Mycophenolate mofetil treatment of an H syndrome patient with a
            <scp>
              <i>SLC29A3</i>
            </scp>
            mutation

Behrangi, Elham; Sadeghzadeh‐Bazargan, Afsaneh; Khosravi, Sepehr; Shemshadi, Mahsa; Youssefian, Leila; Vahidnezhad, Hassan; Goodarzi, Azadeh; Uitto, Jouni

doi:10.1111/dth.14375

Cited by 12 publications

(3 citation statements)

References 13 publications

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“…For instance, several immune suppressive medications (anti-tumor necrosis factor, anti-interleukin 1, cyclosporine, azathioprine) have been tried with limited to no success [14,15]. The anti-sclerotic immune-suppressive medications mycophenolate mofetil [16], methotrexate [14], and tocilizumab (anti IL-6) [14], on the other hand, showed promising results in the treatment of sclerotic skin changes, arthritis, and short stature, respectively. In parallel with the previous results, we had tried methotrexate therapy for several months; however, it gave only a minimal response regarding the joint pain but did not improve the sclerotic skin changes.…”

Section: Discussionmentioning

confidence: 99%

Clinical Progression and Manifestations of H Syndrome: A Case Report of Failed Treatment Option

Al-Haddab,

Al Muqarrab,

Alhumidi

et al. 2024

Am J Case Rep

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Congenital defects/diseases Background:H syndrome is an autosomal recessive disorder of histiocytic proliferation with clinical spectrum of unique cutaneous and systemic manifestations. There is no consistent treatment for the disease, and all available options are based on case reports. Here, we present the chronological progression of a case of H syndrome with typical cutaneous manifestations that was misdiagnosed early as meningitis-induced sensorineural hearing loss and later as a non-defined autoimmune connective tissue disease. A new tried, although failed, treatment option is described as well. Case Report:A 31-year-old Saudi woman born of a consanguineous marriage presented to our dermatology clinic with symmetrical indurated hyperpigmented to violaceous plaques over the medial thighs, upper legs, lower back, volar wrists, and upper arms, associated with hypertrichosis. Hallux valgus of the big toes was clinically detected as well. She had a history of sensorineural deafness, diabetes mellitus, chronic anemia, and hypothyroidism. Genetic analysis of the patient showed a homozygous frameshift pathogenic variant of the SLC29A3 gene, c.243del p.(Lys81Asnfs*20). Systemic treatments in the form of methotrexate and imatinib had been tried; however, both failed to control her sclerotic cutaneous changes. Conclusions:Knowing the early life presentation and the variable clinical symptoms of H syndrome is crucial in early intervention and further prevention of the non-reversible changes. Moreover, avoiding unnecessary immunosuppressive medication use is warranted in certain circumstances.

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Section: Discussionmentioning

confidence: 99%

Clinical Progression and Manifestations of H Syndrome: A Case Report of Failed Treatment Option

Al-Haddab,

Al Muqarrab,

Alhumidi

et al. 2024

Am J Case Rep

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“…Generally, Ciclosporine receded the symptoms, but arthritis and persistent inflammation did not improve with the mentioned treatment ( 9 ). The positive effect on mycophenolate mofetil is also described on hyperpigmentation and joint stiffness with promising results ( 24 ). What seems to be the advantage of Tocilizumab is the fact that this medication has higher success in the treatment of inflammatory manifestations such as arthritis and organ infiltration ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

H syndrome treated with Tocilizumab: two case reports and literature review

et al. 2023

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H syndrome is a rare autosomal recessive genetic disorder characterized by the following clinical features: cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, short stature, hallux valgus, hyperglycemia, fixed flexion contractures of the toe joints, and the proximal interphalangeal joints. In rare cases, autoinflammatory and lymphoproliferative manifestations have also been reported. This disorder is due to loss-of-function mutations in SLC29A3 gene, which encode the equilibrative nucleoside transporter ENT3. This deficiency leads to abnormal function and proliferation of histiocytes. H syndrome is part of the R-group of histiocytosis. We report two different cases, one was diagnosed in adulthood and the other in childhood. The first case reported is a 37-year-old woman suffering from H syndrome with an autoinflammatory systemic disease that begins in adulthood (fever and diffuse organ’s infiltration) and with cutaneous, articular, auditory, and endocrinological manifestations since childhood. The second case reported is a 2-year-old girl with autoinflammatory, endocrine, and cutaneous symptoms (fever, lymphadenopathy, organomegaly, growth delay, and cutaneous hyperpigmentation). Homozygous mutations in SLC29A3 confirmed the diagnosis of H syndrome in both cases. Each patient was treated with Tocilizumab with a significant improvement for lymphoproliferative, autoinflammatory, and cutaneous manifestations. Both cases were reported to show the multiple characteristics of this rare syndrome, which can be diagnosed either in childhood or in adulthood. In addition, an overview of the literature suggested Tocilizumab efficiency.

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“…According to recent reports, mycophenolate mofetil or tocilizumab medication may affect the course of the illness, leading to improvements in scleroderma-like skin lesions, arthritis, sensorineural deafness, and growth. The fact that these symptoms are affected by immunomodulatory medications is in line with their immune pathogenesis [5][6][7]. Anti-inflammatory medications, however, are frequently initiated many years after the onset of symptoms due to poor awareness of their rheumatological pertinence, making it challenging to assess their true efficacy in preventing illness-related organ damage.…”

Section: Introductionmentioning

confidence: 99%

Rheumatological complaints in H syndrome: from inflammatory profiling to target treatment in a case study

Tesser,

Valencic,

Boz

et al. 2024

Pediatr Rheumatol

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Background H Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene. It is characterized by a wide range of clinical manifestations, many of which are related to the immune-rheumatological field. These include scleroderma-like skin changes, deforming arthritis, and enlarged lymph nodes. The condition also features cardiac and endocrine defects, as well as hearing loss, for which the immune pathogenesis appears less clear. Immunomodulatory medications have been shown to improve many symptoms in recent experiences. Case presentation A 21-year-old girl was referred to our institute after being diagnosed with H syndrome. Her medical history was characterized by the development of finger and toe deformities, which developed since the first years of life and progressively worsened with clinodactyly. At 6 years of age, she was diagnosed with diabetes mellitus without typical autoantibodies and with bilateral sensorineural hearing loss. She also complained of frequent episodes of lymphadenopathy, sometimes with colliquation and growth retardation due to pancreatic insufficiency. It wasn’t until the genetic diagnosis of H syndrome that the continual increase in acute phase reactants was noticed, suggesting that an immunological pathogenesis may be the source of her problems. During her visit to our institute, she reported serious pain in both feet and hands and difficulty walking due to knee arthritis and muscle contractures. Conventional therapy with steroid injection in affected joints and methotrexate only led to partial improvement. After a thorough assessment of her inflammatory profile showing a high interferon score, the girl received treatment with baricitinib. Furthermore, based on recent data showing that SLC29A3 deficiency results in interferon production because of Toll-like Receptor 7 activation in lysosomes, hydroxychloroquine was also added. The combination of the two drugs resulted for the first time in a rapid and persistent normalization of inflammatory markers, paralleled by a dramatic improvement in symptoms. Conclusions We describe the results of inhibiting IFN inflammation in H syndrome and discuss how JAK inhibitors and antimalarials might represent a mechanistically based treatment for this orphan drug disorder.

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Mycophenolate mofetil treatment of an H syndrome patient with a SLC29A3 mutation

Abstract: H syndrome is a complex multi-organ disorder with autosomal recessive inheritance. The skin manifestations include early onset hyperpigmentation and hypertrichosis, followed by skin induration often diagnosed as scleromyxedema and morphea. There

Cited by 12 publications

References 13 publications

Clinical Progression and Manifestations of H Syndrome: A Case Report of Failed Treatment Option

Clinical Progression and Manifestations of H Syndrome: A Case Report of Failed Treatment Option

H syndrome treated with Tocilizumab: two case reports and literature review

Rheumatological complaints in H syndrome: from inflammatory profiling to target treatment in a case study

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