Graham-Little Piccardi-Lasseur syndrome is a rare dermatosis that affects the hair follicles throughout the body and often presents with a progressive cicatricial alopecia of the scalp that is unresponsive to medical therapy. While treatment options are limited, prompt recognition through a careful physical exam aided by dermoscopy can facilitate early intervention. Here we present a patient with GLPLS, discuss pertinent morphologic and dermoscopic findings, and review the current literature. J Drugs Dermatol. 2022;22(2):210-216. doi:10.36849/JDD.6926.

Haematobia irritans exigua, commonly known as buffalo fly, is the major hematophagous ectoparasite of north Australian cattle herds. Lesions associated with buffalo fly infestation are generally alopecic, hyperkeratotic, or scab encrusted wounds with variable hemorrhagic ulceration. Buffalo flies can transmit a filarial nematode, Stephanofilaria sp., which has been implicated in the pathogenesis of buffalo fly lesions, but Stephanofilaria infection has not been detected in all lesions suggesting that other causal factors may be involved. This study characterized the pathology of buffalo fly lesions to identify the role of Stephanofilaria in lesion development, as well as to identify other potential agents. Lesion biopsies were collected from north and south Queensland and tested for the presence of Stephanofilaria by qPCR. Each lesion was scored grossly (0-4) for hemorrhage, ulceration, exudation, and alopecia. Lesions were also scored microscopically (0-4) for epidermal and dermal damage and inflammatory characters. Stephanofilaria infection was detected in 31% of lesion biopsies. Grossly, Stephanofilaria-infected lesions had significantly larger lesion area and higher scores for alopecia and hyperkeratosis than lesions where no nematodes were found (P < 0.05). Histologically, epidermal, dermal, and adnexal damage was significantly higher in Stephanofilaria infected lesions than lesions without nematodes. Eosinophils, macrophages, and lymphocytes were significantly more abundant in Stephanofilaria positive lesions as compared to negative lesions. This study also noted bacterial infection with colonies of coccoid bacteria, observed in skin sections from 19 lesions. Grossly, lesions with bacterial infection had significantly higher ulceration scores compared to Stephanofilaria positive lesions, and histologically epidermal disruption was significantly greater in bacteria-infected lesions. We found no evidence of bacteria or Stephanofilaria infection in 49% of the lesions assessed and tissue damage patterns and eosinophilic inflammation suggested hypersensitivity to buffalo fly feeding as a possible cause of these lesions. These findings suggest that although the presence of Stephanofilaria infection may increase the severity of lesion pathology, it is not essential for lesion development. These outcomes also suggest a potential role of bacteria and hypersensitivity in pathogenesis of some lesion. A better understanding of buffalo fly lesion etiology will contribute to the optimal treatment and control programmes.

Alopecia areata is an autoimmune disease resulting in non-scarring hair loss. Alopecia areata can progress to become alopecia totalis (loss of hair from the entire scalp) or alopecia universalis (loss of hair form the entire body), with the progression estimated to range from 7% to 30%. There are no universally proven therapies that both induce and sustain remission, and furthermore, the course of alopecia areata tends to be unpredictable, with ~80% of patients achieving spontaneous remission within 1 year. We herein present the case of a 61-year-old female who presented with a 20-year history of alopecia universalis, and biopsy confirmed widespread granuloma annulare. Hydroxychloroquine was initiated to treat her granuloma annulare, with subsequent significant hair regrowth on her scalp, eyebrows, eyelashes, and arms. A review of the literature is presented showing that hydroxychloroquine has variable success in treatment of alopecia areata, alopecia totalis, and alopecia universalis.

Ovarian hyperthecosis or ovarian stromal hyperplasia is a non-neoplastic functional disorder resulting from the presence of luteinized thecal cells within a hyperplastic ovarian stroma. The condition is more common in postmenopausal women than in those of reproductive age and leads to substantial clinical and laboratory alterations, principally androgenetic alopecia, progressive hirsutism, and elevated testosterone levels. Investigation should include clinical evaluation, laboratory tests, and imaging tests to differentiate between the principal diagnostic hypotheses. The gold standard for diagnosis is histopathology of the ovarian tissue. The present case report describes a woman being followed up as an outpatient at the Santa Casa de Misericórdia Hospital in Vitória, Brazil. The objective in publishing this case report is to add to available data on ovarian hyperthecosis, thus contributing towards improving timely diagnosis and treatment. Early diagnosis and treatment would ensure better quality of life for patients with this condition and better physical and mental health. Moreover, these data should be useful both for the medical community and for future research into this disease.

Minoxidil has been used as an effective and cost-efficient topical treatment for androgenic alopecia. However, due to its poor water solubility, commercially available formulations contain alcohol and propylene glycol in a concentration that causes skin reactions such as irritation and dryness. Therefore, nanotechnology-based formulations can offer an alternative that might increase penetration and deposition of the drug in the skin while minimizing its adverse reactions. Minoxidil cubosomes (MXD-CUB) were prepared by melt dispersion emulsification technique according to full 23 factorial design. Three Independent variables, namely, the dispersed phase concentration, glyceryl monooleate: Poloxamer 407 ratio and Tween 80 concentration were tested. Particle size, polydispersity index and the zeta potential were the dependent variables. The optimized formula was investigated by transmission electron microscopy, x-ray diffractometry and in vitro release test. In vivo study included Draize test, histopathological examination, hair re-growth efficacy and confocal laser scanning microscopy (CLSM). Particle size, zeta potential and polydispersity index of the optimal MXD-CUB were measured to be 131.10±1.41 nm, -23.5±0.42 mV and 0.185±0.0, respectively, and its entrapment efficiency was 80.4±4.04 %. Draize test and histopathological testing proved safety and tolerability of MXD-CUB. In vivo hair regrowth study revealed greater hair growth boosting effect of the prepared cubosomes compared to minoxidil solution. CLSM proved superior penetration and retention of rhodamine B-loaded cubosomes in the skin compared to rhodamine B solution. Therefore, MXD-CUB can be a safe and effective dosage form of minoxidil that overcome the drawbacks of the commercial formulations.

Chemotherapy is one of the widely used anticancer treatments that involves the use of powerful cytotoxic drugs to stop tumor growth by targeting rapidly dividing cells through various mechanisms, which will be elucidated in this review. Introduced during the early twentieth century, chemotherapy has since lengthened the longevity of innumerable cancer patients. However, the increase in lifespan is at the expense of quality of life as patients are at risk of developing short-term and long-term side effects following chemotherapy, such as alopecia (hair loss), chemotherapy-induced peripheral neuropathy, chemotherapy-induced nausea and vomiting, cardiotoxicity, diarrhea, infertility, and chemo brain. Currently, a number of these chemotherapy-induced adverse effects are managed through supportive care and approved treatments, while the rest of the side effects are unavoidable. Hence, chemotherapeutic drugs associated with inevitable side effects are only administered when their therapeutic role outweighs their chemotoxicity, thus severely limiting the potency of chemotherapy in treating malignancy. Therein, the potential approaches to alleviating side effects of chemotherapy ranging from pharmaceutical drugs to alternative therapies will be discussed in this review in hopes of increasing the tolerance and effectiveness of future chemotherapeutic treatments.

Zinc is a necessary trace element and an important constituent of proteins and other biological molecules. It has many biological functions, including antioxidant, skin and mucous membrane integrity maintenance, and the promotion of various enzymatic and transcriptional responses. The skin contains the third most zinc in the organism. Zinc deficiency can lead to a range of skin diseases. Except for acrodermatitis enteropathic, a rare genetic zinc deficiency, it has also been reported in other diseases. In recent years, zinc supplementation has been widely used for various skin conditions, including infectious diseases (viral warts, genital herpes, cutaneous leishmaniasis, leprosy), inflammatory diseases (hidradenitis suppurativa, acne vulgaris, rosacea, eczematous dermatitis, seborrheic dermatitis, psoriasis, Behcet's disease, oral lichen planus), pigmentary diseases (vitiligo, melasma), tumor-associated diseases (basal cell carcinoma), endocrine and metabolic diseases (necrolytic migratory erythema, necrolytic acral erythema), hair diseases (alopecia), and so on. We reviewed the literature on zinc application in dermatology to provide references for better use.

We report a case of a woman in her 30s who struggled with a life-long history of trichotillomania (TTM; hair-pulling disorder), which was unsuccessfully treated with behavioural therapy and selective serotonin reuptake inhibitors. In addition to TTM, our patient had a history of chronic migraine which brought her to our clinic, and treatment with onabotulinumtoxinA (OBTA) was initiated per the Phase III REsearch Evaluating Migraine Prophylaxis Therapy protocol. After experiencing improvement with migraine symptoms, she began off-label treatment with OBTA for her TTM with 45 units being injected, 5 units per site, in diffuse regions of her scalp, primarily on the affected areas of TTM-induced alopecia. The patient reported marked improvement in her TTM signs and symptoms, which resulted in hair regrowth as early as the first follow-up visit 12 weeks post-treatment initiation. Treatment effects were maintained, and additional hair regrowth was observed at the 1-year post-treatment visit, which equated to four cycles of treatment.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is characterized by failure to thrive, severe chronic diarrhea, neonatal type 1 diabetes or thyroiditis, and eczematous dermatitis. We report a patient with infantile onset IPEX syndrome who developed vitiligo, alopecia, and chronic diarrhea. Awaiting stem cell transplant, he had multiple episodes of sepsis and succumbed at the age of 10 months. The constellation of symptoms is important to prompt clinicians to suspect this rare syndrome as early hematopoietic stem cell transplantation is the only cure for IPEX patients.

Objective: To compare the efficacy, safety, and influencing factors among children with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B (CHB) who received short-term therapy with pegylated interferon alfa-2a (Peg-IFNα-2a) or continuous therapy with entecavir (ETV). Methods: Quantitative data were compared using analysis of variance to compare the differences between groups. Enumeration data were compared by χ2 test (or Fisher's exact test). Univariate and multivariate logistic regressions were used to analyze the influencing factors. Results: Peg-IFNα-2a, ETV, and untreated group had HBsAg clearance rates of 46.2%, 5.3%, and 0 after 52 weeks of therapy, respectively. HBsAg clearance in the patients' group with Peg-IFNα-2a and ETV was all accompanied by anti-HBS positive conversion, and the difference was statistically significant (χ2=13.616, P=0.001). Peg-IFNα-2a group was followed-up for 104 weeks. Peg-IFNα-2a, ETV, and the untreated group had HBsAg clearance rates of 46.2%, 10.5%, and 0%, respectively, and the differences were statistically significant (χ2=11.056, P=0.004). Only one of the two children with HBsAg clearance in the ETV group had achieved anti-HBs antibodies, and the difference was statistically significant (χ2=13.616, P=0.001). Univariate and multivariate logistic regression analysis showed that HBsAg clearance was associated with age and antiviral therapy. During treatment, adverse events such as fever (n=4, 30.8%), rash (n=4, 30.8%), fatigue (n=1, 7.7%), leukopenia (n=7, 53.8%), arthritis (n=1, 7.7%), and alopecia (n=3, 23.1%) were observed in the Peg-IFNα-2a group, while none were observed in the ETV group. Conclusion: Peg-IFNα-2a antiviral therapy produced higher HBsAg clearance than ETV in five-year-old and younger children with HBeAg-positive CHB, while ETV had fewer adverse events and was safer than Peg-IFNα-2a.

This study, which aimed to identify distress by sites of hair loss and psychosocial stressors for a pediatric alopecia areata population, enrolled 50 patients (32 females, 18 males, ages 7-17 years) from pediatric dermatology clinics, including a monthly hair disease clinic. Patients completed a 47-question survey. Scalp hair loss was rated as often or always bothersome in 34.7%; eyebrow loss in 24.3%; and eyelash loss in 21.6%, and 6 patients (12%) discontinued a social activity due to hair loss. Referral to behavioral/mental health specialists should be considered to improve psychosocial outcomes.

A woman in her 50s presented with total scarring ulcerated alopecia evolving for 10 years, and a recent budding tumour on the lower lip. Clinical examination revealed an associated exfoliated and infiltrated erythroderma with ulcerated cutaneous tumours of the legs, palmoplantar hyperkeratosis, hepatosplenomegaly and diffuse lymphadenopathies.Dermatoscopy of the scalp, leg tumours and infiltrated skin showed a typical yellowish background overlaid by arborescent vessels and whitish areas. Cutaneous biopsies of the same areas found sarcoidotic granulomas. Lip biopsy found an associated well-differentiated squamous cell carcinoma. Investigations confirmed the diagnosis of systemic sarcoidosis with an elevated converting enzyme level, mediastinal calcified lymphadenopathies in CT scan and deep localisations in positron emission tomography scan (thyroid, lymph nodes, mediastinum, liver, spleen and adrenal glands).The patient was treated with oral prednisone for sarcoidosis and intramuscular bleomycin followed by surgery and radiotherapy for squamous cell carcinoma. Sarcoidotic lesions healed, but a recurrence of her carcinoma led to death.

Start codon mutations in ubiquitin ligase Kelch-like protein 24 (KLHL24) lead to a gain-of-function mutant KLHL24-ΔN28, which mediates the excessive degradation of keratin 15, desmin, and keratin 14, resulting in alopecia, cardiopathy, and epidermolysis bullosa syndrome (ACES). ACES patients normally present atrophic scars after wounds heal, which is rare in KRT14-related epidermolysis bullosa (EB). The mechanisms underlying the formation of atrophic scars in EB of ACES patients remain unclear. This study demonstrated that KLHL24-ΔN28 impaired skin wound healing by excessively degrading vimentin. Heterozygous Klhl24c.3G>T knock-in mice displayed delayed wound healing and decreased wound collagen deposition. We identified vimentin as a unreported substrate of KLHL24. KLHL24-ΔN28 mediated the excessive degradation of vimentin, which failed to maintain efficient fibroblast proliferation and activation during wound healing. Furthermore, by mediating vimentin degradation, KLHL24 can hinder myofibroblast activation, which attenuated bleomycin-induced skin fibrosis. These findings demonstrated the function of KLHL24 in regulating tissue remodeling, atrophic scarring, and fibrosis.

Age is associated with the decline of multiple organ systems. In older patients, hematological toxicities associated with chemotherapy are often dose limiting, impairing dose intensity and treatment efficacy. Contrary to the classical path using growth factors to activate tissue regeneration, a novel strategy is emerging to prevent chemotherapy toxicity that involves temporary cell-cycle arrest of normal cells, such as hematopoietic or epithelial precursors. This proactive approach may allow the sparing of the stem cell reserve of these tissues. Two molecules are included in this new category, trilaciclib and ALRN-6924, which induce cell-cycle arrest by two different pathways. Previous approaches, such as the use of myelopoietic growth factors, were reactive and they might even have accelerated the depletion of stem cells by enhancing the commitment of these elements. Trilaciclib causes cell-cycle arrest by CDK 4/6 inhibition and ALRN-6924 by p53 activation. In a pooled analysis of three randomized phase II studies of patients with small cell lung cancer, trilaciclib prevented neutropenia, thrombocytopenia, and anemia. Similar chemoprotective results were observed with ALRN-6924 in an open-label phase Ib study of patients with p53-mutated small cell lung cancer. Trilaciclib is now approved as a myelopreservation agent in patients with extensive-stage small cell lung cancer. ALRN-6924 is currently in phase Ib clinical development in patients with p53-mutated cancer. In addition to preserving the normal hemopoietic pool, these drugs promise to preserve the stem cell reserve of other normal tissues with high turnover, preventing potentially other dose-limiting toxicities, such as mucositis and diarrhea. An "ex vivo" study provided early evidence that ALRN-6924 may prevent chemotherapy-induced alopecia. By affording protection from multiple toxicities with a single drug, trilaciclib and ALRN-6924 have the potential to transform the current standards of supportive care for oncology patients and may prevent the depletion of tissue stem cells already compromised with age.