Scurvy, all the faces you can see: our experience and review of the literature

Abstract

Background: In the recent past an incremental incidence of scurvy has been reported in the pediatric population, especially in children with neuropsychiatric disorders and a selective diet. Musculoskeletal manifestations, such as limp and refusal to walk, usually represent the main causes of access in the emergency room. Nowadays, new patterns of manifestations have been demonstrated, such as hematological and cardiological changes including pulmonary hypertension, rarely resulting in potential lethal complications.

Case presentation: We describe five pediatric patients affected by developmental delay or autism, with a restrictive diet, diagnosed with scurvy during the hospitalization: 3 pre-school aged boys presenting with typical clinical presentation, due to severe malnutrition; a 6-year-old girl with refusal to walk and a very high titre of inflammatory markers, without typical signs of scurvy; a 4-year-old boy with severe pulmonary hypertension, rarely related to vitamin C deficiency. In all the cases, a prompt resolution of the symptoms after the administration of vitamin C has been observed, confirming the diagnosis.

Conclusion: At present, scurvy is a more contemporary condition than previously thought. It is fundamental to recognize both typical and atypical manifestations to avoid delay of diagnosis or rarely life-threatening complications.

Keywords: Anemia; Children; Inflammatory markers; Pediatrics; Pulmonary hypertension; Scurvy; Vitamin C.

Fig. 1

Step-by-step diagnostic algorithm for scurvy Step 1, dietary history and risk factors: it is mandatory to evaluate any possible restrictive or selective diet disorder, especially in patient with autistic spectrum disorder and other neuropsychiatric disorder or any possible condition associated with malabsorption of vitamin C; Step 2. Clinical evaluation: (A) Typical presentation: typical signs of scurvy includes irritability, inappetence, petechiae, ecchymosis, corkscrew hair, swelling and bleeding gums and musculoskeletal signs; (B) Atypical presentation: atypical symptoms may include anemia, elevated inflammatory markers, pulmonary hypertension and gastrointestinal bleeding; in this case it is important to evaluate the general condition of the patient and if necessary stabilize him before proceeding on further diagnostic evaluations; Step 3. Laboratory testing and treatment: in both case, in the suspicion of scurvy a treatment with vitamin C should be started, checking the plasma vitamin C levels before; Step 4. Clinical Response and Diagnosis: if symptoms resolve and plasma vitamin C is deficient, the diagnosis of scurvy is confirmed; if symptoms resolve but plasma vitamin C is normal, the diagnosis is still confirmed due to the fact that plasma vitamin C levels does not reflect the effective distribution of the tissular vitamin C and the prompt resolution after the start of the treatment is the major diagnostic criterion; if symptoms persist despite normal plasma vitamin C, Consider other causes. Step 5 Identifying underlying conditions: if a patient presents with both typical and atypical signs, and atypical symptoms persist after the resolution of typical signs with vitamin C treatment, scurvy is likely associated with an underlying condition that must be investigated further; If symptoms persist despite normal plasma vitamin C levels, other differential diagnoses must be considered *Figure 2 resume possible other causes to take into consideration and the diagnostic evaluation considering the various symptoms

Fig. 2

Differential diagnosis for each symptom associated with limp/refusal to walk Respectively: (1) Severe malnutrition: in this case the vitamin deficiency could be a consequence of many organic or non-organic causes of a severe, prolonged, malnutrition; a complete nutritional assessment includes: plasma iones, vitamins, total proteins, albumin, iron assessment; (2) Microcytic anemia: iron deficiency should be considered as the main possible cause; intestinal malabsorption, chronic inflammatory diseases and tumors may be taken into consideration; further, as confirmed by literature, a vitamin C deficiency could be responsible for this condition; in the absence of alteration of the iron assessment, other specific exams should have been performed to eliminate red blood cells membrane disorders or genetic conditions; (3) Elevated inflammatory markers: many different conditions may be hidden and clinical exam and imaging are mandatory: systemic symptoms as fever are usually present in case of osteomyelitis or septic arthritis, together with specific clinical signs as swelling at the site of the infection; similarly for AIG; usually radiographic exam allows to eliminate the presence of osteo-muscular tumor or fractures and rarely, if other causes are not identified, an IRM should be considered and CNO could be diagnosed. Thus, when clinical findings are suggestive for scurvy, a vitamin C treatment should be started. (4) Pulmonary hypertension: rare condition in pediatric age due to different groups of conditions: left heart diseases (congenital or acquired), pulmonary diseases (developmental lung disorders, emphysema, obstructive or restrictive diseases, tumors), pulmonary artery obstruction, multifactorial mechanism (metabolic, hematological, infective, systemic disorders) or idiopathic. Cardiac catheterization is considered the gold standard for diagnosis of PH, however, it is an invasive procedure usually deferred until initiation of targeted PH therapy is under consideration. The initial evaluation consists of an accurate collection of the personal history and a clinical exam; thus, an EKG, a transthoracic echocardiography and a thorax radiography should be performed

Fig. 3

Comparison between cardiological situation at the admission and after 5 days of therapy (1) At the diagnosis, the patient presented a severe PH (PAPs 75–80 mmHg) (B) associated with signs of right hearth failure as right ventricular dilatation and dyskinesia (A) (2) After 5 days of i.v. therapy with ascorbic acid he presented normal heart anatomy and function (C) and a complete resolution of the PH, with a PAPs 20–25 mmHg (D)