progressive nodular histiocytosis ( pnh ) is a rare normolipemic macrophage disorder first described by taunton et al . , in 1978 .
it belongs to a subgroup of non - langerhans cell histiocytosis ( lchs ) , the juvenile xanthogranuloma ( jxg ) family , which includes xanthoma disseminatum ( xd ) , benign cephalic histiocytosis ( bch ) , multiple adult xanthogranuloma ( maxg ) and generalized eruptive histiocytosis ( geh ) . according to weitzman and jaffee ,
they present positive reaction to factor xiiia , cd68 , cd14 and negative reactions to cd1a and s-100 proteins .
these disorders are difficult to categorize , primarily because of the diverse pathological findings and due to overlapping clinical and microscopic features .
a 30-year - old gentleman presented to us with complaints of asymptomatic nodular skin lesions all over the body of 10 years duration . at the age of 20 years , he started developing few small skin - colored lesions on the bilateral peri - orbital areas .
these lesions continued to increase in size over time and few lesions became pedunculated especially over the calves .
along with the appearance of the cutaneous lesions , he also noticed a gradually progressive , bilateral painless loss of vision .
he did not complain of itching , watering , photophobia or discharge from the eyes .
he was diagnosed to have eale 's disease and underwent laser photocoagulation for the same .
he developed premature cataracts of the eyes and was treated with phacoemulsification and posterior capsular intraocular lens implantation in both eyes .
prior to presentation to us , he underwent intra - lesional steroid therapy using triamcinolone acetonide in the peri - orbital lesions with good response seen in smaller lesions but no effect on the larger lesions .
the lesions at other sites were removed using various modalities like cryotherapy , radiosurgery and surgical excision of the larger , troublesome lesions .
cutaneous examination revealed multiple , approximately 30 to 40 , yellowish to skin - colored , firm , non - tender papules and nodules ranging in diameter from 5 to 40 mm , over the face [ figure 1 ] , trunk , extremities , elbows , hands , palms and soles [ figure 2 ] in decreasing order of frequency .
these lesions were located almost symmetrically over the peri - orbital area , mostly over the outer canthi , but also over the lower eyelids , leading to ectropion .
the smaller lesions on the face were mounted on the skin , while the larger lesions on the calf area were pedunculated .
papular and nodular lesions on the face and eyelid large nodules seen over the elbows , hand and sole visual acuity at the time of presentation was 6/18(r ) and 6/60(l ) .
the clinical differential diagnoses considered at the time of presentation to us were multiple eruptive dermatofibromas , xanthoma disseminatum and pnh .
blood examination revealed hemoglobin of 10.5 gm / dl with a microcytic hypochromic blood picture , total leukocyte count of 7200/mm and a normal differential leukocyte count . fasting lipid profile , renal ,
total serum proteins and albumin were normal with no reversal of the a : g ratio .
a cellular tumor was seen centered in the dermis , composed of sheets of oval to spindle - shaped cells arranged haphazardly , in short fascicles and in a storiform pattern at places [ figures 3a - c ] .
the spindle cells had oval to elongated benign looking nuclei with vesicular chromatin and small nucleoli .
on immunohistochemistry the cells were positive for cd68 [ figure 4 ] but negative for s-100 , cd34 , cd21 , cd35 and hmb45 supporting a diagnosis of spindle cell histiocytic tumor .
dab chromogen 100 based on the history , clinical examination and histopathological correlation , his dermatological disorder was diagnosed as pnh .
he was started on tab imatinib 400 mg od and some of the lesions developed encrustation but it was stopped after 5 months as he continued to develop new lesions while on this drug .
second - line treatment with pazopanib ( 800 mg od ) was started after stopping tab imatinib , in lines of soft tissue sarcoma .
based at the age of the onset of the lesions , areas of the body involved , progression of disease , lab abnormality ( serum lipids ) , it is possible to differentiate pnh from other forms in the jxg family .
benign cephalic histiocytosis and jxg usually occur in early childhood , but jxg has also been reported in adults and the lesions have a tendency to resolve spontaneously over a period of time .
multiple adult xanthogranuloma is another important differential diagnosis of pnh which has similar features to jxg but occurs in adults .
xanthoma disseminatum was ruled out based on the absence of mucosal and systemic involvement and with normal lipid profile as it usually presents with hyperchylomicronemia and hypertriglyceridemia and diabetes insipidus .
since the accurate diagnosis of a specific disorder within the jxg subgroup is quite difficult , we made the diagnosis of pnh based on the history , presence of the typical skin lesions , progressive course and histopathological demonstration of spindle cells that were positive on immunohistochemistry for histiocyte marker , cd68 , but negative for s-100 .
non - langerhan 's cell histiocytosis disorders are difficult to diagnose and our case presents another clinical expression of this variable and confusing disorder . to our knowledge
this is the first case report of progressive nodular histiocytosis associated with eale 's disease .
 progressive nodular histiocytosis ( pnh ) is a rare normolipemic macrophage disorder and belongs to a subgroup of non - langerhans cell histiocytosis ( lchs ) which is characterized by a progressive course with no sign of spontaneous resolution but without systemic involvement . 
 we report a 30-year - old gentleman who presented with skin lesions all over the body associated with gradual bilateral painless loss of vision . on examination , 
 approximately 30 to 40 , skin - colored , firm , non - tender papules and nodules were noted over the body especially on the face and trunk . 
 a skin biopsy revealed a cellular tumor in the dermis composed of oval to spindle - shaped cells , positive for cd68 but negative for s-100 , cd34 , cd21 , cd35 and hmb45 , supporting a diagnosis of spindle cell histiocytic tumor . 
 ophthalmic examination revealed a generalized arteriolar attenuation in both eyes . 
 he received tab imatinib 400 mg od for 5 months followed by tab pazopanib 800 mg od for 4 months and both the drugs were stopped due to lack of any response in the skin lesions . 
 we report this case due to its rarity , characteristic clinical presentation , and its association with eale 's disease . 
 primary treatment remains surgical excision of bothersome lesions and optimal systemic treatment is still unknown . 
Introduction
Case Report
Investigations
Discussion