Clinical and genetic characteristics of PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome

Objective To summarise the clinical and genetic characteristics of three children with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome. Methods This study retrospectively analysed the clinical and genetic data of three children with PAMI syndrome in our hospital between April 2018 and January 2020. Results One male and two female children were 6 years and 5 months, 8 years and 7 months, and 13 years and 3 months of age. All three patients had a recurrent blood trilineage hypoplasia and splenomegaly. Patient 1 had pyoderma gangrenosum, and Ludwig’s angina. Patient 2 had pyogenic arthritis, and pyoderma gangrenosum. Patient 3 had hepatomegaly, pyogenic arthritis, and pulmonary hypertension. Laboratory tests revealed that all three children had elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Patient 1: C-antineutrophilic cytoplasmic antibodies(c-ANCA), positive; antiglobulin test (Coombs), positive. Patient 2: blood zinc, 4.38 mg/L (elevated). Patient 3: Antinuclear antibodies (ANA), 1:100, β2 glycoprotein I, positive; Coombs test, positive; RF, 28.3 U/ml (elevated); C3, 0.77 g/L (decreased). Genetic testing showed that all 3 patients had PSTPIP1 c.748G > A (p.E250K) spontaneous heterozygous mutations, suggesting the diagnosis of PAMI syndrome. Patient 1 was treated with a combination of methylprednisolone and cyclosporine for 8 months. The patient did not develop new skin lesions. The blood count showed mild neutropenia. The spleen was considerably retracted and the CRP became normal. Patient 2 was treated with etanercept and methylprednisolone. The patient had no further arthralgias and pyoderma gangrenosum showed improvement. The spleen was smaller than before. White blood cells were shown to be approximately 2–3 × 109/L. The haematocrit, platelets, CRP, and AESR were normal. Patient 3 was treated with methylprednisolone, methotrexate, and infliximab 4 times. The patient’s joint symptoms disappeared gradually and the liver retracted markedly. The pulmonary artery pressure returned to normal. Moreover, Coombs test result was negative. CRP and AESR were lower than before. Conclusion PAMI syndrome can manifest as pyogenic arthritis, pyoderma gangrenosum, acne, and trilineage hypoplasia, as well as autoimmune diseases. Glucocorticoid and immunosuppressive therapy are partially effective and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing is helpful to confirm diagnosis.

A Case of Psuedohypoparathyroidism Unmasked by COVID-19 and Rhabdomyolysis

Background: Psuedohypoparathyroidism type 1 b (PHP 1b) is a rare condition characterized by hormone resistance with PTH. It is caused by imprinting defect of the GNAS gene and is acquired as autosomal dominant. Compared with Pseudohypoparathyroidism type 1a (PHP1a), PHP1b does not have the characteristic physical features know as Albright hereditary osteodystrophy or AHO. Results: 12-year-old female with unremarkable past medical history presented with seizures. She has been complaining of leg pain for a week but on the day of presentation noted to have stiffening and shortness of breath. There was no history of cough, fever, leg trauma, headache, dysuria, hematuria or dark urine. She had no significant family history. Work up revealed severe hypocalcemia of 4.6 mg/ dL and elevated phosphorus (7.1mg/dl). There was no hypoglycemia and other electrolytes including renal function were normal. Patient also had normal inflammatory markers, normal fibrinogen, and normal ferritin. Urine was positive for trace protein and was positive for myoglobin. Alkaline phosphatase was normal. Urine toxicology screen was negative. Hand X-rays did not showed the shortening of metacarpal bones and kidney ultrasound was normal. After IV calcium bolus, calcium barely increased at 5.0. Interestingly CK was noted to be elevated at 3,794 U/L. Patient physical exam was normal and there was no signs of Albright hereditary osteodystrophy (AHO). Patient was positive for COVID19. Patient required intensive fluid therapy to correct CK which increased up to 11,223 U/L on 3rd day of admission. It eventually came down back to normal on the 6th day. Creatinine levels remained normal. Patient continued to receive high dose calcium and calcitriol supplement and discharged with calcium of 8.5 mg/dL and phosphorus of 7.8 mg/dL. Additional work up showed PTH of 885 pg/mL consistent with pseudohypoparathyroidism. Vitamin D levels and thyroid function were normal. Genetic testing for pseudohypoparathyroidism is awaited. Conclusion: Psuedohypoparathyroidism type 1 b (PHP 1b) is a rare endocrine disorder presenting with hypocalcemia, hyperphosphatemia and increased PTH values due to a variable resistance to target organs. As in our case it was unmasked by COVID 19 infection and rhabdomyolysis. Best of our knowledge there is no such unusual case reported in children. Severe hypocalcemia likely due to combination of factors including tissue calcium deposition, hyperphosphatemia, and skeletal resistance to PTH. As published in some recent reports, this case also illustrates that rhabdomyolysis could be potential complication of SARS- CoV2 infection in early stage with normal renal function, which warrants further research.

THALAMIC TUBERCULOMA AND HEMICHOREA.

25 years old female diagnosed to be having retro viral infection for past six months developed subacute onset of involuntary movements of left upper and lower limb in the form of flowing movements from proximal to distal parts of the limb. On examination vitals were stable, routine blood investigations were normal. CXR and ECG were normal. Patient CD4 count is 179. Neuro-imaging revealed T2 and flair hyper intensity and T1 hypo intensity with out any evidence of diffusion restriction noted in right thalamus. Possibility of TUBERCULOMA in right side of thalamus.

Thigh-Muscle and Patient-Reported Function Early After Anterior Cruciate Ligament Reconstruction: Clinical Cutoffs Unique to Graft Type and Age

Context Patient-reported function is an important outcome in anterior cruciate ligament rehabilitation. Identifying which metrics of thigh-muscle function are indicators of normal patient-reported function can help guide treatment. Objective To identify which metrics of thigh-muscle function discriminate between patients who meet and patients who fail to meet age- and sex-matched normative values for patient-reported knee function in the first 9 months after anterior cruciate ligament reconstruction (ACLR) and establish cutoffs for these metrics by covariate subgroups. Design Cross-sectional retrospective study. Setting Laboratory. Patients or Other Participants A total of 256 patients (129 females, 128 males; age = 17.1 ± 3.0 years, height = 1.7 ± 0.1 m, mass = 74.1 ± 17.9 kg, months since surgery = 6.4 ± 1.4), 3 to 9 months after primary unilateral ACLR. Main Outcome Measure(s) We stratified the sample into dichotomous groups by the International Knee Documentation Committee (IKDC) score (IKDCMET, IKDCNOT MET) using sex- and age-matched normative values. We measured quadriceps and hamstrings isokinetic (60°/s) torque and power bilaterally. Normalized quadriceps and hamstrings peak torque (Nm/kg) and power (W/kg), limb symmetry indices (LSI, %), and hamstrings : quadriceps ratios were calculated. Logistic regression indicated which of these metrics could predict IKDC classification while controlling for age, graft type, and sex. Receiver operating characteristic curves established cutoffs for explanatory variables for both total cohort and covariate subgroups. Odds ratios (OR) determined the utility of each cutoff to discriminate IKDC status. Results Quadriceps torque LSI (≥69.4%, OR = 3.6), hamstrings torque (≥1.11 Nm/kg, OR = 2.1), and quadriceps power LSI (≥71.4%, OR = 2.0) discriminated between IKDC classification in the total cohort. Quadriceps torque LSI discriminated between IKDC classification in the patellar-tendon graft (≥61.6%, OR = 5.3), hamstrings-tendon graft (≥71.8%, OR = 10.5), and age <18 years (≥74.3%, OR = 5.2) subgroups. Hamstrings torque discriminated between IKDC classifications in the age <18 years (≥1.10 Nm/kg, OR = 2.6) subgroup. Conclusions Quadriceps torque LSI, hamstrings torque, and quadriceps power LSI were the most useful metrics for predicting normal patient-reported knee function early after ACLR. Further, cutoff values that best predicted normal patient-reported function differed by graft type and age.

Retroperitoneal abscess secondary to the perianal abscess: a surgical dilemma

Perianal abscess accounts for approximately two third of anorectal infection. Perianal abscess spreading retroperitoneally and forming extensive abscess is very rarely encountered. We are presenting a 33 year old newly diagnosed diabetic patient who presented initially with fever, pain in right loin region and burning micturition since 1 week. Patient also took care of pain during defecation. On DRE, boggy swelling was noted in right lateral wall. USG abdomen and pelvis was normal. Patient diagnosed to have perianal abscess and incision and drainage was done. Subsequently patient developed severe right loin pain and continuous high grade fever. CT abdomen pelvis was done which was suggestive of purulent content retroperitoneally extending to right loin for which incision and drainage was done. Antibiotics as per culture report administered and patient improved.