tbuckley/cabot-search huggingface dataset:
The limits of fair medical imaging AI in real-world generalization
Authors: Yuzhe Yang, Haoran Zhang, Judy W. Gichoya, Dina Katabi, Marzyeh Ghassemi
Journal: Nature Medicine (2024)

As artificial intelligence (AI) rapidly approaches human-level performance in medical imaging, it is crucial that it does not exacerbate or propagate healthcare disparities. Previous research established AI's capacity to infer demographic data from chest X-rays, leading to a key concern: do models using demographic shortcuts have unfair predictions across subpopulations? In this study, we conducted a thorough investigation into the extent to which medical AI uses demographic encodings, focusing on potential fairness discrepancies within both in-distribution training sets and external test sets. Our analysis covers three key medical imaging disciplines-radiology, dermatology and ophthalmology-and incorporates data from six global chest X-ray datasets. We confirm that medical imaging AI leverages demographic shortcuts in disease classification. Although correcting shortcuts algorithmically effectively addresses fairness gaps to create 'locally optimal' models within the original data distribution, this optimality is not true in new test settings. Surprisingly, we found that models with less encoding of demographic attributes are often most 'globally optimal', exhibiting better fairness during model evaluation in new test environments. Our work establishes best practices for medical imaging models that maintain their performance and fairness in deployments beyond their initial training contexts, underscoring critical considerations for AI clinical deployments across populations and sites.
AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient
Authors: James J. Dowling, Terry Pirovolakis, Keshini Devakandan, Ana Stosic, Mia Pidsadny, Elisa Nigro, Mustafa Sahin, Darius Ebrahimi-Fakhari, Souad Messahel, Ganapathy Varadarajan, Benjamin M. Greenberg, Xin Chen, Berge A. Minassian, Ronald Cohn, Carsten G. Bonnemann, Steven J. Gray
Journal: Nature Medicine (2024)

Abstract There are more than 10,000 individual rare diseases and most are without therapy. Personalized genetic therapy represents one promising approach for their treatment. We present a road map for individualized treatment of an ultra-rare disease by establishing a gene replacement therapy developed for a single patient with hereditary spastic paraplegia type 50 (SPG50). Through a multicenter collaboration, an adeno-associated virus-based gene therapy product carrying the AP4M1 gene was created and successfully administered intrathecally to a 4-year-old patient within 3 years of diagnosis as part of a single-patient phase 1 trial. Primary endpoints were safety and tolerability, and secondary endpoints evaluated efficacy. At 12 months after dosing, the therapy was well tolerated. No serious adverse events were observed, with minor events, including transient neutropenia and Clostridioides difficile gastroenteritis, experienced but resolved. Preliminary efficacy measures suggest a stabilization of the disease course. Longer follow-up is needed to confirm the safety and provide additional insights on the efficacy of the therapy. Overall, this report supports the safety of gene therapy for SPG50 and provides insights into precision therapy development for rare diseases. Clinical trial registration: NCT06069687 .
Reciprocal regulation of T follicular helper cells and dendritic cells drives colitis development
Authors: Xue Bai, Sijie Chen, Xinxin Chi, Bowen Xie, Xinyi Guo, Han Feng, Peng Wei, Di Zhang, Shan Xie, Tian Xie, Yongzhen Chen, Mengting Gou, Qin Qiao, Xinwei Liu, Wei Jin, Wei Xu, Zixuan Zhao, Qi Xing, Xiaohu Wang, Xuegong Zhang, Chen Dong
Journal: Nature Immunology (2024)
PA13 A hair’s breadth from misdiagnosis
Authors: Nicola Kearney, Nicholas Stefanovic, Gregg Murray, Kevin Molloy, Richard Watchorn
Journal: British Journal of Dermatology (2024)

Abstract A 15 year-old boy presented with a 2-year history of patches of hair loss on his body, and skin changes. Initial examination revealed scattered erythematous patches with associated follicular accentuation and concurrent nonscarring alopecia, predominantly affecting his limbs. His background included acne, gynaecomastia and exercise-induced asthma. His only regular medication was a salbutamol inhaler. Punch biopsies from the left shin and right arm demonstrated mild acanthosis of the epidermis with slight hyperkeratosis, focal parakeratosis and minimal spongiosis with occasional lymphocyte exocytosis. The initial biopsies were reported as nonspecific changes of lymphocytic folliculitis with spongiosis. Following clinicopathological review a diagnosis of alopecia mucinosa was considered. Further histopathological review confirmed spongiosis in the superficial to midpart of the hair follicle. Additionally noted was exocytosis of lymphocytes, which displayed subtle cytological atypia marked by nuclear irregularity and slight enlargement, and immunohistochemistry indicated a predominance of CD4+ T cells, raising the possibility of mycosis fungoides. Subsequent incisional biopsies were performed for T-cell clonality studies using the BIOMED-2 protocol and were polyclonal. Expert external histopathologist opinion was sought and this supported a diagnosis of folliculotropic mycosis fungoides (FMF), a condition rarely described in paediatric patients. The patient had patch-stage disease of his arms and legs with follicular accentuation and his modified Severity-Weighted Assessment Tool (mSWAT) score was 3.9. He had no lymphadenopathy or B symptoms. He was initiated on mometasone furoate 0.1% and his current management plan is for observation for clinical response and for further investigations, including lymphocyte subsets and high-throughput sequencing of the T-cell receptor, which are awaited. Although T-cell gene receptor rearrangement studies indicated polyclonality, their sensitivity is estimated at 50–70%. Based on the clinical and histological features the patient was diagnosed with stage IA FMF. FMF is characterized histologically by atypical CD4+ T lymphocytes that surround and infiltrate the hair follicles (folliculotropism) and should be considered in lesions resembling keratosis pilaris but in an unusual distribution and/or in clusters. Epidermotropism is typically absent in FMF, and concomitant follicular mucinosis is frequently observed. Paediatric follicular MF is rare, but this case highlights that in cases of suspected alopecia mucinosa, even in paediatric patients, a diagnosis of FMF merits careful consideration (Reiter O, Amitay-Laish I, Oren-Shabtai M et al. Paediatric mycosis fungoides – characteristics, management and outcomes with particular focus on the folliculotropic variant. J Eur Acad Dermatol Venereol 2022; 36: 671–9).
PA23 Glomuvenous malformation or blue rubber bleb naevus syndrome: a case highlighting how a genetic diagnosis can avoid invasive testing and the need for long-term follow-up
Authors: Rebecca Lapsley, Sharmela Darné, Paul Brennan, Andrew Carmichael
Journal: British Journal of Dermatology (2024)

Abstract Glomuvenous malformation is an inherited autosomal dominant venous malformation that presents with multifocal cutaneous blue purple vascular lesions. An important differential that should be excluded is blue rubber bleb naevus (BRBN) syndrome, which presents with similar cutaneous lesions. However, the critical difference is that the latter is associated with visceral lesions including in the gastrointestinal tract. This can cause intussusception or haemorrhage with significant sequelae including severe anaemia, consumptive coagulopathy and sometimes death. These patients require gastrointestinal investigations and close long-term follow-up. We describe the case of a 16-year-old girl who presented to clinic with multiple small venous malformations affecting her eyelid, arms, knee and back. Most lesions were present from birth; however, some were acquired in childhood and had increased in size. Some were tender but there was no reported bleeding. She had no significant past medical history. Her mother and maternal grandmother had similar lesions. Full blood count and coagulation studies were normal. Genomic DNA from blood samples was sent for a venous malformation panel, which demonstrated a glomulin (GLMN) c.157_161del mutation. This confirmed the diagnosis of familial glomuvenous malformation rather than BRBN syndrome. BRBN syndrome and glomuvenous malformation present as clinically similar entities with primary purple–blue papules, which are often multifocal and widespread. Lesions are often congenital but can increase in number and size particularly during puberty. Both conditions are inherited in an autosomal dominant manner (Lu R, Krathen R, Sanchez R et al. Multiple glomangiomas: potential for confusion with blue rubber bleb nevus syndrome. J Am Acad Dermatol 2005; 52: 731–2). Histopathology can be useful to distinguish between the two conditions; however, this requires a biopsy. Loss-of-function mutations in the GLMN gene cause glomuvenous malformations. These were first reported by Brouillard et al. in 2002, and c.157­_161del is the most frequent mutation (Brouillard P, Boon LM, Revencu N et al. Genotypes and phenotypes of 162 families with a glomulin mutation. Mol Syndromol 2013; 4: 157–64). With this case we wish to highlight how useful genetic testing is diagnostically for patients presenting with these cutaneous lesions. The discovery of the GLMN gene has allowed clinicians to distinguish glomuvenous malformations from other more concerning venous anomalies such as BRBN syndrome and thus avoid an invasive biopsy. Patients can be reassured and avoid the need for long-term follow-up, regular blood tests or gastrointestinal investigations.
British Society for Paediatric and Adolescent DermatologyOral presentationsPA01 (P094) Oral tofacitinib monotherapy for the management of moderate-to-severe alopecia areata in children and adolescents: a retrospective analysis of 36 cases
Authors: Hitaishi Mehta, Rahul Mahajan, Dipankar De, Sanjeev Handa
Journal: British Journal of Dermatology (2024)

Abstract Alopecia areata (AA) poses a significant challenge in the paediatric population, with limited treatment options. Oral tofacitinib has emerged as a promising modality, with case reports and small series suggesting safe and effective use in children with AA. This retrospective analysis sought to expand the knowledge base around tofacitinib’s role in managing AA in the younger population and to provide valuable insights into challenges encountered when faced with no response to treatment. This retrospective chart review spanned from January 2021 to December 2023 and included 36 patients aged ≤ 16 years with moderate-to-severe AA [Severity of Alopecia Tool (SALT) score &amp;gt; 25], who received ≥ 6 months of oral tofacitinib therapy. The treatment response was defined as ≥ 75% reduction in SALT score (SALT 75) at 6 months. Other outcome measures of interest included times to attain SALT 50, SALT 75, SALT 90 and SALT100, and incidence of adverse events. In total 36 patients were included, with a mean age of 10.1 years (SD 3.8, range 3–16), with 17 male and 19 female patients. AA subtypes included patchy (19%), ophiasis (17%), subtotalis (28%), totalis (8%) and universalis (28%). The mean SALT score at baseline was 73.1 (SD 26.7). The mean duration of oral tofacitinib treatment was 8.69 months (SD 3.17, range 6–16). SALT 50 was achieved by 26 patients, with an equivalent number attaining SALT 75. Additionally, 24 patients reached SALT 90, while 19 patients reached SALT 100. The mean (SD, range) durations in months to achieve SALT 50, SALT 75, SALT 90 and SALT 100 were 2.81 (1.16, 1–6), 4.08 (1.69, 1–8), 5.71 (2.14, 3–10) and 6.74 (2.35, 3–12), respectively. Ten of the 36 patients (28%) were classified as nonresponders. Nonresponders exhibited a higher median total duration of illness, higher baseline SALT score, and higher incidence of atopy and nail involvement compared with responders. Adverse events were noted in nine patients, with two cases necessitating treatment discontinuation due to adverse events. Among those not showing a response, three patients each underwent a transition to combination therapy of oral steroids with methotrexate and topical immunotherapy with diphenylcyclopropenone. Notably, regrowth was observed in two patients from the former group, while none from the latter group experienced similar positive outcomes after the therapeutic strategy shift. Limitations of the study include the retrospective nature and small sample size. This comprehensive analysis enriches the existing literature on the role of tofacitinib in paediatric AA, addressing gaps in approved treatments and providing valuable guidance for clinicians navigating the challenges of nonresponsiveness in this vulnerable population.
PA14 An interesting case of congenital syphilis
Authors: Elisabetta Muttoni, Paula Beattie
Journal: British Journal of Dermatology (2024)

Abstract Congenital syphilis occurs due to transplacental transmission of Treponema pallidum from mother to fetus during pregnancy or rarely during childbirth. Intrauterine infection can result in a variety of presentations ranging from asymptomatic infection to cutaneous and visceral changes and even stillbirth and perinatal death. We present the case of a 15-week-old infant with congenital syphilis presenting with a persistent rash, organomegaly, haematological abnormalities and epistaxis. The patient was a 15-week-old male infant seen by the general paediatricians at the age of 6 weeks with a widespread nonspecific exanthematous rash, which was initially felt to be a viral exanthem due to a preceding episode of bronchiolitis. However, the rash persisted, and after developing bilateral epistaxis he attended hospital and was found to have hepatosplenomegaly, confirmed on ultrasound scan, and a markedly raised white cell and lymphocyte count along with low haemoglobin and platelet count. While he was under the haematology team, dermatology were asked to review the patient. He was noted to have small brownish–pink plaques over the fingers and knuckles and scattered throughout the body, bluish macules on the legs, and peeling on the soles. He was also noted to have a flattened nose and sounded congested. A diagnosis of congenital syphilis was suggested and he was referred on to the infectious disease team. Investigations showed he was positive for T. pallidum polymerase chain reaction on rectal and mouth swabs and urine sample, but not in cerebrospinal fluid. He has completed a 10-day course of intravenous benzylpenicillin. In the postnatal period, congenital syphilis can present with haematological, visceral and cutaneous manifestations. The most common early signs, which present at birth or appear in the first 2 years of life, include hepato­splenomegaly, rash, fever, rhinitis (snuffles) and generalized lymphadenopathy. Leucocytosis and thrombocytopenia are also recognized (Woods CR. Congenital syphilis – persisting pestilence. Pediatr Infect Dis J 2009; 28: 536–7). Penicillin is the gold-standard treatment for syphilis as resistance of T. pallidum to penicillin has never been reported (Peeling RW, Mabey D, Kamb ML et al. Syphilis. Nat Rev Dis Primers 2017; 3: 17073). Patients who are allergic to penicillin should be treated with doxycycline or ceftriaxone. It is important to consider congenital syphilis as a potential differential in any infant who presents with a rash, organomegaly and haematological abnormalities such as the case we present, and we hope to increase awareness to facilitate early diagnosis and prompt treatment.
PA17 Multiple lesions in a child mimicking juvenile xanthogranulomas
Authors: Siwaporn Hiranput, Essam Raweily, Dalia Saidely Alsaadi
Journal: British Journal of Dermatology (2024)

Abstract An 11-year-old White girl presented with a lesion on her left arm, present since she was a toddler. The lesion had increased in size over the past year with associated discomfort. Two further lesions appeared over a 12-month period. She was born at full term, and had no developmental delay and no past medical history. On examination, a 15 × 20-mm firm yellow–orange plaque was noted on her left upper arm without epidermal changes, and two smaller lesions with similar appearance were present on her right upper arm and right posterior thigh. There was no palpable lymphadenopathy or hepatosplenomegaly. She did not have dysmorphic facial features or short stature. The clinical impression was that of juvenile xanthogranulomas. As the arm lesion was symptomatic, it was excised with a narrow margin. Excisional biopsy showed cells with abundant eosinophilic granular cytoplasm, bland chromatin and nuclei. There was no lymphovascular or perineural invasion, mitotic figures, necrosis or apoptotic cells. Features were consistent with granular cell tumour (GCT). Subsequently, a biopsy of the thigh lesion confirmed GCT. GCT is a rare soft-tissue tumour, thought to originate from Schwann cells. The expression of S100 proteins in GCT supports its neural cell origin. There is a predilection for women in their fourth to sixth decades. Half of cases are found on the head, neck and oral cavity; although any body site can be affected, including internal organs. GCTs are usually solitary, but multiple lesions have been described in up to 25% of cases. Multiple GCTs in paediatric populations have been reported to be associated with genetic syndromes including Leopard syndrome, Noonan syndrome and neurofibromatosis type 1. Most cases of GCTs are benign; however, 1–2% can be malignant. The latter may be suspected when specific clinical and histological features are present. High-risk clinical features include lesions more than 4 cm in size, rapid growth, ulceration, necrosis and lymph node involvement. High-risk histological features are high mitotic activity, necrosis, high nuclear-to-cytoplasmic ratio, spindle cells, vesicular or large nuclei, and pleomorphism. The recommended treatment for benign and malignant GCTs is complete surgical excision to prevent recurrence. Our patient was reviewed by genetics, who felt that further genetic testing was not indicated given her normal physical examination. There was no sign of disease recurrence at 1 year. She remained under our regular follow-up. In conclusion, we report an unusual case of multiple cutaneous GCTs arising in the extremities in a paediatric patient. Although the presentation is rare, our case highlights that GCTs should be considered in the differential diagnosis of cutaneous tumours in the paediatric population.
PA24 Concomitant Crohn disease and scurvy: an unusual presentation revealing nutritional challenges
Authors: Matheus Alves Pacheco, Rubiana Sarto, Fernanda Ramos Paes Lima, Christine Aparecida Wegner, Ariel Cordova Rosa, Gabriella Di Giunta Funchal, Athos Martini
Journal: British Journal of Dermatology (2024)

Abstract This case report presents a 15-year-old boy newly diagnosed with Crohn disease (CD), currently under treatment with prednisone and azathioprine. The patient was admitted to the hospital due to diffuse abdominal pain, diarrhoea and fever. Remarkably, after 5 days of hospitalization, he developed purpuric lesions on his wrists, abdomen and lower limbs. Dermoscopic examination of the cutaneous petechiae revealed an intriguing finding: whitish hair follicles exhibiting a distinctive ‘corkscrew’ hair pattern surrounded by a haemorrhagic violaceous halo. This dermoscopic profile strongly suggested the presence of scurvy. Histological analysis provided further insight, demonstrating perifollicular haemorrhage and interstitial extravasation of red blood cells. While nutritional deficiencies are commonly linked to CD, vitamin C deficiency is less frequently identified and reported, despite its prevalence. The challenge lies in the potential overlap of symptoms between active CD and scurvy, making the diagnosis of vitamin C deficiency more elusive in patients with CD. This case underscores the importance of considering vitamin C deficiency in the differential diagnosis of cutaneous manifestations in individuals with CD. Clinicians should be vigilant in identifying such nutritional deficiencies to ensure timely intervention and prevent complications associated with scurvy.
DS13 Pregnancy-associated melanoma: a UK-wide service evaluation
Authors: Kate Lawlor, Sofia Hadjieconomou, Ruwani Katugampola, Caroline Mills, Vincent Li, Suchitra Rajan
Journal: British Journal of Dermatology (2024)

Abstract There are currently no guidelines in the UK regarding management of pregnancy-associated melanoma (PAM). It is estimated that one-third of women diagnosed with melanoma are of childbearing age and numbers are rising (Still R, Brennecke S. Melanoma in pregnancy. Obstet Med 2017; 10: 107–12). Melanoma can metastasize to the placenta. Therefore, a diagnosis of PAM complicates decisions regarding staging and treatment (Carter TJ, George C, Harwood C, Nathan P. Melanoma in pregnancy: diagnosis and management in early-stage and advanced disease. Eur J Cancer 2022; 166: 240–53). A UK-wide survey distributed to members of the British Society for Dermatological Surgery (BSDS) has shown 23 cases of PAM and we await data of up to 26 additional identified cases. The data collected on these cases demonstrate an average age of 33.2 years at the time of diagnosis, with a range from 22 to 46 years. The stage of pregnancy at the time of diagnosis ranged from 2/40 gestation to 11 months postpartum. The diagnosis was primary melanoma in 18 patients, with metastatic disease in five patients. Breslow thickness ranged from in situ melanoma to &amp;gt; 4 mm. Fifteen patients underwent narrow and subsequent wide local excision during pregnancy. Two patients delayed their wide local excision until after pregnancy. Two patients underwent sentinel lymph node biopsy during pregnancy, one of whom also underwent an axillary lymph node dissection during pregnancy. Three patients had immunotherapy for stage 4 disease postpartum. One of these patients delivered at term, having being diagnosed with metastatic melanoma at 32 weeks. She is currently having palliative treatment for advancing metastatic disease. Another of these patients underwent an elective caesarean section at 35 weeks’ gestation in order to commence immunotherapy and is likely to need further adjuvant treatment after a relapse. The details of the obstetric outcome for the third patient are awaited, but it is known that the patient has died from complications of metastatic melanoma. The placenta was sent for histological examination for only one of the patients and it did not show any evidence of metastases. The baby had a full-skin examination after birth in four cases (in three patients on one occasion only), with none showing any abnormalities secondary to melanoma. Four of the patients have successfully completed follow-up. Fifteen patients are currently undergoing follow-up, including one who is having palliative treatment and one who is due to recommence on immunotherapy. Four patients have died from complications of melanoma. We await data on up to 26 additional cases of PAM to include in this study.