Acquired reactive perforating collagenosis triggered by trauma with eosinophilia: a case report and literature review.

Acquired reactive perforating collagenosis (ARPC) is a rare dermatological disorder condition defined by the perforation of altered collagen fibers through the epidermis. The presence of underlying conditions such as diabetes or renal disease is helpful in the ARPC diagnosis. Although skin rashes related to ARPC have been reported, the exact causative factors and mechanisms remain unclear. Here, we present a unique case of ARPC triggered by trauma in a 67-year-old male without concurrent systemic alterations. The diagnosis of ARPC with eosinophilia was made following comprehensive diagnostic testing, including clinical presentation, histological results, and blood tests, ruling out other possible diseases. Intriguingly, the histopathological examination revealed collagen penetration into the epidermis at different tissue sections. In addition, we reviewed existing literature on ARPC, which documented the causation. To help confirm the diagnosis, clinicians have to pay attention to traumatic triggers for ARPC and its rare manifestation with eosinophilia.

An Unusual Case of Fever in Paralytic Ileus.

Still's disease is frequently a condition of exclusion for patients with an unidentified cause of fever. Accompanying symptoms typically include fever, arthralgia, and a transient skin rash. The underlying pathophysiology indicates an autoimmune origin. Diagnosis is primarily clinical, often utilizing the Yamaguchi criteria. The case in question involves a 19-year-old male presenting with high-grade fever and paralytic ileus. The patient received intravenous glucocorticoids and cyclophosphamide, resulting in a rapid clinical improvement. During the follow-up, tofacitinib was initiated based on the clinical response observed.

Elucidating the Mechanisms Underlying Interindividual Differences in the Onset of Adverse Drug Reactions.

Idiosyncratic drug toxicities (IDTs) pose a significant challenge; they are marked by life-threatening adverse reactions that emerge aftermarket release and are influenced by intricate genetic and environmental variations. Recent genome-wide association studies have highlighted a strong correlation between specific human leukocyte antigen (HLA) polymorphisms and IDT onset. This review provides an overview of current research on HLA-mediated drug toxicities. In the last six years, HLA-transgenic (Tg) mice have been instrumental in advancing our understanding of these underlying mechanisms, uncovering systemic immune reactions that replicate human drug-induced immune stimulation. Additionally, the potential role of immune tolerance in shaping individual differences in adverse effects highlights its relevance to the interplay between HLA polymorphisms and IDTs. Although HLA-Tg mice offer valuable insights into systemic immune reactions, further exploration is essential to decipher the intricate interactions that lead to organ-specific adverse effects, especially in organs such as the skin or liver. Navigating the intricate interplay of HLA, which may potentially trigger intracellular immune responses, this review emphasizes the need for a holistic approach that integrates findings from both animal models and molecular/cellular investigations. The overarching goal is to enhance our comprehensive understanding of HLA-mediated IDTs and identify factors shaping individual variations in drug reactions. This review aims to facilitate the development of strategies to prevent severe adverse effects, address existing knowledge gaps, and provide guidance for future research initiatives in the field of HLA-mediated IDTs.

A case report of Hyper-IgD syndrome in a 5-year-old girl with recurrent fever, skin rash, and arthralgia; novel MVK mutation (C.298G>A).

Key Clinical Message: This case highlights the potential for later-onset Hyper-IgD syndrome (HIDS) even beyond infancy. Clinicians evaluating children with recurrent fever, skin rash, and arthralgia should consider HIDS in the differential diagnosis, regardless of age. Early suspicion and genetic testing can lead to a timely diagnosis and targeted therapy with Anakinra, significantly improving patient outcomes. Abstract: Hyper-IgD syndrome (HIDS) is a rare autosomal recessive autoinflammatory disorder characterized by recurrent episodes of fever, lymphadenopathy, arthralgia, diarrhea, abdominal pain, and skin rash. In this case report, we present a 5-year-old girl from Tajikistan with a mutation in the mevalonate kinase (MVK) gene, which is consistent with a diagnosis of HIDS. The clinical symptoms of the patient are described, along with immunological, hematological, and biochemical findings collected from the evaluation in the rheumatology clinic. Additionally, whole-exome sequencing revealed a heterozygous missense variation in exon 4 of the MVK gene. The diagnosis of HIDS in this case occurred at a later age than typically observed, emphasizing the importance of considering this condition even in older patients. This report highlights the broad clinical phenotype of MVK and the need for increased awareness among healthcare professionals regarding its clinical presentation and management.

Unusual Neurological Complications in a Patient With Monkeypox: A Case Report.

Monkeypox is a zoonotic disease caused by an enveloped single-stranded DNA virus that belongs to the Poxviridae family. It was first identified in humans in the 1970s. In 2022, a monkeypox outbreak spread extensively outside of endemic countries. Monkeypox infection begins with the prodromal symptoms of fever, myalgia, and lethargy, followed by the development of a characteristic maculopapular rash. In most cases, the illness is self-limiting. However, severe cases can lead to devastating neurological complications, such as encephalitis. Here, we present the case of a 31-year-old male patient with monkeypox who developed encephalomyelitis and exhibited complete neurological recovery upon treatment with pulse steroid and intravenous immunoglobulin.

Sezary Syndrome: A Case Report and Review of Current Therapeutics.

Sezary syndrome (SS) is a rare but aggressive type of cutaneous T-cell lymphoma (CTCL). Patients with SS have characteristic skin lesions (erythroderma) and a leukemic phase. The rash associated with CTCLs can often mimic common benign skin conditions such as psoriasis, atopic dermatitis, etc. and therefore can go undiagnosed until later stages. We present a case of a patient with SS who managed eczema for over one year with topical steroids before receiving a skin biopsy. Workup confirmed leukemic involvement, and the patient was started on systemic therapy with bexarotene. The patient continues to have a good response to systemic therapy. When treating patients with persistent rash of uncertain etiology and/or unresponsive to treatment, primary care physicians and internists need to consider SS/Mycosis fungoides as a possible differential and should have a low threshold to initiate early referral to dermatology for definitive diagnosis.

The use of PD-1 functional knockout rats to study idiosyncratic adverse reactions to nevirapine.

Idiosyncratic drug reactions (IDRs) are associated with significant patient morbidity/mortality and lead to considerable drug candidate attrition in drug development. Their idiosyncratic nature makes the study of IDRs difficult. In particular, nevirapine is associated with a relatively high risk of serious skin rash and liver injury. We previously found that nevirapine causes a similar skin rash in female Brown Norway rats, but these animals do not develop significant liver injury. Programmed cell death protein-1 (PD-1) is an immune checkpoint involved in immune tolerance, and anti-PD-1 antibodies have been used to treat cancer. However, they increase the risk of liver injury caused by co-administered drugs. We found that PD-1-/- mice are more susceptible to drug-induced liver injury, but PD-1-/- mice are not a good model for all drugs. In particular, they do not develop a skin rash when treated with nevirapine, at least in part because they lack the sulfotransferase in their skin that forms the reactive metabolite responsible for the rash. Therefore, we developed a PD-1 mutant (PD-1m/m) rat, with an excision in the ligand-binding domain of PD-1, to test whether nevirapine would cause a more serious skin rash in these animals. The PD-1m/m rat was based on a Sprague Dawley background, which has a lower incidence of skin rash than Brown Norway rats. The treated PD-1m/m rats developed more severe liver injury than PD-1-/- mice, but in contrast to expectations, they did not develop a skin rash. Functional knockouts provide a unique tool to study the mechanisms of IDRs.

A Case of Macrophage Activation Syndrome With Elderly Onset Still's Disease Under Tocilizumab Treatment.

Adult-onset Still's disease in older adults is referred to as elderly onset Still's disease (EOSD). Few cases of tocilizumab (TCZ) use for EOSD management have been reported. Here, we report the case of an 87-year-old Japanese woman with EOSD who was not previously taking any medication. She had fatigue, sore throat, and loss of appetite for several days and gradually experienced difficulty walking. On examination, she was found to have a fever and erythema on the buttocks and extremities. Laboratory tests revealed leukocytosis with neutrophil predominance, elevated C-reactive protein (CRP) levels, and hyperferritinemia. A contrast-enhanced computed tomography scan of the chest to the abdomen showed no abnormalities. Antimicrobial therapy was initiated; however, the fever did not resolve. On day seven, 40 mg/day prednisolone (PDN) was started for EOSD in the absence of an obvious infection or a malignancy. On day 20, the fever recurred, and the patient was started on intravenous methylprednisolone (mPDN) half-pulse therapy (500 mg/day for three days). The fever resolved, and the CRP level decreased to 1 mg/dL but did not return to normal. On day 35, the fever recurred; therefore, 320 mg of TCZ was injected intravenously, and the PDN was tapered. On day 43, the patient tested positive for cytomegalovirus (CMV) antigenemia and improved on ganciclovir. On day 70, the patient developed fever, decreased white blood cell (WBC) and hemoglobin (Hb) levels, high lactate dehydrogenase (LDH) levels, hyperferritinemia, and elevated liver enzymes. Macrophage activation syndrome (MAS) was diagnosed due to hemophagocytosis on bone marrow examination. The patient was started on pulse therapy with glucocorticosteroids and cyclosporine. The patient's fever decreased, and her WBC count and LDH level normalized. The patient continued rehabilitation for muscle weakness due to prolonged hospitalization and high-dose steroid use and was discharged from the hospital on day 150. The findings in this case suggest that the use of TCZ during the remission induction phase of EOSD may lead to MAS.

Icodextrin-induced acute generalized exanthematous pustulosis in a patient with peritoneal dialysis.

Icodextrin has been widely prescribed for peritoneal dialysis (PD) patients with inadequate ultrafiltration, but icodextrin induced acute generalized exanthematous pustulosis (AGEP) has been not well recognized in clinical practice. We described a young-aged female with IgA nephropathy and end stage kidney disease under continuous automated peritoneal dialysis. She developed skin erythema with exfoliation over the groin 7th day after initiation of icodextrin based PD dialysate. Initially, her scaling skin lesion with pinhead-sized pustules affected the bilateral inguinal folds, and then it extended to general trunk accompanied by pruritus. She was admitted because of deterioration of skin lesion on 14th day of icodextrin exposure. She was afebrile and physical examination was notable for widespread erythematous papules with pruritus extending over her groins and trunk. Pertinent laboratory examination showed leukocytosis of 18 970 cells/µL with neutrophile count of 17 642 cells/µL (92.3%), and c-reactive-protein: 3.39 mg/dL. Skin biopsy revealed multifocal sub corneal abscess with papillary dermal edema, and upper-dermal neutrophilia with perivascular accentuation, consistent with the diagnosis of AGEP. After discontinuation of PD, she underwent temporary high-flux haemodialysis with treatment of steroid and antihistamine. Her dermatologic lesion resolved without any skin sequalae completely within 4 days, and she underwent icodextrin-free peritoneal dialysis at 17th day. This case highlighted the fact that icodextrin-induced AGEP should be early recognized to avoid inappropriate management.

Longitudinal study of patients with anti-SAE antibody positive dermatomyositis: a multicenter cohort study in China.

OBJECTIVES: To describe the longitudinal study and long-term prognosis of multicentre large inception cohort of patients with anti-SAE positive DM. METHODS: We retrospectively recruited patients with anti-SAE+DM in four tertiary referral centers from China between March 2005 and December 2022. Long-term survival analysis was performed in the enrolled patients. The Myositis Damage Index (MDI) and Cutaneous Disease Area and Severity Index (CDASI) were used to evaluate the degree of different organ damage and the extent of skin rashes. Longitudinal computed tomographic (CT) patterns were analyzed. Phenotypes were characterized using unsupervised cluster analysis. RESULTS: All-cause death occurred in 10.5% (4/38) of all patients, in which three patients succumbed to malignancies at 13, 18, and 36 months. Most patients had favorable long-term outcomes, 35.3% of them were in drug-free remission. Skin rashes showed significant improvement evaluated by CDASI with time. However, damage to different systems was observed in 70.6% of the surviving patients using the MDI, which mainly consisted in skin damage, accounting for 47.1%. Nine patients with anti-SAE+DM associated interstitial lung disease (ILD) underwent repeat CT showed marked radiological improvement at 6 months or being stable after 12 months. In further, different characteristics and outcomes were also showed in three clusters identified by unsupervised analysis. CONCLUSIONS: Anti-SAE+DM is characterized with lower mortality rate and the development of malignancies being the primary cause of death. Patients who survived showed notable cutaneous damage, while the ILD tends to stabilize. Clusters identified with unsupervised analysis could assist physicians in identifying higher risk of mortality.

Cutaneous manifestations of adult-onset Still's disease: A comparative study between young-onset and elderly-onset groups.

We investigated the detailed characteristics and proportions of typical and atypical rashes in 28 patients with adult-onset Still's disease (AOSD) by retrospectively examining the clinical symptoms and pathological features. The patients consisted of six males and 22 females aged between 23 and 85 years. The skin rashes observed in the study population were as follows: (i) typical rash in six cases, (ii) atypical rash in 19, and (iii) both typical and atypical rash in three cases (in all three cases, typical rash preceded atypical rash). Furthermore, we classified atypical rashes into persistent pruritic papules and plaques (PPPP) and others. In 22 cases of atypical rashes, 10 cases had PPPP. In a comparison between young-onset (<65 years) (n = 16) and elderly-onset (≥65 years) (n = 12) AOSD cases, typical rashes were observed more frequently in the young-onset cases. Regarding atypical rashes, PPPP was significantly more common in the elderly-onset cases.

Hypothyroidism Due to Seaweed Overconsumption.

Hypothyroidism presents various symptoms, ranging from commonly observed signs, such as fatigue, cold sensation, and constipation, to rare features, such as rash and pancytopenia, resembling certain rheumatological and hematological diseases. Chronic, excessive iodine consumption causes primary hypothyroidism. However, when iodine overconsumption becomes a regular part of daily dietary habits, it becomes difficult for patients to associate their symptoms with daily iodine consumption. Therefore, clinicians cannot obtain information on excessive iodine intake from the patient. Here, we present a case of hypothyroidism that was subsequently identified as caused by excessive dairy seaweed consumption for health purposes. This case report highlights the importance of a detailed dietary history in patients diagnosed with primary hypothyroidism without thyroid autoantibodies.

Real-world analysis of apalutamide-associated skin rash in Chinese patients with prostate cancer.

PURPOSE: This study aimed to explore the clinical characteristics of apalutamide-associated skin rash and management of skin rash in real-world Chinese patients with prostate cancer. METHODS: We investigated 138 patients with prostate cancer who received apalutamide in the Second Hospital of Tianjin Medical University from January 2022 to March 2023. The primary end points were the incidence of skin rash and the time to skin rash. The second end points were the grade of skin rash, the time to remission, the rate of recurrence of skin rash, clinical risk factors and management of skin rash. RESULTS: One hundred patients were analyzed. Patients were a median of 73 years old (IQR 68-77.75). Thirty-two patients (32%) developed apalutamide­associated skin rash. The median time to incidence and remission of skin rash were 57.5 and 11.5 days, respectively. Of 32 skin rash, 27 patients had apalutamide therapy maintained after rash remission. There were seven patients having recurrence of skin rash. By multivariable logistic regression analysis, we revealed that hypertension history (OR 3.22, 95% CI 1.09-9.53, p = 0.035), bad life-styles (OR 3.29, 95% CI 1.11-9.8, p = 0.032), ECOG ≥ 1 (OR 3.92, 95% CI 1.33-11.55, p = 0.013), and high tumor burden (OR 3.13, 95% CI 1.07-9.14, p = 0.037) were independently associated with higher incidence of skin rash. CONCLUSION: Nearly one-third of Chinese patients experienced skin rash after taking apalutamide in our study. The poor health patients might have a higher incidence of apalutamide-associated skin rash.

Time-Course Changes in Lamotrigine Concentration after Addition of Valproate and the Safety and Long-Term Tolerability of Lamotrigine-Valproate Combination Therapy.

The aim of this study was to evaluate the time-course changes in lamotrigine (LTG) concentration after addition of valproate (VPA) and the safety and tolerability of the combination therapy. We reviewed our therapeutic drug monitoring (TDM) database and found 345 patients on LTG who received add-on therapy with VPA. VPA had been added at least 12 weeks after patients finished stepwise LTG titration. Also, we retrospectively evaluated the LTG concentration after addition of VPA and the safety and long-term tolerability of LTG-VPA combination therapy. Plasma LTG concentration increased more than 1.5-fold within 15 d of addition of VPA and reached a peak at 30 d. The rate of increase in LTG concentration occurred in a VPA concentration-dependent manner. During the first 120 d after addition of VPA, adverse events were reported by 58 patients (16.8%), but no patient developed cutaneous reactions. Kaplan-Meier analysis showed estimated retention rates for LTG-VPA combination therapy of 74.5% at 5 years. At 5 years, the mean concentration of LTG was 11.1 µg/mL (43.3 µmol/L). Because addition of VPA leads to a marked increase in LTG concentration over a short period, TDM for LTG should be performed at the earliest from 14 d after starting VPA. At 120 d after starting VPA therapy, the higher LTG concentration due to addition of VPA is not associated with an increased risk of cutaneous reactions. Although LTG-VPA combination therapy increases LTG concentration, it is well tolerated and has a high long-term retention rate.

Real-world prostate-specific antigen response and progression to castration-resistant prostate cancer among men with metastatic castration-sensitive prostate cancer treated with apalutamide: a multi-institutional study in the Chu-shikoku Japan Urological Consortium.

BACKGROUND: Japanese men receiving apalutamide often experience skin-adverse events (AEs), possibly requiring treatment interruption or dose reduction. However, concerns have arisen regarding the impact of these adjustments on the efficacy of apalutamide. Our study evaluated the efficacy, safety, and persistence of apalutamide in men with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: We retrospectively reviewed the medical records of 108 men with mCSPC from 14 Japanese institutions. The primary outcomes were the efficacy of apalutamide: prostate-specific antigen (PSA) response (50%, 90% and < 0.2 decline) and progression to castration-resistant prostate cancer (CRPC). The secondary outcomes were the skin-AE and compliance of apalutamide. RESULTS: PSA50%, PSA90% and PSA < 0.2 declines were observed in 89.8, 84.3 and 65.7%, and the median time to CRPC progression was not reached. PSA < 0.2 decline and an initial full dose of apalutamide were significantly associated with a longer time to CRPC. The most common AE was skin-AE (50.9%), and there was no association between the occurrence of skin-AE and the time to CRPC (P = 0.72). The median apalutamide persistence was 29 months, which was longer in the initial full dose recipients than in the reduced dose recipients. The dosage is reduced in about 60% of patients within the first year of treatment in the initial full dose recipients. CONCLUSIONS: Our findings indicate the effectiveness of apalutamide in Japanese men with mCSPC, despite a substantial portion requiring dose reduction within a year among the initial full dose recipients.

Acute Respiratory Distress Syndrome due to Monkeypox Virus.

We report the first case of monkeypox virus (MPXV) associated acute respiratory distress syndrome (ARDS). A 34-year-old French woman with no medical history was admitted to the intensive care unit (ICU) for fever, altered mental status, hypotension and hypoxaemia. She presented with a diffuse skin rash with vesiculopustular lesions involving the four limbs and perineal ulcers with a skin swab positive for MPXV. On day 2, the patient presented moderate ARDS requiring invasive mechanical ventilation. She also had pleural empyema due to Streptococcus pyogenes. MPXV PCR was positive in the bronchoalveolar lavage, the pleural effusion and the blood. The patient was treated with tecovirimat. Despite the treatment, she had persistent viraemia for at least ten days. The patient condition rapidly improved; she was weaned from mechanical ventilation on day 18 despite the persistence of radiological lung opacities. She fully recovered and was discharged home on day 38 after admission. LEARNING POINTS: This is the first case of monkeypox virus associated ARDS in a young woman with no medical historyBiological follow-up showed disseminated MPXV and persistent viraemiaTecovirimat was well tolerated.

An eight-year old girl with fever and rash: What is the possible diagnosis?

In this clinical challenge, we describe the case of a previously healthy 8-year-old girl who presented to a primary care clinic with fever, reduced oral intake and malaise on day 3 of her illness. Clinical examination revealed that she was tachypnoeic and tachycardic. An erythematous rash was found across the bridge of her nose and cheeks, and several painless ulcers were noted in the oral cavity. Blood investigation showed thrombocytopenia, while urinalysis revealed microscopic haematuria and proteinuria. Useful initial diagnostic imaging studies were discussed, including bedside ultrasound in the ambulatory care setting. It is imperative that primary care providers be vigilant when encountering cases like this.

Clinical Profile, Risk Factors and Complications of Paediatric Herpes Zoster Ophthalmicus-A Case Series.

To study the clinical profile, risk factors and complications of paediatric Herpes zoster ophthalmicus (HZO). Case records of clinically diagnosed paediatric HZO over the past five years period were collected. An analysis was done with the existing data to determine the patient's clinical presentation, risk factors and treatment outcomes. Among seven children (three males and four females), two were less than ten years. Risk factors like previous history of chickenpox were present in one patient and immunosuppression in another. Child with immunosuppression also had h/o viral encephalitis three days before the onset of HZO. While two patients presented with disciform keratitis and three with anterior uveitis, the remaining did not have anterior segment involvement. Six out of seven patients retained 6/6 visual acuity at one month follow-up. Paediatric HZO is prevalent even in immunocompetent children without any identifiable risk factor. It generally has a good prognosis with minimum residual complications.