Indian Journal of Dermatology
: 2022  |  Volume : 67  |  Issue : 5  |  Page : 579--582

Could “islets of sparing” be a clue for neutral lipid storage disease with ichthyosis in patients with congenital ichthyosiform erythroderma?

Filiz Topaloglu Demir1, Baran Cayhan2, Cagla Karaoglan3, Zafer Turkoglu2, Nesimi Buyukbabani4, Mesut Ayer5, Bugrahan Duz6, Bulent Uyanık7,  
1 Medipol University, Faculty of Medicine, Dermatology Clinic, Istanbul, Turkey
2 Basaksehir Cam and Sakura City Hospital, Dermatology Clinic, Istanbul, Turkey
3 Bakırköy Dr. Sadi Konuk Education and Research Hospital, Pathology Clinic, Istanbul, Turkey
4 Istanbul University, Faculty of Medicine, Pathology Clinic, Istanbul, Turkey
5 Basaksehir Cam and Sakura City Hospital, Hematology Clinic, Istanbul, Turkey
6 Haseki Education and Research Hospital, Medical Genetics Clinic, Istanbul, Turkey
7 Bezmialem Vakıf University, Faculty of Medicine, Medical Genetics Clinic, Istanbul, Turkey

Correspondence Address:
Baran Cayhan
Basaksehir Cam and Sakura City Hospital, Basaksehir/Istanbul


The prevalent form of ichthyosis in neutral lipid storage disease (NLSDI) is nonbullous congenital ichthyosiform erythroderma (CIE) characterized by fine, whitish scales on erythematous skin over the whole body. Here, we report a late-diagnosed, 25-year-old woman with NLSDI presenting with diffuse erythema and fine whitish scales throughout the body with patches of apparently normal skin, “islets of sparing” on her lower extremities. We observed that the size of the normal skin islets changed with time, and even the entire lower extremity was covered with erythema and desquamation like the rest of the body. Frozen section histopathological examinations were made from lesional skin and normal-looking skin; no difference was observed in terms of lipid accumulation. The only noticeable difference was the thickness of the keratin layer. In CIE patients, observation of patches of apparently normal skin or “islets of sparing” might be a clue for NLSDI to be distinguished from other CIE conditions.

How to cite this article:
Demir FT, Cayhan B, Karaoglan C, Turkoglu Z, Buyukbabani N, Ayer M, Duz B, Uyanık B. Could “islets of sparing” be a clue for neutral lipid storage disease with ichthyosis in patients with congenital ichthyosiform erythroderma?.Indian J Dermatol 2022;67:579-582

How to cite this URL:
Demir FT, Cayhan B, Karaoglan C, Turkoglu Z, Buyukbabani N, Ayer M, Duz B, Uyanık B. Could “islets of sparing” be a clue for neutral lipid storage disease with ichthyosis in patients with congenital ichthyosiform erythroderma?. Indian J Dermatol [serial online] 2022 [cited 2023 Mar 21 ];67:579-582
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Full Text


Neutral lipid storage disease with ichthyosis (NLSDI) is a rare, nonlysosomal, autosomal recessive triglyceride storage disease associated with systemic accumulation of triacylglycerol (TG) in many tissues, especially in the skin, muscle, liver, and leukocytes.[1],[2] Here, we present a late-diagnosed woman with NLSDI presenting with congenital ichthyosiform erythroderma (CIE) with transient normal-looking skin islets, sensorineural hearing loss, hepatosteatosis, and myopathy.

 Case Report

A 25-year-old female patient was admitted to our clinic with a complaint of widespread scaling and dryness. The parents of the patient were second-degree consanguineous. Similar findings were found in both siblings, and all had a history of collodion membrane at birth. In the dermatological examination, widespread erythema and fine desquamation were detected in all body areas, except for apparently normal skin islets on both lower extremities [Figure 1]a. It was observed that the size of these islets on the lower extremities changed with time, and even the entire lower extremity was covered with erythema and desquamation like the rest of the body in three months [Figure 1]b. The patient had these transient lesions for 11 years, and her 19-year-old sister also had this phenomenon appearing recently in the lumbar region.{Figure 1}

Blood tests were normal except for serum creatine phosphokinase and lactate dehydrogenase. A second-degree hepatosteatosis on abdominal ultrasonography and mild sensorineural hearing loss, especially to high-frequency sounds, were detected. Deltoid 4/5, triceps 4/5, biceps 5/5, hand extensors 5/5, iliopsoas 3/5, quadriceps femoris 4/5, gastrocnemius 5/5, and foot extensors 5/5 detected in muscle strength examination; also, there was proximal muscle weakness in the lower extremities. Normal conduction in sensory and motor nerves and moderate myogenic involvement were stated in electromyography. Muscle biopsy was not performed. In ophthalmologic examination, blepharitis, bilateral esotropia, ectropion, and lagoftalmia were detected. Widespread vacuoles in neutrophils, eosinophils, and monocytes (Jordan's anomaly) were seen in peripheral blood smear [Figure 2]. Frozen examination of skin biopsy showed compact hyperkeratosis, mild acanthosis, and discrete vacuolization of basal keratinocytes, sweat glands, and mild superficial perivascular lymphohistiocytic infiltrate in the papillary dermis. Scharlach and Oil Red-O stains clearly and elegantly demonstrated the lipid content of these discrete vacuoles [Figure 3]. The vacuoles had a distinct distribution characteristic: their density increased towards the ends of the rete ridges. The patient was diagnosed with NLSDI based on these clinical, laboratory, and histopathological findings. Her siblings were examined after the diagnosis was finalized. CIE, grade 1 hepatosteatosis, sensorineural hearing loss, Jordan's anomaly, and lipid accumulation in frozen skin biopsy were detected in her 22-year-old sister. Furthermore, CIE, grade 2 hepatosteatosis, blepharitis, Jordan's anomaly, and lipid accumulation in frozen skin biopsy detected in her 17-year-old brother. Genetic analysis confirmed a homozygous mutation in the ABHD5 gene [ABHD5, NM_016006, c. 594dupC p.(Arg199GInfs*11) rs387906335] in all siblings. The patient was young and in fertile ages and did not accept acitretin treatment. Therefore, we recommended regular use of emollients and a diet which was low in long-chain fatty acids (minimal saturated fat) and enriched with medium-chain fatty acids.{Figure 2}{Figure 3}

In the sixth month of the follow-up, the majority of the lower extremities returned to normal-looking skin, although the patient had not yet begun a diet. She stated that this change occurred as the weather got warmer [Figure 1]c. The second biopsy performed from the transient, apparently intact area showed no substantial difference, except for the thinner keratin layer measured by ocular micrometry as 50 μm and 25–30 μm in the first and second biopsies, respectively [Figure 4].{Figure 4}


NLSDI is caused by mutations in the ABHD5 gene located in chromosome-3.[3] The ABHD5 gene produces a protein involved in fat metabolism called CGI-58. This protein helps the activity of the main enzyme, which is adipose TG lipase. When the TG cannot be broken down, it accumulates in various parts of the body as lipid droplets and causes different symptoms. Accumulation of lipid is related to dry, scaly skin at birth, as well as progressive hepatosteatosis and various degrees of muscular involvement, ophthalmologic problems, hearing loss, mild intellectual disability, etc.[4]

Although nonbullous CIE is the commonly seen form of ichthyosis in NLSDI, rarely different forms of ichthyosis have been reported, such as nonspecific ichthyosiform dermatosis or even nonerythrodermic ichthyosis. In a few cases, a presentation with normal-looking skin islets in different body parts as well as widespread erythema and desquamation has also been reported.[2],[5],[6] This phenomenon was also described by Pujol et al.[2] as erythrokeratodermia variabilis-like ichthyosis and by Singh et al.[5] as progressive symmetric erythrokeratodermia-like features in NLSDI. In the follow-up, differently from the literature, we found that these normal-looking skin islets on the lower extremities were covered entirely with erythema and ichthyosis that fit in CIE clinic.

Since these normal-looking skin areas always appear in the same area, we initially thought that there might be a relatively high level of enzyme or helper protein activity in keratinocytes of these areas due to differences in ABHD5 mutations or additional unidentified mutations, but this hypothesis was not supported by the fact that lipid vacuoles were roughly in similar distribution and number in the second biopsy. No biopsy from normal-appearing skin was taken to compare findings with the lesional area in the other studies in the literature. We found that the keratin layer thickness was almost halved on normal-looking skin. Ujihara et al.[6] and Pujol et al.[2] reported that skin findings were aggravated with temperature elevation. Unlike these two studies, in our case, the severity of skin findings decreased with increasing temperature [Table 1]. Mieremet et al.[7] compared at a range of 33–37°C the epidermal maturation in full-thickness skin models in vitro. Their results showed that keratin layer thickness decreases with culture temperature rising to 37°C. This indicates that the ambient temperature plays an important role in epidermal morphogenesis. Low temperature and low humidity have also been shown to cause an overall decrease in the function of the skin barrier.[8]{Table 1}

Another important aspect of our case report is that frozen tissue examination played a key role in the diagnostic workup. In the routine histopathological examination of a skin biopsy in NLSDI, the lipid accumulation appears as empty vacuoles that can be easily overlooked. A PubMed search was done for “neutral lipid storage disease and biopsy” and “Chanarin–Dorfman and biopsy”, and we found that frozen section examination was used in only five reports.[4],[5],[6],[9],[10] We recommend frozen examination instead of routine histopathological examination in order not to miss the diagnosis, in all nonbullous CIE patients, not only in NLSDI.

In conclusion, patches of normal-looking skin, “islets of sparing” may be an important clue to distinguish NLSDI from other diseases in the spectrum. We consider that this phenomenon is not associated with a different type of ichthyosis than nonbullous CIE in NLSDI, as it was limited to a particular region, disappeared completely, and was a finding that emerged years later. In order not to miss the diagnosis, we also recommend performing peripheral blood smear on all nonbullous CIE patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given her consent for images and other clinical information to be reported in the journal. The guardian understands that her names and initials will not be published and due efforts will be made to conceal the patient's identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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