Dr.Venkatesh Kumar M, Dr.C.Jayakumar, Dr.Praveena, Dr.Preethi, AIMS,Kochi.
Twenty five days old female ba (Late Preterm- 35 weeks + 5 days) 1st child of NCM presented with the complaints of pustular skin lesions since birth which used to subside with medications parenteral IV Antibiotics to recur again. Initially mother noticed the lesions in the form of erythematous, raised , non itchy lesions on the trunk then progressed to involve upper and lower limbs.Lesions recurred on day 11 of life, for which the ba was admitted again and treated with multiple antibiotics.
Antenatal Mother had uteroplacental insufficency ,IUGR, TORCH panel – CMV IgG :reactive (262), 4 doses of Inj.Betamethasone was received the mother
Natal : Preterm(35 weeks + 5 days)
Birth wt: 2.030kg/LSCS (Ind:Fetal distress, IUGR)/CIAB
Postnatal : Ba was shifted to NICU in view of respiratory distress soon after birth and was started on nasal oxygen .Body had pustular lesions over trunk, limbs at birth, following which Sepsis panel was sent and ba was started on Inj. Crystalline penicillin which was then hiked to Inj. Piptaz . lesions subsides and reccur again. Pustular lesions recurred after 2 days- ? vesicular ? pustular lesion more on extremities than trunk ina linear fashion
Hep-B and Vit-K given at birth, Birth dose of BCG and OPV is pending. History of similar fluid filled skin lesions in the mother soon after birth present till 3 months of age was told the mother
On examination,vitals were stable. Auxology revealed weight and length below third centile. Head to foot examination revealed multiple discrete and grouped pustules on B/L Upper and lower limbs- mainly over left UL and LL – ?Blasckoidal distribution, Skin lesions heal without any scar . Systemic examination was within normal limits.
DIfferentials considered at this point were:
1. Immunodeficency disorders
2. Incontinentia pigmenti
3. Epidermolysis bullosa
4. Neonatal candidiasis
5. Bacterial folliculitis
Investigations:
Hemogram: TC- 22.8 K/uL, N- 7%, L-40%, E- 43%( severe eosinophilia), Hb-15.6 gm/dl, Plt- 5.28 lakh, CRP – 0.10 mg/L.
LFT , RFT, Serum electrolytes – Normal.
Peripheral blood smear: Leucocytosis with severe Eosinophilia .
Immunoglobulin profile (Ig – G,A,M,E)- Within normal limits for the corresponding age limits.
Hematology consult availed and advised Lactate- 3.67 mmol/L , Bicarbonate – 16.8 mmol/L, Pyruvate- 0.7 mg/dl , RBS- 89.1 mg/dl ( organic acidemias ruled out).
TORCH IgM – Negative.
Chest Xray: Normal.
USG Abdomen- Trace prominence of B/L collecting system.
Skin Biopsy- Histopathology: – Epidermis shows rete pegs with thin granular layer and basket weave keratin. There is spongiosis with moderate exocytosis of eosinophils and spongiotic vesicles containing eosinophils. Eosinophil tagging seen along basal layer. The dermis is hyalinised edematous and upper dermis shows perivascular and interstitial infiltrate of eosinophils, lymphocytes and histiocytes.
Impression : Morphological possibility is that of Incontinentia pigmenti.
Genetic consultation was availed and WES sent.
VEEG: did not reveal any epileptiform abnormalities, no events recorded.
Ophthalmology consultation :
Dilated fundus-
Right eye: Disc & macula -normal, fully vascularised and thin strips remains.
Left eye: Disc is Hyperemic, vessels tortuous at posterior pole, macula partially vascularised , Rest of the retina is vacularised upto zone 2 , posterior looping of vessels ? New vessels. No ROP features.
Impression: ? Incontinentia Pigmentia retinopathy of Left eye.
Following which Left eye intra vitreal Implantation of ranibizumab (1) was given under topical anesthesia.
Post Anti-VEGF injection –
Left eye: Zone 2 – partially vascularised, regression of neovascularisation, No ridge seen. Right Eye: Disc and macula appears normal.
Ba was given Inj.Cefadroxil, Topical Mupirocin and multivitamin supplements.
Diagnosis: INCONTINENTIA PIGMENTI WITH RETINOPATHY CHANGES IN THE LEFT EYE.
Discussion:
Incontinentia pigmenti (also known as Bloch-Sulzberger syndrome is an X-linked dominant genodermatosis that is usually lethal in males before birth . IP is caused loss-of-function mutations in the IKBKG (inhibitor of kappa light polypeptide gene enhancer in B cells, kinase gamma) gene, formerly known as NEMO (nuclear factor-kappa-B essential modulator), encoding a regulatory protein named IKK (NEMO) that activates genes involved in cell survival, inflammation, and immunity.
In females, IP typically presents with a staged, linear, cutaneous eruption and often with anomalies of the teeth, hair, nails, and retina . Approximately one-third of patients have ocular and neurologic abnormalities. Because of the involvement of skin, hair, nails, and teeth, IP can be considered a form of ectodermal dysplasia.
· Diagnosis is established clinically presence of > 1 major criteria which consists of skin lesions that occur in stages from birth to adulthood
· bullous stage – characterized erythema followed vesicobullous eruptions that typically present at age 6-8 weeks but may be present at birth
· verrucous stage – characterized warty papules and keratotic patches that typically present in first few weeks or months of life and disappear age 6 months
· hyperpigmented stage – characterized swirling or whirling macular patches of hyperpigmentation that typically present anywhere between infancy and adolescence, but mostly fades early adulthood
· hypopigmented/atretic stage – characterized patchy areas of hypopigmentation that are mainly arranged in streaks or whorls that typically present during adolescence and persists into adulthood (may be permanent)
minor criteria support the diagnosis and include
· hypodontia or anodontia, microdontia, abnormally shaped teeth
· alopecia or woolly hair
· mild ridging or pitting of nails; onychogryposis
· peripheral neovascularization
· family history consistent with X-linked inheritance or a history of multiple miscarriages of male fetuses
· seizures, intellectual disability
· typical skin histologic findings (eosinophilic infiltration and/or extracellular melanin granules)
· supernumerary nipples and breast aplasia
· cleft palate and high arched palate
· If clinical features are inconclusive, genetic testing can be used to confirm diagnosis.
· Treatment:
· Multidisciplinary team to help establish the extent of the disease and address ongoing needs
· Medications such as antivascular endothelial growth factor, topical tacrolimus, and dexamethasone for the treatment of some of the eye, skin, and neural manifestations, respectively
· Surgeries and procedures such as laser photocoagulation or cryotherapy and pars plana vitrectomy for certain ocular manifestations
· Close follow-up for incontinentia pigmenti patients to monitor for complications .
Carry home message:
Babies presenting multiple vesiculobullous lesions should not always only be worked up for immunodeficiency disorders.Extensive workup involving Dermatolgy, Ophthalmology can pick up conditions like Incontinentia pigmenti with its complications ,which can be treated early improving the prognosis of the condition.