|Year : 2015 | Volume
| Issue : 1 | Page : 39-41
Ichthyosis follicularis alopecia and photophobia syndrome:Transient improvement with oral isotretinoin
Sandhya Chauhan1, Pratik Gahalaut2, Kalpana Chandra3
1 Department of Pediatrics, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, Uttar Pradesh, India
2 Department of Dermatology, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, Uttar Pradesh, India
3 Department of Pathology, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, Uttar Pradesh, India
|Date of Web Publication||16-Jan-2015|
69, Silver Estate, PO RKU, Bareilly 243 006, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Ichthyosis follicularis alopecia photophobia (IFAP) syndrome (OMIM 308205) is a rare genetic disorder characterized by a triad of follicular ichthyosis, congenital atrichia of scalp and photophobia. Until date, only 40 patients have been mentioned in the worldwide literature. The management of this syndrome remains a daunting task because very few case reports have described interventions for treating various clinical features of this entity. We describe IFAP syndrome in an 18-month-old male child, who showed transient improvement in his cutaneous features with oral isotretinoin therapy.
Keywords: Congenital atrichia, follicular plugging, ichthyosis, photophobia, retinoids
|How to cite this article:|
Chauhan S, Gahalaut P, Chandra K. Ichthyosis follicularis alopecia and photophobia syndrome:Transient improvement with oral isotretinoin. Indian J Paediatr Dermatol 2015;16:39-41
|How to cite this URL:|
Chauhan S, Gahalaut P, Chandra K. Ichthyosis follicularis alopecia and photophobia syndrome:Transient improvement with oral isotretinoin. Indian J Paediatr Dermatol [serial online] 2015 [cited 2020 Jan 26];16:39-41. Available from: http://www.ijpd.in/text.asp?2015/16/1/39/149429
| Introduction|| |
Ichthyosis follicularis alopecia photophobia (IFAP) syndrome (OMIM 308205) is a rare genetic disorder characterized by a triad of follicular ichthyosis, congenital atrichia of scalp and photophobia.  Till date, only 40 patients have been reported worldwide.  Effective management of this case is a challenging task with very few reports detailing the therapeutic options.  We report a case of IFAP syndrome with a favorable response to a short course of isotretinoin.
| Case report|| |
An 18-month-old male child presented in the pediatric department with a history of dry skin, atrichia, global developmental delay, seizures, frequent regurgitations and recurrent respiratory tract infections since birth. Child was borne of a nonconsanguineous marriage at term after normal pregnancy by vaginal delivery. He was third in order with the healthy 6-year-old sister and second sister who died immediately after birth due to unknown reasons. Mother denied any history suggestive of collodion membrane at birth. Child started developing tonic-clonic seizures by 6 months of age. He developed eye contact and started holding his head at 6 months of age. He started sitting at 12 months of age. He was operated for right-sided inguinal hernia at the age of 11 months. At presentation, he was unable to speak monosyllables.
On physical examination, weight was 7 kg, length was 68 cm and head circumference was 39 cm (all <3 rd percentile for age). He had a prominent forehead with large ears [Figure 1]. Cutaneous examination revealed nonscarring alopecia over the scalp and eyebrows. Skin over the abdomen was rough in texture due to multiple, spiny, uniformly distributed, white follicular projections [Figure 2]. Skin over the scalp, face and shin had irregular icthyotic patches. Palms, soles, dentition, oral cavity, genitalia and nails appeared normal. Ophthalmic examination was normal except marked photophobia. Routine hematological and biochemical investigations were normal. Skeletal survey, electrocardiogram, ultrasonography of the abdomen, brainstem evoked auditory response failed to reveal any abnormality. Computed tomography scan head revealed evidence of subtle loss of the right occipital and parietal subcortical white matter. Skin biopsy [Figure 3] showed hyperkeratosis in epidermis along with keratotic follicular plugging and thin granular layer. No evidence of scarring alopecia was evident in biopsy. Gene mutational analysis was not done due to financial constraints.
|Figure 1: Generalized alopecia along with ichthyotic, scaly patches over face and scalp|
Click here to view
|Figure 3: Hematoxylin and eosin stain shows keratotic follicular plugging along with thin granular layer (×40)|
Click here to view
Diagnosis of IFAP syndrome was made on the basis of characteristic cutaneous features, non-scarring atrichia, photophobia and supportive histopathologic picture. This was corroborated by histopathological findings. Topical application of soft and light liquid paraffin along with urea and lactic acid combination proved futile. Oral isotretinoin was started at 0.2 mg/kg/day and gradually increased to 0.5 mg/kg/day over 1-month. He remained on isotretinoin for 4 months and received 275 mg of isotretinoin in total, which resulted in marked improvement in cutaneous lesions. However, there was no improvement in photophobia. Child had no major side-effects and monitoring was done with monthly lipid levels, complete blood counts and liver function tests. He was also started on sodium valproate 20 mg/kg/day with cessation of seizures. Isotretinoin was withdrawn as his skin texture improved. Unfortunately, the rough texture of the skin along with follicular projections recurred on withdrawing isotretinoin, and he was lost to follow-up.
| Discussion|| |
Patients with IFAP syndrome share a unique, characteristic appearance with total alopecia, severe photophobia and generalized "thorn-like" projections on the skin.  The diagnosis of IFAP is based on the presence of a missense mutation in MBTPS2 gene and characteristic clinical appearance.  Relative rarity of this syndrome and nonaccessibility of mutational analysis, like in our case, makes the diagnosis difficult. Though IFAP syndrome has a recessive X-linked pattern of inheritance, autosomal mode of inheritance has also been reported. 
In IFAP syndrome, characteristic cutaneous manifestations consist of follicular keratotic spiny papules distributed symmetrically over scalp and extensor aspect of extremities along with congenital noncicatricial alopecia involving the scalp, eyebrows and eyelashes.  The spine imparts a peculiar sensation on palpation, which has been described as resembling a "nutmeg grater" or "the prickly surface of a roseleaf".  Skin histopathology is nonspecific. Though abortive sebaceous glands are present in hair follicles, the total number of hair follicles are not significantly decreased.  Psoriasiform plaques, cheilitis, hypohidrosis, dystrophic nails, atopic manifestations, inguinal hernia may occur in up to 40% of patients.  Photophobia, superficial corneal ulcerations, progressive corneal vascularization, chronic tearing, cataract, astigmatism and even loss of vision have been reported.  Intellectual disability, seizures, hypotonia, short stature, frontal bossing, large ears, choanal atresia, recurrent infections and intestinal anomalies may be other findings.  Neurological features consist of olivo-cerebellar atrophy, malformation of the temporal lobes, mild inner cerebral atrophy, pseudobulbar paresis, hypoplasia of the corpus callosum, micro and turricephaly. , Nonnutritional rickets, allergic asthma, rhinoconjunctivitis, anaphylactic and urticarial reactions have been described in a few cases. 
Several differential diagnosis of concurrent ichthyosis and alopecia were excluded in our case. Notable among these were dermotrichic syndrome, keratitis-ichthyosis-deafness syndrome (KID), keratosis follicularis spinulosa decalvans (KFSD) and hereditary mucoepithelial dysplasia (HMD). Dermotrichic syndrome was ruled out due to the absence of nail and/or intestinal anomalies. , Absence of palmoplantar keratoderma, hearing loss and small/malformed teeth excluded KID syndrome.  KFSD has noncongenital, scarring and progressive alopecia, unlike our case. , IFAP was differentiated from HMD by the absence of the perineal rash and eryhthematous plaques/papules in the oral mucosa. 
Management of the several features in this syndrome remains a daunting task. Follicular hyperkeratosis can be effectively managed by topical corticosteroids, tretinoin and urea containing creams. In refractory cases, oral acitretin resulted in partial improvement of cutaneous features in patients.  In our case, oral isotretinoin resulted in transient improvement in cutaneous features without any effect on photophobia and developmental delay. Earlier, in one case, oral vitamin A 250,000 IU/day administered for 6 months led to improvement in photophobia and softer texture of the skin.  Seizures require antiepileptic therapy and our patient responded favorably to valproate.  Inguinal hernia may resolve spontaneously.  Likewise, seizures may resolve spontaneously later in life.  Life expectancy in patients with IFAP syndrome can vary from death in the neonatal period to normal survival. 
To summarize, this unique oculo-cutaneous disorder requires further characterization. , In the search of a better therapy, treatment in every case of IFAP syndrome, requires proper documentation so that an acceptable and effective management of this entity may be possible in the future.
| References|| |
Mégarbané H, Mégarbané A. Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome. Orphanet J Rare Dis 2011;6:29.
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.
Eramo LR, Esterly NB, Zieserl EJ, Stock EL, Herrmann J. Ichthyosis follicularis with alopecia and photophobia. Arch Dermatol 1985;121:1167-74.
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.
Kamo M, Ohyama M, Kosaki K, Amagai M, Ebihara T, Nakayama J, et al.
Ichthyosis follicularis, alopecia, and photophobia syndrome: A case report and a pathological insight into pilosebaceous anomaly. Am J Dermatopathol 2011;33:403-6.
Bibas-Bonet H, Fauze R, Boente MC, Coronel AM, Asial R. IFAP syndrome "plus" seizures, mental retardation, and callosal hypoplasia. Pediatr Neurol 2001;24:228-31.
Martino F, D'Eufemia P, Pergola MS, Finocchiaro R, Celli M, Giampà G, et al.
Child with manifestations of dermotrichic syndrome and ichthyosis follicularis- alopecia- photophobia (IFAP) syndrome. Am J Med Genet 1992;44:233-6.
Rai VM, Shenoi SD. Ichthyosis follicularis with alopecia and photophobia (IFAP) syndrome. Indian J Dermatol Venereol Leprol 2006;72:136-8.
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.
Keyvani K, Paulus W, Traupe H, Kiesewetter F, Cursiefen C, Huk W, et al.
Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome: Clinical and neuropathological observations in a 33-year-old man. Am J Med Genet 1998;78:371-7.
[Figure 1], [Figure 2], [Figure 3]