An 8-month old with erythema nodosum – clinical case report

nodosum pathology in childhood big antigen Aim of the work was to make differential analysis of the described case with developed multiple, nontender, depth erythematose papules in the epidermis-dermis (like nodules) on the head, trunk, extremities, associated with adopted cow’s milk-based formula intake. Methods and results. The next methods, as deep literature review and differential analysis, helped to underline probable pathogenetic mechanisms of such type of allergy skin symptoms, to diagnose Erythema nodosum in the child. Conclusion. This clinical case showed presence of rare clinical food allergy skin symptoms that have mixed mechanisms of onset. Further studies of the gear of onset and histology speci ﬁ city are needed.

There were papules approximately 3 to 5 mm in diameter free within the epidermis and superfi cial layers of the derma. Their color was deep red, they were firm, spheriform, nontender, slightly mobile. Palpation elicited no discomfort. They were localized over the face, beck, on the lower extremities, mostly on the shins (Fig. 1 on the color tab №4). Abdomen, scalp and upper extremities were covered minimally. They were not fi xed to skin or subcutaneous tissue below.
Differential diagnosis. When considering the skin symptoms most important aspects were: the number, fi rmness, localization, color and absence of itching, and no effect from antihistamine drug. Because the most part of the lesions were on the shin, erythema nodosum was initially considered as a primary diagnosis. It was important to distinguish between infectious, infl ammatory and neoplastic causes [1,12]. Multiple causes of EN related to infection have been described, including streptococcal infection, tuberculosis, coccidioidomycosis, and histoplasmosis, as well as infections caused by species of bartonella, yersinia, salmonella, mycoplasma, chlamydia, and leptospira [12]. Acute urticaria, insect bites were included into the differential diagnosis list too.
In infectious EN intoxication and change of the general state of health are usually presented as fever, low appetite, hepatosplenomegaly, CBC change, serum specifi c antibodies levels. In a special case of leprosy, syphilis and leishmaniasis other specifi c symptoms are seen as usual [1,2,12]. Our patient didn't have such symptoms. Taking into account situation with tuberculosis the boy's history was additionally analyzed. Patient's parents, the boy were vaccinated with BCG vaccine and had scar on the shoulder. Child's general condition, other organs, except skin, were not affected. Metastatic neuroblastoma was excluded because it is commonly associated with internal organs affection [12].
The patient did not have a recent history of pharyngitis or scratches, bites. Child and his clothes were carefully examined, other family members were healthy. EN elements did not have any bite signs. Moreover his specifi c IgG and IgM to Cytomegaloviral infection were studied, result was negative. Important considerations in a young child are lymphoma and sarcoma, which may be presented as multiple cutaneous nodules. But as malignant, as fungal nodules usually have indistinct borders, are often fi xed with underlying tissues. They heal with scars. Our patient had mobile nodules, they healed without atrophy or scarring. Acute urticaria was excluded too. No urticaria elements were presented, child didn't have pruritis, pigmentation. Darier's sign was negative. There was no effect from the antihistamine drug intake. EN may be due to a variety of underlying infectious or otherwise antigenic stimuli. Both neutrophilic infl ammation and granulomatous inflammation are implicated in the pathogenesis [6,12]. This fact gave us opportunity to suspect non infectious causes of the EN in this case. It was shown that in one third of cases cause of the EN can't be founded [1][2][3]5]. Patient's history gave us information about possible cause of the disease onset: progression and redness increase was associated with adopted cow's milk-based formula intake. Common clinical sighs of food intolerance makes distinguishing immunological and nonimmunological mechanisms diffi cult [10,13]. On the other hand skin symptoms appeared spontaneously only 2-3 weeks before visit to the doctor. In contrast, rather confused was duration of the artifi cial feeding of the child -about 4-5 months. Because, as usual, milk protein allergy presents from a few days to a few weeks after the introduction of milk protein into the diet. Sensitization period usually takes some time, but can it be about 3-4 months? Additional history data showed that several weeks ago easily-digested instant cereal-based preparations were added to the child's menu. Taking into account literature data about presence of the cross reactivity between milk and wheat proteins, we suspected some contribution of the cereals in the disease onset [9,11]. These facts explained given time frames. The patient had increased serum level of the common IgE and no evidence of infl ammation or other abnormalities. Of the diagnoses that remain, food hypersensitivity EN is the most likely. With this disorder all lab data are usually normal except specifi c and common IgE levels. One needs to consider the skin allergy testing should be done lately because of the age or because of the condition? Specifi c IgE levels were estimated. It was increased more than in 80 times to cow proteins and in 16 times to meat. It was interesting but patient didn't have elevated IgE to wheat. Based on the results of lab test, the diagnosis of food allergy was made. IgE and non-IgE mechanism were suspected (to milk and wheat correspondently). Amino-acid formulas were prescribed for the patient for 2 weeks with shift to partial hydrolysate. Cereal-Based Gluten-Free Food was prescribed too. For topical use emollient was recommended for frequent application (5-6 times/day). View of the patient's legs is given on the Fig. 2 on the color tab №4.
Unfortunately parents refused to make biopsy of the nodules and complete differential diagnosis was not fi nished. Histiocytoses are a group of disorders involving An 8-month old with erythema nodosum -clinical case report, literature review the proliferation and accumulation of cells which can have manifestation with polymorphous cutaneous eruption over the whole body. As it was in our patient, the clinical course of Histiocytoses is usually benign and self-limited. The aetiology in paediatrics is still unclear. Virus-induced local immune alternation in the transformation of the histiocytosis has been postulated [4]. But in this case eruption onset was associated with easily-digested instant cereal-based preparations introduce and it increase was associated with adopted cow's milk-based formula intake.

Discussion
In this case, based on the patient's history, on the conditions of resolution of symptoms when adopted cow's milk-based formula was removed, food allergy was suspected. Literature review showed few data concerning EN in children, mostly it related to the hypersensitivity reactions in adults.
Specifi c clinical skin symptoms and order of their appear made us to suspect EN. N.F. Filatov named this illness «disease in stockings» and our patient had maximal deep papulas/nodules localisation on shins. N.I. Nisevich reported about allergic eruptions looking like EN for differential diagnosis of the infectious diseases [3].
Prof I.V. Bogadelnikov indicated that sizes of the nodules can be from 0.5 to 3 cm, our patient had nodules 0.3-0.5 up to 1 cm. Although he denoted that usually these elements undergo evolution, change color [1]. But our patient's eruption just gradually disappeared, turned pale. Furthermore Prof I.V. Bogadelnikov indicated that evolution is not permanent and other clinical variant of the EN can be [1].
The one should be noted: patient had painless eruptions, which is usually seen in such kind of the skin disorders. That fact gives opportunity to make concerning about this clinical specifi cities of the allergic EN in children.
To our mind this patient's food hypersensitivity EN had cell-mediated or mixed IgE-and cell-mediated mechanism of onset. Habif T. et al. 2011 indicated that EN usually occurs due to the hypersensitivity reactions in the condition of the massive antigen stimuli. Other systems are not changed, lymphadenopathy can be founded [7]. It is interesting to note that EN in this patient started to recover gradually only after diet correction and emollient applying. Total recover became only in 3 weeks. In such situation gluten hypersensitivity was suspected. G. Kristjánsson et al (2007) showed that mucosal infl ammatory response similar to that elicited by gluten was produced by CM protein in about 50% of the patients with coeliac disease [9]. Effectiveness of the recommended diet with amino-acid formula and cereal-based gluten-free food confi rmed our suspicion.
This case gave us opportunity to underline EN as probable clinical form of the food allergy with mixed IgE-and nonIgEmechanism. Further studies of the gear of onset and histology specifi city are needed.