Deficiency of adenosine deaminase 2: a genetic autoinflammatory disorder mimicking childhood polyarteritis nodosa.

A girl in the early adolescent age group presented with multisystem manifestations in the form of periodic fever, recurrent abdominal pain, hypertension, seizure, skin lesions over the chest and gangrene over the left ring and middle fingertips. Her condition had remained undiagnosed for 11 years. On evaluation, she had features of polyarteritis nodosa (PAN) (multiple aneurysms, symmetric sensorimotor peripheral neuropathy, superficial ulcers, digital necrosis, myalgia, hypertension and proteinuria). As childhood PAN is a phenocopy of adenosine deaminase 2 with a different management strategy, whole-exome sequencing was performed, which revealed a pathogenic variant in ADA2 gene. The child was treated with TNF alpha inhibitors and showed improvement in the Paediatric Vasculitis Activity Score. The paper highlights the gratifying consequences of correct diagnosis with disease-specific therapy that ended the diagnostic odyssey, providing relief to the patient from debilitating symptoms and to the family from the financial burden of continued out-of-pocket health expenditure.

Cutaneous nodular polyarteritis presenting as refractory ulcers on both lower extremities: A case report.

BACKGROUND: Cutaneous polyarteritis nodosa (cPAN) is a systemic disease that is limited to the skin. cPAN usually presents with cutaneous reticular cyanotic, erythematous and palpable nodules, and cutaneous ulcers.Research has indicated that the use of hormones and immunosuppressive drugs can delay ulcer healing and associated neuropathy, and also elevate the risk of disease recurrence upon their reduction or withdrawal. Therefore, it is a necessary to find a safe and effective approach that minimize hormone side effects in ulcer treatment. CASE PRESENTATION: The patient, a 48-year-old female of Han Chinese ethnicity, has suffered from recurrent erythema nodosum on both lower limbs for 8 years. The condition was aggravated by skin breakdown over the last 3 months. Despite multiple treatments, the patient's condition did not improve significantly, leading to the exploration of a combined approach of traditional Chinese and Western medicine. Following six months of combined traditional Chinese and Western medicine treatment, t the patient's newborn erythema and ulcers on both lower limbs did not reappear, and the ulcers gradually decreased in size and the erythema disappeared. The patient took the TCM regularly until April 15, 2023, when the ulcers were completely healed. Three months after the patient stopped taking TCM, the ulcers had completely healed with no recurrence, as observed during the follow-up visit on July 14th, 2023. CONCLUSION: Traditional Chinese Medicine Combined with Low-Dose Hormones May Effectively Treat Bilateral Lower Extremity Skin Ulcers Caused by Cutaneous Polyarteritis Nodosa.

Efficacy of rituximab in refractory polyarteritis nodosa: a case report.

Polyarteritis nodosa (PAN) is a systemic vasculitis affecting medium and small-sized vessels resulting in multiple organ involvement. Refractory PAN requires a different therapeutic approach. We herein report the case of a 42-year-old male presenting a non-virus-related refractory PAN with a favorable outcome on rituximab. He presented significant weight loss, muscle weakness, peripheral axonal neuropathy, and medium-sized cutaneous vessel necrotizing vasculitis. The patient received high-dose corticosteroids and cyclophosphamide with no significant clinical improvement while developing adverse side effects such as hypertension and diabetes. Rituximab was prescribed as an alternative therapy at 1000 mg on day 0 and day 15. This allowed for complete and rapid control of disease activity with regression of cutaneous injury and substantial improvement of neurological symptoms. In conclusion, using chimeric anti-CD20 monoclonal antibodies, such as rituximab, although rarely reported in refractory non-virus-related PAN, may be an effective alternative therapy, as portrayed in our case.

The "Viral" Form of Polyarteritis Nodosa (PAN)-A Distinct Entity: A Case Based Review.

Classic polyarteritis nodosa (PAN) is a vasculitis with systemic manifestations that is characterized by inflammatory and necrotizing lesions affecting medium and small muscular arteries, most frequently at the bifurcation of the vessels. These lesions lead to the formation of microaneurysms, hemorrhaging ruptured aneurysms, thrombosis, and, consequently, ischemia or organ infarction. Background and Objectives: We present a complex clinical case of a patient with a late diagnosis of polyarteritis nodosa with multiorgan involvement. Materials and Methods: The 44-year-old patient, in an urban environment, presented on her own in the emergency room for acute ischemia phenomena and forearm and right-hand compartment syndrome, requiring surgical decompression in the Plastic Surgery Clinic. Results: Significant inflammatory syndrome is noted, alongside severe normocytic hypochromic iron deficiency anemia, nitrogen retention syndrome, hyperkalemia, hepatic syndrome, and immunological disturbances: absence of cANCA, pANCA, anti Scl 70 Ac, antinuclear Ac, and anti dDNA Ac, as well as a low C3 fraction of the plasmatic complement system. The morphological aspect described in the right-hand skin biopsy correlated with the clinical data supports the diagnosis of PAN. Conclusions: The viral form of PAN seems to be individualized as a distinct entity, requiring early, aggressive medication.

Polyarteritis nodosa: an evolving primary systemic vasculitis.

Polyarteritis nodosa (PAN) is a primary form of vasculitis characterized by inflammation of primarily medium-sized arteries. Several key events have shaped the current spectrum of the disease including the separation of a subgroup with microscopic polyangiitis, the discovery of the association of hepatitis B, and the discovery of adenosine deaminase 2 deficiency (DADA2). With the discovery of secondary causes of PAN and changing nomenclature, the incidence of PAN has declined over time. Common manifestations include constitutional symptoms, skin involvement, peripheral neuropathy, gastrointestinal disease, and renal involvement. DADA2 is a genetic cause of medium vessel vasculitis that is important to distinguish from primary PAN as treatment with TNF inhibitors can prevent morbidity and mortality in those with a vasculitis phenotype. Treatment of systemic primary PAN involves the use of systemic immunosuppressive therapy largely guided by the severity of disease. With current treatment regimens, the prognosis has changed from a once uniformly fatal disease to a 5-year survival rate above 80%.

Identifying risk and prognostic factors in polyarteritis nodosa patients with digital gangrene.

BACKGROUND: Many patients with polyarteritis nodosa (PAN) complicated by digital gangrene have poor outcomes and related research information is limited. Our aim is to identify the associated risk and prognostic factors in PAN patients with digital gangrene. PATIENTS AND METHODS: We conducted a retrospective study of 148 PAN patients admitted to Peking Union Medical College Hospital from Octorber 2001 to December 2018. Forty-seven (31.8%) PAN patients had digital gangrene. The average age was 40.4 ± 17.9 years. RESULTS: The presence of digital gangrene was correlated with current smoking (P = .008, odds ratio [OR] 2.99, 95% CI, 1.33-6.73), eosinophil elevation (P = .003, OR 4.21, 95% CI, 1.62-10.91) and elevated leukocytes (P = .001, OR 4.26, 95% CI, 1.86-9.78). Thirty-two (68.1%) gangrene patients received methylprednisolone pulse therapy and all of these patients were treated with cyclophosphamide. Nine patients suffered irreversible organ injury and 2 died. Survival analysis showed higher serum C-reactive protein (CRP) was associated with poor prognosis in patients with gangrene (log-rank P = 0.042 and generalized Wilcoxon P = .020). CONCLUSIONS: PAN patients with current smoking and eosinophil elevation were more prone to digital gangrene and a high serum CRP level predicted poor outcomes. The CRP level should be efficiently controlled to ensure a good prognosis.

Polyarteritis nodosa presenting with posterior reversible leukoencephalopathy syndrome.

A man in his 20s presented following a generalised tonic-clonic seizure on a background of a recent diagnosis of hepatitis B (HBV). During admission, he was severely hypertensive and imaging findings confirmed a diagnosis of posterior reversible leukoencephalopathy syndrome (PRES). The patient subsequently developed multiorgan involvement with an axonal sensorimotor neuropathy, vascular cutaneous lesions and multiple bilateral renal and splenic infarcts. Based on the 2012 Revised International Chapel Hill Consensus Criteria, a diagnosis of polyarteritis nodosa (PAN) with secondary PRES was made. The patient was given intravenous methylprednisolone, followed by a prolonged course of oral prednisolone, and tenofovir antiviral therapy to target HBV seroconversion. He made a good neurological recovery with resolution of imaging changes. This case highlights the importance of a low threshold for systemic screening for young patients presenting with PRES secondary to uncontrolled hypertension and the importance of viral screening, particularly for HBV.

Polyarteritis Nodosa with Cytomegalovirus Enteritis and Jejunoileal Perforation: Report of a Case with a Literature Review.

Polyarteritis nodosa (PAN) is a rare systemic necrotizing vasculitis affecting small- to medium-sized arteries. The most common gastrointestinal manifestation of PAN is postprandial abdominal pain from mesenteric arteritis causing bowel ischemia. When transmural ischemia develops, there may be ischemic necrosis and perforation of the bowel wall, which are life-threatening. Severe, life-threatening gastrointestinal involvement is relatively rare in pediatric PAN and may require different management in adult patients. We report a pediatric PAN case in a patient who presented with acute abdominal pain and superimposed cytomegalovirus enteritis with jejunoileal perforation. The patient improved with emergency small intestinal resection followed by conventional immunosuppressive drugs of a corticosteroid and cyclophosphamide, and anti-viral drugs. Before increasing the immunosuppressive drug dosage, initial screening of infectious cytomegalovirus and comprehensive evaluation for surgical conditions are essential in pediatric PAN with severe gastrointestinal involvement. Early aggressive treatment for acute abdomen is useful in reducing morbidity and mortality in pediatric PAN.

Use of biologics to treat relapsing and/or refractory polyarteritis nodosa: data from a European collaborative study.

OBJECTIVES: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN). METHODS: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease. RESULTS: Forty-two patients with PAN received a total of 53 biologic courses, including TNF-α blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases and other biologics in 10 cases. TNF-α blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission, partial response, treatment failure and treatment discontinuation due to severe adverse events occurred in, respectively, 40%, 13%, 40% and 7% of patients receiving TNF-α blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the three biologics, leading to early biologics discontinuation in only three cases. CONCLUSION: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings.

Mycophenolate mofetil in the treatment of childhood systemic polyarteritis nodosa.

Polyarteritis nodosa (PAN) is a medium vessel vasculitis with necrotising vascular changes along with multisystemic involvement. Due to variable initial presentations, diagnosis of systemic PAN in children requires a comprehensive work up. In addition, systemic PAN needs an aggressive therapy. Mycophenolate mofetil is an emerging newer alternative for the treatment of PAN. We report a case of childhood systemic PAN who initially presented with subtle signs like reduced sensation over lateral foot, non-deforming arthritis and multiform rashes. After comprehensive aetiological work up, nerve biopsy and supporting evidence clinched the diagnosis. Vasculitis in children presenting with benign subtle signs is sometimes a diagnostic challenge to clinicians. Our case highlights the importance of lateral thinking while dealing with non-specific multisystemic signs. Evidence of successful treatment of PAN with mycophenolate mofetil is gradually being built up. It is also described to result lower relapse and increased treatment free survival rate.

Efficacy and safety of treatments in cutaneous polyarteritis nodosa: A French observational retrospective study.

BACKGROUND: Cutaneous polyarteritis nodosa is a form of medium-sized vessel vasculitis. Despite a disabling and prolonged course, data on treatment efficacy and safety remain scarce. OBJECTIVES: We aimed to describe treatment efficacy and safety in patients with cutaneous polyarteritis nodosa. METHODS: This multicenter retrospective, observational study, recorded clinical and biologic data together with treatments received. The primary outcome was the rate of complete response at month 3. Secondary outcomes assessed drug survival and safety. RESULTS: We included 68 patients who received a median of 2 therapeutic lines (interquartile range, 1-3). Overall, complete response was achieved in 13 of 42 (31%) patients with colchicine, 4 of 17 (23%) with dapsone, 11 of 25 (44%) with glucocorticoids (GCs) alone, 1 of 9 (11%) with nonsteroidal anti-inflammatory drugs, 11 of 13 (84%) with GCs+azathioprine, and 7 of 15 (47%) with GCs+methotrexate. GCs+azathioprine had the best drug survival (median duration, 29.5 months; interquartile range, 19.5-36.0). Response at month 3 was decreased with peripheral neurologic involvement (odds ratio, 0.19; 95% confidence interval, 0.03-0.81; P = .04). Overall, the rate of treatment-related adverse events was 18%, which led to the discontinuation of treatment in 7% of patients. LIMITATION: Retrospective study. CONCLUSION: Colchicine seems to confer good benefit-risk balance in cutaneous polyarteritis nodosa without peripheral sensory neuropathy. GCs+azathioprine seem the best treatment in the event of relapse.