation due to primary not improve during hormone therapy, Pediatrics adrenal insufficiency. laboratory evaluation of adrenal FINANCIAL DISCLOSURE: The authors have CASE DESCRIPTION function was performed at the age indicated they have no financial relationships of 8 years and revealed normal relevant to this article to disclose. glucocorticoid and mineralocorticoid FUNDING: No external funding. A 9-year-old boy from Libya secretions. For further investigation, POTENTIAL CONFLICT OF INTEREST: The authors presented with asymptomatic a skin biopsy was taken revealing have indicated they have no potential conflicts of hyperpigmentation beginning on the hyperkeratosis, mild acanthosis, interest to disclose. trunk (Fig 1 A and C) and progressing moderate irregular elongation of over almost the whole body including rete ridges with focal fusion, and To cite: Kuseyri O, Haas D, Lang N, et al. Amyloido- the nails (Fig 1B). Hair, teeth, and oral mild focal hydropic degeneration of sis Cutis Dyschromica, a Rare Cause of Hyper- mucosa were unaffected. Systemic the basal layer. The papillary dermis pigmentation: a New Case and Literature Review. examination was normal. The patient revealed deposition of amyloid Pediatrics. 2017;139(5):e20160170 was born to healthy consanguineous (confirmed by positive Congo red parents. There were no family staining) as globules and mild Downloaded from www.aappublications.org/news by guest on September 23, 2021 PEDIATRICS Volume 139, number 5, May 2017:e20160170 CASE REPORT superficial perivascular infiltrates of lymphocytes and melanophages. Hormone substitution was discontinued thereafter. One year later, the patient presented to our hospital for further diagnostic workup. Laboratory evaluations including whole blood cell count, serum electrolytes, urine analysis, renin, adrenal androgens, adrenal, pancreatic and thyroid antibodies, cortisol, and corticotropin 24-hour profiles, as well as corticotropin- releasing hormone stimulation test, were completely normal. Abdominal ultrasonography did not reveal any pathology. In dermatologic consultation, the skin findings were described as mottled hyper- and hypopigmentation. Based on the clinical findings and histopathological reevaluation of the skin biopsy, the FIGURE 1 diagnosis of ACD was established. A, Hypopigmentated macules on a background of hyperpigmentation on the chest. B, Hyperpigmen- Primary adrenal insufficiency tation of nails. C, Mottled hyper- and hypopigmentation. was excluded. Photoprotection and a follow-up examination of adrenal function after 1 year were recommended. areola, scrotal region, lips, and oral 4. Focal subepidermal amyloid DISCUSSION mucosa, as well as pigmentation of deposition. the linea alba and longitudinal2 lines in the nails can appear. Sites that are Our patient fulfilled all these criteria. exposed to sunlight and pressure are Laboratory and radiologic findings Primary adrenal insufficiency, prominently affected. did not reveal any abnormalities or Addison disease, describes a indicating systemic amyloidosis. condition of deficient production In addition, patients having of adrenal cortical hormones. Addison disease may present other The pathogenesis of ACD is unknown Patients present with nonspecific manifestations of autoimmune to date. A hypersensitivity to damage symptoms such as fatigue, malaise, endocrinopathies, such as by UV-B light with possible DNA 3 repair defects has been suggested. abdominal pain,1 weight loss, nausea, hypoparathyroidism, pernicious and vomiting. Hypotension and anemia, and vitiligo. However, there are reported cases hyperpigmentation are typical of no history of sun exposure and PCA is a chronic pruritic skin physical signs. skin findings being pronounced5,6 in disorder with characteristic amyloid nonsun-exposed skin areas. In Addison disease, deposits in the papillary dermis. ACD, The occurrence of familial cases hyperpigmentation, resulting from a rare form of PCA, was described 3, 4 and prepubertal onset suggest a6– 8 elevated cosecretion of corticotropin by Morishima and is characterized genetic etiology of the disorder, and melanocyte stimulating by the presence of the following but the molecular basis has not been hormone, presents as uniform features: identified so far. pigmentation. Hyperpigmentation usually precedes other symptoms 1. Reticular hyperpigmentation with In our case, initially described of the disease and occurs at the hypopigmented macules almost all as hyperpigmentation, the skin extensor surfaces, elbows, knees, over the body; findings revealed reticulate acral skin creases, at preexistent nevi 2. Little or no itching; hyperpigmentation with and areas of scarring formed after the hypopigmented spots, indicating a onset of the disease. Darkening of the 3. Onset before puberty; and dyschromia. Downloaded from www.aappublications.org/news by guest on September 23, 2021 e2 KUSEYRI et al FIGURE 2 Differential diagnoses of acquired hyperpigmentation. LAMB, lentigines, atrial myxomas, mucocutaneous myxomas and blue nevi; LEOPARD, lentigines, electrocardiogram abnormalities, ocular hyperteleorism, pulmonary stenosis, abnormal genitalia, retardation of growth, deafnes; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy or M proteins, skin abnormalities. On one hand, there are numerous in infancy and early childhood, as histopathological examination of a differential diagnoses of acquired well as evidence of development of skin biopsy may point the way ahead. hyperpigmentation including skin cancers during the first decade If focal amyloid deposits in papillary amyloidosis (Fig 2). In ACD of life. Poikilodermalike amyloidosis dermis are substantiated and dyschromia is present. Dyschromia is associated with photosensitivity, systemic amyloidosis is excluded, the is the coexistence of macular short stature, blister formation,3, 8 and diagnosis of ACD is confirmed. hyper- and hypopigmentation. In palmoplantar hyperkeratosis. ABBREVIATIONS Addison disease, hyperpigmentation In the literature, there is only 1 case is the sole dermatological finding. of ACD accompanying generalized In addition, the distribution of 10 morphea. No systemic involvement ACD: amyloidosis cutis pigmentary changes in Addison was described in any of the reported dyschromica disease is characteristic as it 5 cases of ACD. PCA: primary cutaneous includes the mucous membranes, amyloidosis palmoplantar skin, and the acral Several therapeutic options for skin creases, a finding not reported ACD are reported, such as topical corticosteroids, keratolytics, dimethyl in ACD. The skin findings in our REFERENCES patient did not reveal uniform sulfoxide, UV-B and psoralen–UV-A hyperpigmentation, but dyschromia phototherapy, dermabrasion, 2 1. Hsieh S,