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Year : 2022  |  Volume : 14  |  Issue : 6  |  Page : 213-215  

Ichthyosis follicularis with alopecia and photophobia syndrome with coexisting palmoplantar keratoderma treated with acitretin

Department of Dermatology, Venerology and Leprosy, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Date of Submission14-Jan-2022
Date of Acceptance14-Jun-2022
Date of Web Publication31-Jan-2023

Correspondence Address:
Eswari Loganathan
Department of Dermatology, Venerology and Leprosy, Bangalore Medical College and Research Institute, Bengaluru - 560 002, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijt.ijt_9_22

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Ichthyosis follicularis with alopecia and photophobia (IFAP) syndrome is a rare congenital genetic disorder characterized clinically by a triad of follicular ichthyosis, alopecia and photophobia. The genetic inheritance pattern in IFAP syndrome is said to be X-linked with mutations of the membrane-bound transcription factor peptidase, site 2 gene. Histopathology of the skin shows dilated hair follicles with keratin plugs extending above the surface of the skin. In this case report, we describe a 6-year-old girl with clinical features of IFAP along with palmoplantar keratoderma. Skin biopsy was done to confirm the diagnosis after which she was started on acitretin (10 mg per day). Good improvement in cutaneous features was observed after 1 month.

Keywords: Acitretin, ichthyosis follicularis, Ichthyosis Follicularis with Alopecia and Photophobia syndrome

How to cite this article:
Rajesh S, Loganathan E, Shanmukhappa AG. Ichthyosis follicularis with alopecia and photophobia syndrome with coexisting palmoplantar keratoderma treated with acitretin. Int J Trichol 2022;14:213-5

How to cite this URL:
Rajesh S, Loganathan E, Shanmukhappa AG. Ichthyosis follicularis with alopecia and photophobia syndrome with coexisting palmoplantar keratoderma treated with acitretin. Int J Trichol [serial online] 2022 [cited 2023 Jun 10];14:213-5. Available from: https://www.ijtrichology.com/text.asp?2022/14/6/213/368910

   Introduction Top

Ichthyosis Follicularis with Alopecia and Photophobia (IFAP) syndrome is a rare X-linked genetic disorder identified by a clinical triad of follicular ichthyosis, alopecia, and photophobia.[1] It is said to be caused due to missense mutations of membrane-bound transcription factor protease, site 2 which is an intramembrane zinc metalloprotease. IFAP syndrome is associated with an abbreviated function of this chief regulatory system, modifying cholesterol and endoplasmic reticulum homeostasis.[2] It is a rare disorder with only 11 cases reported from India up to 2021.[3] We report IFAP syndrome in a female patient with an additional feature of palmoplantar keratoderma (PPK).

   Case Report Top

A 6-year-old female child was brought to our dermatology outpatient department with complaints of generalized dryness of skin with multiple raised lesions all over the body, including the head from 6 months of age. This was associated with loss of hair and watering of eyes when exposed to the sunlight. She had normal growth and developmental milestones. The child was born out of third-degree consanguineous marriage and is the eldest of three children. Her siblings do not have similar features.

On clinical examination, we observed multiple, discrete, skin-colored, follicular oriented hyperkeratotic spiny papules over the extensor aspect of bilateral upper limbs, bilateral lower limbs, shoulders, face, and scalp. Terminal hair was absent on the scalp, eyebrows, and eyelashes [Figure 1]a. There were yellowish, thick, hyperkeratotic plaques surrounded by erythema over the heel and head of metatarsals of both the feet [Figure 1]b.
Figure 1: (a) Alopecia seen as absence of terminal hair on the scalp and eyebrows (b) Plantar keratoderma seen as yellowish, thick, hyperkeratotic plaques on both the feet

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Trichoscopic examination at ×10 magnification using DermLite DL4 dermascope showed follicular ostia covered with a keratin plug. Few vellus hair is present [Figure 2]. Skin biopsy was done, and it showed an atrophic epidermis. Follicles appeared dilated with keratin plugging. There was a decrease in sebaceous glands, along with hyperplasia of arrector pili muscle [Figure 3]. The hematological examination was normal.
Figure 2: Trichoscopy showed keratin plug covering follicular ostia (blue circle) and presence of few vellus (red arrow) (×10)

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Figure 3: Histopathology section showed dilated follicular orifice with keratin plugging (10×)

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Given the history, the presence of alopecia and follicular ichthyosis on cutaneous examination, presence of photophobia and characteristic histopathological features, the diagnosis of IFAP syndrome was made.

The patient was advised frequent and regular use of emollients and started on T. acitretin 10 mg OD, significant improvement in the cutaneous features was noticed at the follow-up visit after 2 months [Figure 4].
Figure 4: (a) Spiny papules on the leg at presentation, (b) Improvement in the skin lesions noted after 2 months of taking T. acitretin

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   Discussion Top

Patients with IFAP have generalized cutaneous “thorn-like” projections that confer a distinctive sensation on palpation.[4] To date, the majority of patients reported under the name of IFAP syndrome have been males. Cambiaghi et al. described IFAP syndrome in two unrelated female patients suggesting that X-linked pattern of inheritance is not always the rule and a different way of transmission or the genetic heterogeneity of IFAP syndrome has to be considered.[5] Photophobia is an essential feature for the diagnosis of IFAP, with the inevitable progression of corneal vascularization and loss of vision in males with this syndrome. Retinal vascular tortuosity may be a clinical sign of carrier status in females.[1]

The major differential diagnosis for a case of IFAP syndrome is keratosis follicularis spinulosa decalvans (KFSD), which is characterized by progressive scarring alopecia.[6] Alshami et al. reported a case of IFAP in a male child with hyperkeratosis over the sole, similar to our case, therefore adding to the literature that has shown an association of PPK with classical IFAP syndrome, suggesting a new entity IFAP-PPK syndrome.[7]

Management of this is a challenging task with the main component being regular use of emollients. Khandpur et al. reported moderate response to acitretin therapy (1 mg/kg) when it was administered for 6 months, with significant flattening of the follicular keratotic papules and hyperkeratotic plaques.[8] We observed a significant improvement in the follicular keratinization defect when our patient was treated with acitretin, but there was no change in the status of alopecia. The patient did not develop major side-effects and monthly monitoring of complete blood count, liver function tests and lipid levels were done.

We report this rare congenital syndrome to raise awareness of possible associations that may coexist with it. There is a need for better therapy that will alleviate the hair abnormalities of this entity so that effective management may be possible in the future.

Declaration of patient consent

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

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Conflicts of interest

There are no conflicts of interest.

   References Top

Mégarbané H, Mégarbané A. Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome. Orphanet J Rare Dis 2011;6:29.  Back to cited text no. 1
Oeffner F, Fischer G, Happle R, König A, Betz RC, Bornholdt D, et al. IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response. Am J Hum Genet 2009;84:459-67.  Back to cited text no. 2
Bains A, Vedant D, Verma A, Bhardwaj A, Nalwa A. Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome: A case report and review of cases reported from India. Indian Dermatol Online J 2019;10:686-91.  Back to cited text no. 3
[PUBMED]  [Full text]  
Rai VM, Shenoi SD. Ichthyosis follicularis with congenital atrichia, nail dystrophy and palmoplantar keratoderma. Variant of IFAP syndrome or a new entity? Dermatol Online J 2005;11:36.  Back to cited text no. 4
Cambiaghi S, Barbareschi M, Tadini G. Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome in two unrelated female patients. J Am Acad Dermatol 2002;46:S156-8.  Back to cited text no. 5
Nagakeerthana S, Rangaraj M, Karthikeyan K. Ichthyosis follicularis, alopecia, and photophobia syndrome. Int J Trichology 2017;9:67-9.  Back to cited text no. 6
Alshami M, Bawazir MA, Atwan AA. Photoletter to the editor: A new variant of ichthyosis follicularis with alopecia and photophobia (IFAP) syndrome with coexisting psoriasiform lesions and palmoplantar keratoderma. IFAP-PPK syndrome? J Dermatol Case Rep 2011;5:14.  Back to cited text no. 7
Khandpur S, Bhat R, Ramam M. Ichthyosis follicularis, alopecia and photophobia (IFAP) syndrome treated with acitretin. J Eur Acad Dermatol Venereol 2005;19:759-62.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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