Hypopigmented Macules Research Articles

A case of familial progressive hyperpigmentation with or without hypopigmentation presenting with hypopigmented striae along the lines of Blaschko.

Familial progressive hyperpigmentation with or without hypopigmentation (FPHH) is an autosomal dominant disorder characterized by widespread skin hyperpigmentation, café-au-lait spots, and hypopigmented circular macules, resulting from KITLG variants. KITLG, expressed by keratinocytes, binds to KIT on melanocytes, stimulating melanogenesis. Disturbances in the KITLG-KIT interaction result in diffuse hyperpigmentation in FPHH. However, the mechanisms behind hypopigmented macule formation remain unclear. This report presents a unique FPHH case in a patient with a novel KITLG mutation (Ser78Leu). Notably, the patient showed multiple hypopigmented macules and striae along the lines of Blaschko. Digital polymerase chain reaction analysis of the DNA from skin and blood tissues indicated a copy-neutral loss of heterozygosity at the KITLG locus, only in the hypopigmented macule. These findings suggest that the hypopigmented macules might result from revertant mosaicism. Conversely, café-au-lait spots do not follow the lines of Blaschko and can superimpose on the hypopigmented striae, indicating a distinct pathogenesis. This case contributes to the understanding of the genetic mechanisms in FPHH.

Multiple café-au-lait macules, axillary freckling, and hypopigmented macules in a child.

Multiple café-au-lait macules, axillary freckling, and hypopigmented macules in a child.

Evaluation of diagnostic accuracy of dermoscopy in some common hypopigmented skin diseases.

Diagnosis of cutaneous hypopigmentation can sometimes be challenging. Dermoscopy may play a role in identifying hypo or-depigmented dermatoses. The aim was to investigate which dermoscopic criteria represent potent indicators for the diagnosis of vitiligo, nevus depigmentosus, pityriasis alba, hypopigmented pityriasis versicolor, idiopathic guttate hypomelanosis, hypopigmented mycosis fungoides (MF), lichen sclerosus et atrophicus and ash leaf hypopigmented macules of tuberous sclerosis, and evaluate their diagnostic accuracy. 168 individuals diagnosed with one of these hypopigmented disorders were evaluated for the presence or absence of predetermined dermoscopic criteria. Evaluation of dermatoscopic characteristics in each condition and analysis for sensitivity and specificity of dermatoscopic diagnosis in these hypopigmented lesions was performed. The starburst pattern, micro-koebnerization, and trichrome pattern were unique to vitiligo diagnosis. Vitiligo had higher comet-tail appearance, perifollicular pigmentation, and perilesional hyperpigmentation than other hypopigmented illnesses. Other hypopigmented lesions had greater incidence of amoeboid pattern, faint or diminished pigment network, islands of pigmentation, ill-defined boundaries, pseudopods, and widespread scaling than vitiligo. Finally, perifollicular scaling, comedo-like openings, blue-gray specks, and fibrotic regions excluded vitiligo. Dermoscopy can help identify common hypopigmented skin lesions and reduce the need for skin biopsy. Nevus depigmentosus, pityriasis alba and idiopathic guttate hypomelanosis were the top three hypopigmented dermatoses that could be diagnosed by dermoscopy with 100% sensitivity. Vitiligo was in the second rank (94.7%), followed by lichen sclerosis et atrophicus (93.3%) then hypopigmented MF at 81.2% sensitivity. Dermoscopy sensitivity was lowest in pityriasis versicolor and ash leaf macules of tuberous sclerosis (52.6% and 46.7%, respectively).

Bullous Drug Eruption.

A 63-year-old woman presented at our emergency department with a disseminated dermatosis that developed after undergoing a cardiac catheterization procedure. Her past medical history included an end-stage renal disease undergoing hemodialysis. Clinical examination revealed erosions and hemorrhagic crusts located on her lips and along the arteriovenous fistula. Additionally, we observed five hyperpigmented macules on her left hand's dorsum and palm and multiple hypopigmented macules in the genital area. Upon medical record review, we discovered the occurrence of prior bullous eruptions following contrast administration. A fixed drug eruption (FDE) due to radiocontrast was diagnosed based on clinical history, clinical examination, eruption timeframe, and positive drug provocation test. Intravenous contrast media reactions can be immediate or delayed, with delayed hypersensitivity reactions (DHR) occurring one hour to seven days post-administration. DHRs often present as maculopapular rashes. FDEs are rare. Skin tests are used to identify culprit agents. Ideally, intradermal tests, with delayed readings, and patch tests are combined for optimal sensitivity. Despite lacking standardized protocols, premedication with corticosteroids may mitigate reaction severity.

Pitiriasis Versikolor

Pityriasis versicolor is an infectious disease that arises due to decreased immunity and is chronic. This disease is caused by the fungus Malassezia sp. which is characterized by hypopigmented or hyperpigmented macules, which can even be accompanied by erythematous and smooth scales. Infection occurs more often in areas with relatively higher temperatures and humidity. Pityriasis versicolor has a worldwide prevalence of up to 50% in tropical countries and 1.1% in cold climates. The incidence of pityriasis versicolor is the same in all races, but is more frequently seen in dark-skinned individuals due to changes in skin pigmentation. This case report describes a 10 year old girl who came with complaints of white spots appearing on her face for 8 months. The initial appearance of the spots is accompanied by itching when sweating. Dermatological examination revealed multiple hypopigmented macules of lenticular to nummular size with well-defined borders with fine scales. On examination with 20% KOH, grouped spores and short hyphae appear like spaghetti and meatballs. Clustered spores are a sign of colonization, while hyphae indicate infection. Pityriasis versicolor therapy consists of administering antifungals which can be done topically and systemically. Furthermore, patients are educated to always keep their skin dry, reduce activities that cause excessive sweating, and wear clothing that is not tight and absorbs sweat.

Case of Hypopigmented Mycosis Fungoides: Clinical and Pathological Discrimination from Mimicking Conditions

Background: Hypopigmented mycosis fungoides (HMF) is an uncommon variant of mycosis fungoides (MF), a cutaneous T-cell lymphoma. It presents a diagnostic challenge due to its clinical resemblance to various benign dermatological conditions. This case report highlights the importance of a comprehensive approach to diagnosis, incorporating clinical, histopathological, and immunohistochemical findings. Case presentation: A 48-year-old Indonesian woman presented with a one-year history of progressive, asymptomatic hypopigmented patches on her extremities. Initially misdiagnosed as progressive macular hypomelanosis, the patient's condition did not improve with topical treatments. Clinical examination revealed multiple hypopigmented patches and macules on both extremities, with some lesions exhibiting fine scales. Histopathological examination demonstrated atypical lymphocytes with epidermotropism and Pautrier's microabscesses. Immunohistochemical staining confirmed the presence of CD3+ T-cells, leading to the diagnosis of HMF. Conclusion: HMF can mimic various dermatological conditions, making diagnosis challenging. A thorough clinical assessment, coupled with histopathological and immunohistochemical evaluation, is crucial for accurate diagnosis and appropriate management. This case underscores the importance of considering HMF in the differential diagnosis of hypopigmented skin lesions, particularly in individuals with persistent or atypical presentations. Early recognition and intervention are essential for optimizing patient outcomes.

Erythrasmoid pityriasis versicolor: three case reports and review of the literature

Pityriasis versicolor is characterized clinically by slightly scaly, hyper- or hypopigmented macules usually located on the chest, shoulders, back and arms. Rare cases of atypical locations of pityriasis versicolor have been described, such as groins, penis and perineum. We present three cases of pityriasis versicolor located exclusively on the submammary folds, pubis and inguinal folds (the latter in an 11-year-old girl), respectively. In consideration of both location and clinical presentation of pityriasis versicolor in these three patients, we think that the diagnosis of “erythrasmoid” pityriasis versicolor is acceptable. Differential diagnosis with erythrasma must be taken into consideration. Mycological and bacteriological examinations are therefore necessary in order to make a correct diagnosis and specific therapy.

Multiple unilateral angiofibromas with a hypopigmented patch as a possible presentation of tuberous sclerosis complex (TSC)

Tuberous sclerosis complex (TSC), known as Bourneville’s disease or epiloia, is an autosomal dominant inherited disorder that may affect numerous organ systems. TSC has many forms of clinical presentation. The cutaneous features of TSC include facial angiofibromas, shagreen patches, ash leaf hypopigmented macules, periungual fibromas, forehead fibrous plaques, confetti hypopigmentation, and poliosis. Rarely, the angiofibromas in TSC have a segmental distribution. It has been suggested that the segmental expression of tuberous sclerosis may result from a postzygotic mutation. The aim of this concise communication was to describe a patient with unilateral angiofibromas associated with a hypopigmented patch. No other features of TSC were present. We think this could have been a rare presentation of TSC. Key words: Angiofibroma, Hypopigmented patch, Loss of heterozygosity (LOH), Tuberous sclerosis complex (TSC)

A Case Report on Dyschromatosis Universalis Hereditaria with Palmar Involvement

Dyschromatosis universalis hereditaria (DUH) is a rare genetic disorder characterized by hyper- and hypopigmented macules forming a reticulate pattern on the skin. This report presents an unusual case of a 14-year-old male patient with DUH involving the palms, a relatively uncommon manifestation of the condition. The patient presented with hyperpigmented lesions on the palms, which had developed over the previous eight years. Family history revealed similar pigmentary changes, suggesting a hereditary pattern. Clinical examination revealed no history of chemical or drug exposure, photosensitivity, or photophobia. Systemic evaluation was unremarkable, except for a low cortisol level of 1.12 mcg/dl (normal range: 6.2 to 19.4 mcg/dl) on the ACTH stimulation test. Skin biopsy from the left palm revealed diffuse hypermelanosis confined to the basal cell layer and occasionally extending to the lower third of the epidermis. Additionally, increased collagenization was observed in the deep dermis. Based on these findings, a diagnosis of DUH was established. The patient was initiated on long-term hydrocortisone therapy for cortisol hormone replacement. This case highlights the rare occurrence of palmar involvement in DUH and underscores the importance of thorough clinical evaluation and histopathological examination in establishing an accurate diagnosis. DUH is an uncommon genodermatosis, and reports of palmar involvement are scarce in the literature. This case contributes to the existing knowledge about the varied clinical presentations of DUH and emphasizes the need for increased awareness among clinicians

Monitoring the Long-Term Effectiveness of Miltefosine in Indian Post-Kala-Azar Dermal Leishmaniasis.

Post-kala-azar dermal leishmaniasis (PKDL), the dermal sequel to visceral leishmaniasis (VL), is characterized by hypopigmented macules (macular) and/or papules and nodules (polymorphic). Post-kala-azar dermal leishmaniasis plays a significant role in disease transmission, emphasizing the need for monitoring chemotherapeutic effectiveness. Accordingly, this study aimed to quantify the parasite burden in PKDL patients after treatment with miltefosine by a quantitative polymerase chain reaction (qPCR). A Leishmania kinetoplastid gene-targeted qPCR was undertaken using DNA from skin biopsy specimens of patients with PKDL at three time points, i.e., at disease presentation (week 0, n = 157, group 1), upon completion of treatment (week 12, n = 39, group 2), and at any time point 6 months after completion of treatment (week ≥36, n = 54, group 3). A cycle threshold (Ct) <30 was considered the cutoff for positivity, and load was quantified as the number of parasites/µg genomic DNA (gDNA); cure was considered when samples had a Ct >30. The parasite load at disease presentation (group 1) was 10,769 (1,339-80,441)/µg gDNA (median [interquartile range]). In groups 2 and 3, qPCR results were negative in 35/39 cases (89.7%) and 48/54 cases (88.8%), respectively. In the 10/93 (10.8%) qPCR-positive cases, the parasite burdens in groups 2 and 3 were 2,420 (1,205-5,661)/µg gDNA and 22,195 (5,524-100,106)/µg gDNA, respectively. Serial monitoring was undertaken in 45 randomly selected cases that had completed treatment; all cases in groups 2 or 3 had a Ct >30, indicating cure. Overall, qPCR confirmed an 89.2% cure (as 83/93 cases showed parasite clearance), and the persistent qPCR positivity was attributed to nonadherence to treatment or unresponsiveness to miltefosine and remains to be investigated.

Galli Galli Disease: A Challenging Diagnosis in a Bahraini Female Patient

Dowling-Degos Disease (DDD) is an inherited cutaneous disease which presents with classic and atypical cutaneous findings, including macules of hyperpigmentation and hypopigmentation in the flexural creases. A variant, termed Galli-Galli Disease (GGD), presents similarly, with the distinguishing feature of acantholysis on histology. Reports of GGD in the literature are rare, due to the infrequency of the diagnosis. This may contribute to a lack of available information and delayed diagnosis, which can result in a frustrating clinical course for patients. We present a female patient who presented with complaints of a burning sensation and painful rash for the last three years on a background of hypopigmented and hyperpigmented macules on the trunk, upper extremities and flexural creases. Comprehensive dermatopathological evaluation and clinical correlates led to the diagnosis of GGD.

Fungal coexistence in the skin mycobiome: a study involving Malassezia, Candida, and Rhodotorula

Evidence of fungal coexistence in humans points towards fungal adaptation to the host environment, like the skin. The human commensal Malassezia has evolved, especially residing in sebum-rich areas of the mammalian body where it can get the necessary nutrition for its survival. This fungus is primarily responsible for skin diseases like Pityriasis versicolor (PV), characterized by hypo or hyperpigmented skin discoloration and erythematous macules. In this manuscript, we report a 19-year-old healthy female who presented with a one-year history of reddish, hypopigmented, asymptomatic lesions over the chest and a raised erythematous lesion over the face. Upon clinical observation, the patient displayed multiple erythematous macules and erythematous papules over the bilateral malar area of the face, along with multiple hypopigmented scaly macules present on the chest and back. Based on the above clinical findings, a diagnosis of PV and Acne vulgaris (AV) was made. Interestingly, the patient was immunocompetent and didn’t have any comorbidities. Upon isolation of skin scrapings and post-culturing, we found the existence of three fungal genera in the same region of the patient’s body. We further went on to confirm the identity of the particular species and found it to represent Malassezia, Rhodotorula, and Candida. We report how Malassezia, the predominant microbial resident skin fungus, coexists with other fungal members of the skin mycobiome. This study on an applied aspect of microbiology also shows how important it is to identify the fungal organism associated with skin infections so that appropriate therapeutics can be advised to avoid cases of relapse.

Dyskeratosis congenita: beyond the triad and beyond the cause

Introduction: Dyskeratosis congenita (DC) is a rare genodermatosis caused by mutations in various genes encoding the proteins responsible for maintaining the telomere length. It is defined by the presence of three clinical features: nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. We herein report a typical case of DC with all three classical features along with pancytopenia, osteopenia, and epiphora but with no identifiable pathogenic mutations of DC-associated genes. Case presentation: Cutaneous examination revealed areas of hypopigmented and hyperpigmented macules forming a reticular pattern all over the body but mainly over the neck and upper chest, with relative sparing of the face. Skin atrophy with hypopigmentation was observed on the knuckles. The nails showed dystrophy in the form of pterygium, anonychia, and brittleness. The palms showed mild wrinkling with hypopigmented macules. Examination of the oral cavity revealed a white non-removable coating over the tongue and bilateral buccal mucosae (oral leukoplakia); the teeth were normal. Syringing of both eyes was performed by an ophthalmologist, and the patient was diagnosed with punctual stenosis (occlusion of the opening of the lacrimal canaliculus). Discussion: DC is a genodermatosis caused by germline mutations in genes encoding telomerase-associated components, shelterin proteins, and other regulators of telomere length and replication. Depending upon the gene involved, the mode of inheritance can be X-linked autosomal dominant or autosomal recessive. DC is characterized by the clinical triad of abnormal skin pigmentation, dystrophic nails, and oral leukoplakia. Patients with DC are also known to develop other rare clinical features at later stages, including epiphora, early graying of the hair, premature tooth loss, enteropathy with malabsorption, immune deficiency, esophageal stricture, cardiomyopathy, liver cirrhosis, osteoporosis and avascular necrosis of the bone. Patients with DC are predisposed to the development of malignancies, especially hematological malignancies and head/neck cancer. Management of DC involves a multidisciplinary approach and includes genetic counseling of family members at risk, regular surveillance of the patient for bone marrow failure and malignancies, and treatment of the associated features and any complications. Conclusion: Dyskeratosis congenita (DC) is a rare genodermatosis caused by mutations in various genes encoding telomerase complex. We present a typical case of DC with all three classical features but with no pathogenic mutations of existing DC-associated genes thus raising the possibility of new unidentified genes in the pathogenesis of DC.

P15 A Case of Juvenile Dermatomyositis in a 15-year old African-descent Girl

Abstract A 15-year-old female with skin of colour (SOC), was diagnosed with Juvenile dermatomyositis (JDM) following a presentation with muscle weakness, swallowing difficulties and rash. Investigations showed CK&amp;gt;1300, positive Mi-2 alpha, beta antibodies and bilateral myositis on MRI pelvis. Her skin features commenced 2 months prior to her rheumatological presentation. They included erythematous pruritic patches on the limbs, generalised hyperpigmentation of the face and trunk, hyperpigmentation of palmar creases and nail folds, flagellate hyperpigmentation of the hands &amp; arms, and hypopigmented macules with follicular sparing across the face. She also presented skin thickening over the interphalangeal joints and nail fold capillary dilatation and infarctions. Skin biopsy showed interface dermatitis, in keeping with dermatomyositis. She was managed with weaning prednisolone, methotrexate, topical tacrolimus and sunscreen. JDM is a small-vessel autoimmune vasculopathy leading to muscle inflammation and skin changes. Unlike adult-onset disease, JDM is not associated with malignancy. The typically described violaceous skin features of JDM including photosensitive rash periorbitally, and over the knees and knuckles (Gottron’s sign) may be hyperpigmented rather than erythematous in skin of colour. Additional skin features described in SOC are generalised hyperpigmentation and pigmentation in skin creases. A flagellate dermatitis is uncommon, but recognised in association with Mi-2 antibodies in JDM. TIF1 antibodies have been reported in association with hypopigmented patches which may mimic vitiligo postulated possibly secondary to interface inflammation perhaps leading to dyspigmnentation. Notably our patient was negative for TIF1. This presentation highlights some of the less commonly described skin features of dyspigmentation in JDM in SOC.

P16 Hypopigmented Mycosis Fungoides in a Caucasian child

Abstract We report a case of hypopigmented MF in an 8-year-old Caucasian boy whose skin had been managed as pityriasis alba for a number of years. On initial presentation to the emergency department, multiple non-itchy scattered hypopigmented macules were incidentally noted on the lower abdomen, groin, lateral flanks and axillae. Physical examination revealed widespread hypopigmented patches. Differential diagnoses included pityriasis alba or post inflammatory hypopigmentation secondary to atopic dermatitis. He was initially managed with mild to moderate corticosteroids and emollients, but continued to develop multiple atypical asymmetrical macules, particularly on the lower abdomen and groin. Although the skin was responsive to anti-inflammatory treatment, given the progression, a skin biopsy was requested. A lesional punch biopsy from the abdomen revealed focal lymphocyte exocytosis and interface change at the epidermis. Given the subtle findings the case was discussed at our histopathology MDT meeting. Further specialist review of the histopathology showed clinicopathological correlation in keeping with CD8+ mycosis fungoides (hypopigmented variant). He is currently managed with regular potent topical steroids, 0.1% topical tacrolimus. TL01 phototherapy has been suggested. Juvenile onset MF constitutes hypopigmented, poikilodermatosis, pityriasis lichenoides-like, folliculotropic, and pigmented purpura- like presentations1. Generally there is no disease progression beyond stage 1A or 1B disease2. Hypopigmented MF is well described in black and Asian skin types but it is also important to appreciate that multiple reoccurring atypical hypopigmented patches in Caucasian skin may also be a variant of hypopigmented MF.

ADAR1 gene mutations in two Chinese pedigrees with dyschromatosis symmetrica hereditaria

Introduction: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominantly inherited disease with high penetrance. Patients with DSH display a mixture of hyperpigmented and hypopigmented macules on the dorsal aspects of the extremities and freckle-like macules on the face. Case presentation: We identified mutations in two Chinese pedigrees with DSH using whole-exome sequencing (WES) and verified these mutations with PCR-Sanger sequencing. We found a previously reported mutation, c.2433_2434del (p.A813Qfs*29), in exon 7 of ADAR1 in the patient of pedigree one and a novel mutation, c.3301G&gt;T(p.V1101F), in exon 13 of ADAR1 in the patients of pedigree two. Discussion: We have identified two gene mutations, one of which may be a novel mutation. At present, the main focus is to improve the color of skin lesions. Laser therapy and sun protection can to some extent alleviate skin lesions. Conclusion: The findings of the current case have expanded the range of ADAR1 mutations associated with DSH and may be of great help for future clinical genetic counseling.

Tuberous Sclerosis or Bourneville-pringle disease: A rare case report

Introduction: Tuberous sclerosis or Bourneville’s disease is rare autosomal dominant neurocutaneous. Which is characterized by Skin changes, neurological issues, and the development of hamartomas in several organs that cause morbidity and mortality. The gingival hyperplasia, fibromas, hypopigmented lesion’s and enamel hypoplasia are the most typical features of presentation. The case report emphasises on the crucial clinical characteristics, radiographic characteristics, and laboratory abnormalities of Tuberous Sclerosis assisting in the early detection and treatment of such a rare illness. Case presentation: In this report, we present a case of tuberous sclerosis in a 25-year- old female who displayed abnormal body movement along with a hypopigmented macule, ash leaf spots, periungual fibroma, gum hyperplasia, and hematuria with pain in the bilateral flank. Conclusion: Our aim is to raise awareness for tuberous sclerosis by using this instance to highlight the disease's rarity and the difficulty in identifying and treating cases like this.

Generalized hyperpigmented and hypopigmented macules and papules.

A 49-year-old White woman with an unremarkable medical history presented with mildly pruritic hyperpigmented and hypopigmented macules and papules scattered across her face, trunk and limbs since her twenties.

P30 An unusual infective cause of inflammatory arthritis

P30 An unusual infective cause of inflammatory arthritis

Multi-dimensional Insight into the Coexistence of Pathogenic Genes for ADAR1 and TSC2: Careful Consideration is Essential for Interpretation of ADAR1 Variants.

Aicardi-Goutières syndrome 6 (AGS6) is a serious auto-immunization-associated acute neurologic decompensation. AGS6 manifests as acute onset of severe generalized dystonia of limbs and developmental regression secondary to febrile illness mostly. Dyschromatosis symmetrica hereditaria (DSH), as pigmentary genodermatosis, is a characterized mixture of hyperpigmented and hypopigmented macules. Both AGS6 and DSH are associated with ADAR1 pathogenic variants. To explore the etiology of a proband with developmental regression with mixture of hyperpigmentation and hypopigmentation macules, we used the trio-WES. Later, to clarify the association between variants and diseases, we used guidelines of ACMG for variants interpretation and quantitative Real-time PCR for verifying elevated expression levels of interferon-stimulated genes, separately. By WES, we detected 2 variants in ADAR1 and a variant in TSC2, respectively, were NM_001111.5:c.1096_1097del, NM_001111.5:c.518A>G, and NM_000548.5:c.1864C>T. Variants interpretation suggested that these 3 variants were both pathogenic. Expression levels of interferon-stimulated genes also elevated as expected. We verified the co-occurrence of pathogenic variants of ADAR1 and TSC2 in AGS6 patients with DSH. Our works contributed to the elucidation of ADAR1 pathogenic mechanism, given the specific pathogenic mechanism of ADAR1, and it is necessary to consider with caution when variants were found in ADAR1.