From the Dermatologikum Hamburg: Quiz

A 7-year-old girl was presented by her parents with a nodule on the right leg. The lesion had been present for a few weeks and had slowly increased in size. At the time of presentation the lesion measured 6 mm in diameter and it was neither painful nor itchy ( Figure 1A). Skin examination revealed two additional smaller red papules on the same leg (Figure 1B). A biopsy was taken from the lesion pictured in Figure 1A.Histopathologic changes are presented in Figures 2A-E. What is your diagnosis? Would you ask for any special stains or other investigations for this patient?

. Erythematous lesions on the forearm, some with crusts.  With the features mentioned above the differential diagnoses considered were amyloidosis, erythropoietic protoporphyria, and lipoid proteinosis. Congo red did not stain the deposits, making amyloidosis unlikely. In lipoid proteinosis, the deposits usually surround the eccrine secretory coils also, a feature absent in this case. Moreover, lipoid proteinosis has an onset in infancy with a characteristic cry of the child due to deposits in the larynx and oral cavity. In erythropoietic protoporphyria, PAS-positive, brightly eosinophilic, concentric deposits are seen around the blood vessels without involvement of the eccrine coils, similar to the present case.
In clinicopathological correlation, the thickening of the skin is a consequence of deposition of protoporphyrins, commonly due to a rare genetic deficiency of the enzyme ferrochelatase [1,2]. It manifests during early childhood in the form of burning, erythema, and edema following photoexposure. The lesions heal with residual "icepick" scars over the face and knuckles. Scleroderma-like thickening may also be encountered later in the course of the disease.
When a diagnosis of EPP is suspected, blood, stool, and urine should be examined for porphyrins. Usually, blood
In this patient, the history of photosensitivity combined with red and painful skin lesions should raise the suspicion of EPP. However, the clinical differential diagnoses include  al reported on a patient with late onset EPP in 1985 and, since then, around 12 additional patients with adult onset EPP have been described in the literature [11][12][13][14][15][16][17][18][19]. Eight of these cases were associated with hematological malignancies such as myelodysplastic syndrome (MDS) (often the sideroblastic anemia subtype) or myeloproliferative diseases [2,12,14,15,17,[20][21][22]. Two of these patients developed liver dysfunction [2,18] in the course of their disease. Elevated levels of porphyrins in urine signify the onset of hepatic involvement and are very useful in monitoring the disease, together with porphyrin isomer ratios [3]. In this patient, the free protoporphyrin in blood was 18630 nmol/L (normal: 9-89 nmol/L), which was markedly elevated. Zinc protoporphyrin was 68.1 μmol/L and total protophyrin was 19192 nmol/L, both being clearly higher than normal. These findings are consistent with a diagnosis of erythropoietic protoporphyria. Urine examination revealed normal coproporphyrin levels, but an elevated coproporphyrin isomer I (43.8%) and a depressed coproporphyrin isomer II (56.2%).
Even without porphyrinuria, this alteration in isomer ratio is an early sign of hepatic involvement and such patients derive benefit from prophylactic therapy.
Porphyrias are a group of metabolic diseases that result from aberration in the heme biosynthesis pathways [4,5]. Deposits of protoporphyrin in skin leads to acute photosensitivity. Ultraviolet light absorption by protoporphyrin in plasma and erythrocytes when blood circulates through the dermal vessels results in formation of free radicals. Erythrocytes become unstable and injury to the skin is induced [8].
A significant increase in the hepatobiliary excretion of protoporphyrin can damage the liver through both cholestatic phenomena and oxidative stress predisposing the individual to hepatobiliary disease of varying severity [9,10].
When the onset of disease is in adulthood, as it was the case in this patient, it is important to note that it may be associated with myelodysplastic syndromes and other hematologic malignancies [3,4]. An acquired somatic mutation or deletion of the ferrochelatase gene is the purported causation. It is imperative to check the hematologic parameters of the patient. However, no such association was identified in the patient presented here and his blood counts were normal. Even though late onset EPP is very rare and usually associated with hematological malignancy, cases without such association have also been observed. Murphy et