Barbara E. Ostrov

MRI evaluation of diabetic muscle infarction

Diabetic muscle infarction (DMI) is a painful and potentially serious complication in patients with poorly controlled diabetes mellitus. The incidence of DMI is likely much greater than reports in the literature suggest, perhaps secondary to the difficulty in making the diagnosis and excluding other more serious etiologies. This paper describes the role of MRI in the evaluation of a diabetic patient with a painful, swollen limb. Early application of MRI can more accurately classify the disease process and focus the differential diagnosis, thus avoiding the hazards of medical therapy associated with other etiologies such as deep venous thrombosis, cellulitis, or osteomyelitis. This paper describes the evaluation and diagnostic pitfalls encountered in two patients. MRI techniques and applications are presented with a discussion of clinical and radiological differential diagnoses.

Vasculitis associated with antiphospholipid syndrome

Several syndromes involving antiphospholipid antibodies have been described in the literature. Although the varied clinical manifestations have been well delineated, the vascular pathophysiology in patients with these antibodies remains unclear. Vascular damage is often described as a vasculopathy; however, several case reports have described an associated vasculitis. We report two patients with manifestations of antiphospholipid antibody syndrome (APLS) and concurrent vasculitis. The first patient, a 42-year-old man, presented with abdominal pain and fevers. The second patient, a 39-year-old man, presented with fever and testicular pain. Both were ultimately felt to have polyarteritis nodosa associated with APLS. Their complicated hospital courses and difficulties we encountered in diagnosing and treating them are discussed. The literature describing other cases of vasculitis associated with antiphospholipid antibody syndrome is reviewed. Whether the presence of antiphospholipid antibodies favors the development of vasculitis or vice versa is not clear. Further studies are needed to address this question and to determine optimal therapeutic regimens in these critically ill patients.

Differentiation of systemic juvenile rheumatoid arthritis from acute leukemia near the onset of disease

Many children with acute leukemia have musculoskeletal complaints and non-specific hematologic abnormalities. A total of 10 children with acute leukemia and 10 with systemic juvenile rheumatoid arthritis were compared to delineate which early features could differentiate these diagnoses. Attention to evolving hematologic abnormalities and musculoskeletal findings may expedite diagnosis of these diseases.

Successful treatment of severe cytophagic histiocytic panniculitis with cyclosporine A

Cytophagic histiocytic panniculitis (CHP) can be a severe variant of Weber-Christian disease characterized by the histopathologic appearance of lobular panniculitis infiltrated by histiocytes containing blood cell fragments and by a clinical course with marked systemic features including multiorgan failure, hypertriglyceridemia, and coagulopathy, which may lead to death. Therapy of CHP includes standard treatment for panniculitis, such as antimalarials, plus immunosuppressives for more severe cases. The response to treatment, however, is unpredictable. In several recent reports, cyclosporine A has been successfully used to treat panniculitis. We report a patient and review the literature on CHP and the use of cyclosporine A as therapy. Published reports reveal that in instances of severe CHP when cyclosporine A was not given, 19 of 27 patients died (70% mortality). When severe CHP was treated with cyclosporine A, rapid remission was achieved in our patient and all five previously published cases (0% mortality). We believe cyclosporine A is the drug of choice in severe CHP and should be considered in all such patients.

Clinical assessment of the 1987 American College of Rheumatology criteria for rheumatoid arthritis

The 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis (RA) were clinically assessed. These criteria do not include findings of synovial fluid (SF) analysis and require no exclusion criteria. We have studied sequential patients with arthritis seen in four rheumatology centers in the Philadelphia area. Classifications by the ACR criteria were compared with our clinical diagnoses. Two hundred ninety eight patients were evaluated, 113 with RA and 185 with other diagnoses. Classifications as RA by the ACR criteria corresponded to our clinical diagnosis in 95% of the cases, corroborating the high sensitivity previously reported. However, we found a lower specificity (73%) than that reported (89%). False positive classifications as RA were found in 71% of patients with psoriatic arthritis, 48% of patients with SLE, and 31% of patients with gout. The specificity could be improved to 89% by excluding disorders with obvious distinguishing extraarticular features such as psoriasis or by SF findings of monosodium urate crystals. Awareness of these possible sources of confusion will further increase the teaching and epidemiologic value of these useful simplified criteria.

Pyomyositis: Report of Three Patients and Review of the Literature

Pyomyositis is the primary infection of skeletal muscles, accompanied by abscess formation in the suppurative phase but may be without a focal fluid collection in the presuppurative phase. We describe three patients, one with insulin-dependent diabetes mellitus, another with sickle cell disease, and the third a previously healthy child with varicella infection who developed pyomyositis. Ultrasound or magnetic resonance imaging suggested the diagnosis in each case. The patients were treated with intravenous antibiotic therapy and two required abscess drainage. The infection in the third resolved without surgical drainage. None of our patients had residual functional limitations. We believe that a high index of suspicion and prompt diagnosis can prevent complications from pyomyositis.

Myofascial Pain Unresponsive to Standard Treatment: Successful Use of a Strain and Counterstrain Technique with Physical Therapy

Chronic pain disorders, including fibromyalgia and myofascial pain syndrome often do not respond adequately to standard therapy. The cases reviewed herein suggest the strain and counterstrain (SCS) technique, described in 1981 by Jones, may be helpful in reducing pain and improving function in patients with localized myofascial pain syndromes. This was a case study and retrospective review of 20 patients who had had chronic pain for an average of 2.7 years and were treated with SCS for pain relief. For all these patients, prior medical treatment had failed to provide pain relief or return of function. The procedure is a fairly common osteopathic and chiropractic technique, which to our knowledge has not received any systematic evaluation. Areduction in pain and an increase in function of 50%-100% occurred in 19 of 20 patients immediately after SCS therapy. Partial improvement was maintained for 6 months in 11 of 20 patients, and 4 were still pain free. We believe that SCS techniques should be considered and evaluated further as adjunctive therapy for patients previously unresponsive to standard treatment for myofascial pain syndrome.

Autoimmune manifestations of the wiskott-aldrich syndrome

OBJECTIVE To describe and review the autoimmune features and typical manifestations of Wiskott-Aldrich syndrome (WAS). DESIGN Case series and review of the literature. SETTING Tertiary care medical center and pediatric referral center. PATIENTS The presentation, diagnosis, and management of two cases are reported. In addition to the typical features of WAS, the first patient had hemolytic anemia, arthritis, leukocytoclastic vasculitis, and colitis. The second patient had colitis and arthralgias. Detailed review of features and therapeutic options in WAS as exemplified by these two patients are presented. Both patients had bone marrow transplantation, the only definitive treatment for WAS. CONCLUSIONS WAS has variable clinical and autoimmune manifestations. Diagnosis must be suspected in a boy with small, decreased number of platelets and autoimmune problems or infections. Bone marrow transplantation is the only successful mode of treatment for all aspects of WAS.

Failure of anakinra treatment of pyoderma gangrenosum in an IBD patient and relevance to the PSTPIP1 gene

Pyoderma gangrenosum (PG) is a skin disorder affecting approximately 2%–5% of patients with inflammatory bowel disease (IBD). PG can also be part of PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum, and acne), which is an autosomal dominant disease caused by mutations A230T and E250Q in the threonine phosphatase-interacting protein 1 (PSTPIP1; CD2BP1) gene on chromosome 15. The PSTPIP1 mutations lead to elevated levels of interleukin-1b and have been successfully treated with the recombinant human interleukin-1 receptor antagonist, anakinra. Recently a microsatellite variation in the promoter region of PSTPIP1 has been also associated with Crohn’s disease (CD) and aseptic abscesses. We investigated the case of a 42-year-old male diagnosed with ulcerative colitis at the age of 31 who underwent ileal pouch anal anastomosis for medical failure (including failing cyclosporine and infliximab) with the postoperative complication of severe peristomal PG that resolved with stoma closure but then recrudesced 3 years later when he was again given a stoma for proximal small bowel to pouch fistulizing disease. His diagnosis was changed to CD but his severe, near circumferential peristomal PG was nonresponsive to steroid and infliximab treatment. We speculated that this patient may harbor a PSTPIP1 mutation and therefore be responsive to anakinra treatment. Peripheral blood B cells and Epstein–Barr virus (EBV)-transformed B cell lines were prepared from blood samples from pyoderma and IBD patients and non-IBD controls. Intestinal tissues of IBD patients were obtained at the time of surgery, and intestinal tissues of non-IBD individuals acquired from NDRI (National Disease Resource Interchange, Philadelphia, PA). Genomic DNA and total RNA were isolated with Qiagen (Chatsworth, CA) kits. We genotyped the two known PAPA syndrome-associated mutations of the PSTPIP1 gene, A230T and E250Q, using a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP method). No mutation was found for either single nucleotide polymorphism (SNP) in the study case, nor in seven additional IBD patients with pyoderma. To confirm the genotyping result and search for any other mutations in the gene, we directly sequenced a 1363 bp of PCR fragment including the entire amino acid coding sequences, 44 nt of 50 untranslated region (UTR) and 50 nt of 30 UTR. No mutation was detected from the sequenced regions. Recently, Andre et al detected three microsatellite variants (CCTG)4, (CCTG)5, and (CCTG)7 at nt 405 upstream of the translational start codon ATG. The longest form (CCTG)7 was associated with aseptic abscesses syndrome (AA). AA is a relapsing inflammatory condition that is associated with IBD in 66% of cases (mainly CD in 57%), and also with neutrophilic dermatosis (ND) in 20%. Similar to a previous study, the study case was affected with PG and also IBD. We directly sequenced 370 bp of a PCR fragment containing the microsatellite repeats, and found that the study case was homozygous for (CCTG)5 allele, i.e., did not have the allele shown to be associated with AA. Summarizing the results described above, we conclude that the study case did not carry any known mutation in the entire cDNA nor the promoter region of the PSTPIP1 gene. Accordingly, the patient was found to be nonresponsive to anakinra treatment when given a dose of 100 mg/day for over 8 weeks. However, we hypothesized that the gene PSTPIP1 may play a role in pyoderma pathogenesis through mechanisms other than genetic mutation. We therefore further examined the gene expression using EBV-transformed Bcell lines generated from the study case and other IBD patients blood samples. We consistently observed a higher level of PSTPIP1 transcripts in the study case and other IBD patients compared to non-IBD family members and unrelated healthy controls. The observed difference was not due to the EBV transformation based on the comparison of EBV-transformed B-cell lines with peripheral blood B cells from the same individuals (Fig. 1A). From reverse-transcription polymerase chain reaction (RTPCR) analysis of PSTPIP1 transcription, we detected two additional PCR products indicated as B and C in Figure 1A. The result of direct sequencing of these PCR products showed that fragment B had 254 nt of the AHCYL1 (adenosylhomocysteinase-like 1) cDNA sequence from amino acid #333 (exon 10) to #418 (exon 13); and the fragment C had 225 nt of the 30 UTR (nt #4015 to #4230) of the SMG5 (Smg-5 homolog, nonsense mediated mRNA decay factor) cDNA sequence. Both SMG5 and AHCYL1 are located on human chromosome 1, while PSTPIP1 is located on chromosome 15. Recently, a chromosome t(1;15)(p22;q22) translocation has been shown to be a loss of chromosome material proximal to the breakpoint on chromosome 15 contains the PSTPIP1 gene. The breakpoint is on 1p22, while gene AHCYL1 is located on 1p13.3 and SMG5 1q22. The coamplification of PSTPIP1 with SMG5 was further examined by PCR with a primer pair of PSTPIP1 (forward) and SMG5 (reverse). As shown in Figure 1B, a strong PCR amplification was noted in the study case as well as another UC patient (888-57), but no or very weak PCR products from two other Copyright VC 2011 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.21684 Published online 15March 2011 inWiley Online Library (wileyonlinelibrary.com).

Lyme disease. Difficulties in diagnosis and management.

LB is a multisystem illness caused by the spirochete B. burgdorferi. As with other spirochetal diseases, LB evolves in stages. Some manifestations are the result of persistent infection, whereas other symptoms are a consequence of immunologic changes secondary to the infection. Most disease manifestations are not specific to this illness. In addition, in endemic areas, almost 100% of the tick vector, the Ixodes species, are infected and the incidence rate of LB is as high as 1%. Because of these factors, the illness is overdiagnosed and overtreated. We have reviewed the current state of diagnosis and treatment of LB as well as questions that arise during the management of this illness.