Bijadushti Janya Asthi Dhatu Kshaya with Special Reference to Progressive Pseudo-Rheumatoid Arthropathy (Dysplasia) of Childhood – A Case Report

Introduction

Ayurveda acknowledges the etiological role of Bijadushti (genetic defects) in various congenital deformities. Defective Bijabhaga and Bijabhagavayava (fractions of ova and sperm indicative of chromosomes and genes, respectively) are responsible for defective organogenesis and its inheritance.¹ Ayurveda also hints towards de novo mutations due to environmental factors such as faulty Ahara Vihara (diet and lifestyle) causing Vikriti (anatomical, physiological and chromosomal deformities) in Garbha (foetus).² Besides, Vata (Dosha responsible for movement and cognition) vitiation in pregnant mother is implicated for deformities like Pangutva (lameness), Kubjatva (hunchback/ kyphosis) and Vamanatva (dwarfism/ short stature).³

Progressive pseudo-rheumatoid arthropathy (dysplasia) of childhood (PPAC; PPD) is an autosomal recessive condition caused by mutation in the WISP3 (WNT1- inducible signalling pathway protein 3) gene located at 6q 22-6q 23.⁴ The WISP3 gene regulates the expression of type II collagen and aggrecan in chondrocytes. Gene is essential for normal post-natal skeletal growth and cartilage homeostasis.⁵ Arthropathy becomes clinically evident in early childhood with persistent degeneration of articular cartilage causing joint enlargement, stiffness, pain on movement, fatigue, and limited range of motion. Osteoarthritis, osteoporosis, and contractures develop over time. Reduced joint space in hip and knee joints impairs walking capacity and gait. Spine deformities such as kyphosis and lordosis are evident. Hip pain is a common problem in adolescence. The height of the affected children is usually shorter than the normal children.

Ayurveda advocates many precautionary measures to prevent genetic disorders such as avoiding Tulyagotra Vivaha (consanguineous marriage), pre-conception Bijashuddhi (attaining flawless seed) by Panchakarma (five eternal bio-cleansing therapies). Also, not indulging in Garbhopaghatakara Bhava (factors endangering foetal health/life) and fulfilling Dauhrida (desires of a pregnant woman), is crucial for avoiding congenital anomalies. However, the limitation in managing genetic disorders is clearly expressed by Charaka, citing the Bijadushti as a cause for the incurability of such diseases.⁶

Understanding Bijadushti and affected Anga/ Angavayava (body part), Samprapti (pathogenesis), Upashaya-Anupashaya (favourable and unfavourable treatment and interventions) in the light of Ayurvedic Siddhanta is prerequisite for planning the management to provide symptomatic relief in such incurable diseases. Also, increasing awareness of PPAC; PPD is essential for a timely and accurate diagnosis, as its clinical presentation is very much similar to juvenile Amavata (~rheumatoid arthritis), leading to misdiagnosis of the condition. With these aims, this case report is being presented.

Case Presentation

A North Indian, 11.5 years old male child, born of non-consanguineous marriage with normal birth history, sought treatment for swelling and stiffness in hand joints and difficulty in sitting, walking, and maintaining posture for past seven years. The stiffness was maximum in the morning. Excessive use of the mobile phone in neck bent downwards position during the Corona pandemic aggravated neck stiffness, limiting its extension capacity. Parents were concerned about increasing joint deformities, abnormal posture, and difficulty in walking.

The growth and developmental history were normal till the age of three years. In the year 2013, swelling of joints with restricted movements were first noticed. After that, the growth (especially height) started lagging and difficulty in walking ensued. Initially, the condition was misdiagnosed and treated as Juvenile Rheumatoid Arthritis. PPAC; PPD was confirmed in November 2018. The parents were informed about the disease's incurable nature and were instructed to provide regular physiotherapy. A hip transplant surgery in the future was suggested. He discontinued physiotherapy during Covid pandemic and was on multivitamin supplements when he visited our hospital.

Clinical findings

The child was conscious and oriented. Mobility was limited to short walks without support, with severe waddling on plain surfaces and was climbing few steps with support. The child could cover 50 meters distance with severe waddling in two minutes. Overall walking capacity at a stretch before needing rest was 580 meters.

Dashavidhapariksha (~Ten-Fold Examination)

Prakriti, Vata Kaphaja, Vikriti of Vata and Shleshaka Kapha was present. Satva was Avara, and the child had Madhura Rasa Pradhana Sarva Rasa Satmya. He had features of Mamsa Sara in general, but the wasting of muscles associated with affected joints was present. Samhanana and Pramana, Vyayamashakti and Aharashakti were Avara.

Ashtavidha Pariksha (Eight-Fold examination)

Nadi was Vata dominant. Urine frequency was 4-5 times a day. Mala was Nirama. Jihwa was Alipta. He had Anushna Sparsha and normal Shabda. His Drishti was normal. Akriti was Hina.

Samprapti Ghataka (Etiopathogenesis)

Dosha : Vata, Kapha

Dushya : Mamsa, Asthi

Agni : Jatharagni and Dhatwagni Mandya

Ama : Jatharagni and Dhatwagni Mandya Janya Ama

Srotas : Asthivaha, Mamsavaha

Sroto Dushti : Sanga

Udhbava Sthana : Amashaya

Sanchara Sthana : Asthivahi Srotasa

Vyakta Sthana : Asthi

Adhistana : Sandhi

Roga Marga : Madhyama

Sadhya Asadhyata : Asadhya

Swabhava : Chirakari

General examination

Vitals were normal and respiratory, cardiovascular, and central nervous systems did not show any abnormality. Bhramari (humming bee breathing) time was 10 seconds. Weight was 31.5 kgs (25th percentile of the normal weight for that age). His height was 131 cm (below the 3rd percentile for his age), and BMI was 17.3 kg/m2. Pallor, icterus, cyanosis, clubbing, and lymphadenopathy were absent.

Joint examination

Interphalangeal joints enlargement with flexion deformity with tenderness in joints on pressing and pain on attempted movement were present (Visual Analogue Scale Score - 3) (Figure 1) (Figure 2). Erythema was absent and the temperature of the affected joints was normal. Wasting of the intrinsic, thenar and hypothenar muscles was present bilaterally (Figure 3). Both knee joints were enlarged, and calf muscle wasting was present (Figure 4). Both active and passive ranges of motion (ROM) were reduced in most of the joints barring the shoulder joint. Mild scoliosis and lumber lordosis were present.

Diagnostic assessment

With the findings of negative Antinuclear Antibody Test (ANA), normal Antistreptolysin O (ASO) titre (753 IU/ mL), negative Rheumatoid (RA) factor (<11.4 IU/mL), normal ESR (10 mm/hr), the child was misdiagnosed and treated for seronegative Juvenile Rheumatoid Arthritis (JRA) for an unspecified period. 

In November 2018, a DNA test identified compound heterozygous variants in WISP 3 gene confirming the diagnosis of PPAC; PPD.

Past treatment history

Naproxen (NSAID), DFZ (Deflazecort), Saaz (sulfasalazine), Methotrexate, and Prednisolone were prescribed for an unspecified period for suspected Juvenile Rheumatoid Arthritis before 2016. He underwent irregular sessions of physiotherapy after the confirmation of diagnosis.

Therapeutic interventions

Amapachana, Agnideepana, Asthidhatu Vardhana and Rasayana, Sarvanga Abhyanga, Nadi Sweda and Matra Basti were given. The diet of the child comprised Madhura, Snigdha, Laghu, and Ushna food articles. Sukshma Vyayama (gentle exercises covering simple, gentle joint movements synchronized with breathing) to provide range of motion (ROM), Pranayama and Dhyana (meditation) were part of the routine.

Outcome and Follow-up (Table 2, 3)

There was good improvement in appetite, sleep, stamina, and pain. ROM in most of the joints was unchanged, barring wrist joints. Walking capacity improved and climbing stairs became easier for the patient. The patient was advised to continue oral medication for another three months and Sukshma Vyayama every day.

Discussion

In PPAC;PPD, genetic mutation in WISP3 (WNT1- inducible signalling pathway protein 3) gene is responsible for Asthi dhatu Kshaya causing a condition of progressive arthropathy. It is noteworthy that Vata is responsible for the proper structure of the Garbha, and Vibhajana (division) and Gati (movement), the two crucial processes (occurring during passing over of parental genetic material) considered to be controlled by Vata according to Ayurveda.⁷ Thus, indulgence in Vata Vitiating Ahara Vihara by pregnant mother may result in Beejadushti. Charaka directly associates consumption of Vata vitiating diet to vitiation of Asthivahi Srotasa. ⁸ In a pregnant mother, the adverse effects of Vata vitiating Ahara-Vihara will reach the foetus as well and can cause deformities like Pangutva (lameness), Kubjatva (hunchback/ kyphosis) and Vamanatva (dwarfism/ short stature).⁹ The state of impaired Asthi Dhatu Nirmana (formation) and Poshana (nutrition) resulting in Asthi Dhatu Kshaya in PPAC;PPD implies that Dushti in Bijabhagavayava related to Asthi Vahi Srotasa (~channels of bone tissue) of the foetus may have resulted in Kha Vaigunya (~pathological changes) in the channels of Asthi Dhatu, also making them prone to Srotovarodha (obstruction), obstructing the smooth flow of Vata and entrapping it through the process of Marga Avarana.

According to Ayurveda, Vata vitiation can happen either due to Dhatu Kshaya or due to Marga Avarana (entrapment of Vata within the channels).¹⁰ Based on the etiopathogenesis of PPAC;PPD, persistent Asthi Dhatu Kshaya as well as Marga Avarana appears to play a role in Vata vitiation in the child. That’s why, the child who is symptom free at birth and remains so for many years, gradually starts showing various symptoms of vitiated Vata such as Sandhi Shotha (joint swelling), Sandhi Shoola (joint pain), Sandhi Sankoch (contractures) and complete destruction of joints. As the child grows, progressive Asthi Dhatu Kshaya further escalates Vata vitiation and complications like Khanjatva, Pangutva, Kubjatva appear.¹¹

The treatment was initiated with Panchakola Phanta to remove Srotovarodha by its Pachana (~digestive) quality) and stimulation of metabolism at Dhatvagni level by Deepana quality. Ashthiposhaka Vati, a preparation containing Kukkutanda Twak (~hen’s eggshell calx), Ashthishrinkhala (Cissus quadrangularis Linn.), and Laksha, a secretion of Kerria lecca (Kerr) was chosen based on Samanya Vishesha Siddhanta, for supplementation of Prithvi Mahabhuta to restore and heal Asthi Dhatu. ¹² Gandha Taila stabilises Ashthi dhatu, and pacifies Vata. ¹³ Sarvanga Abhyanga (~whole body therapeutic massage), Nadi Sweda, and Matra Basti pacify Vata, relieve symptoms like stiffness and pain, and strengthens muscles. Dashamula Kwatha Churna, Eranda Patra (Ricinus communis L.), Nirgundi Patra (Vitex negundo Linn.) was added during Nadi Swedana for their Vatahara property. Bahya Snehana in the form of Sarvanga Abhyanga is a therapy of choice for Asthigata Vata. ¹⁴ Mahamasha Taila and Mahanarayana Taila used for Sarvanga Abhyanga and Matra Basti, are specifically indicated for kyphosis.¹⁵ Both oils have excellent Vata pacifying and strengthening actions besides Rasayana action. Rasayana function at the level of Poshaka Rasa, Agni, and Srotas, supplement the tissues by continuous rejuvenation or replenishment.¹⁶ Vasa (Adhatoda vasica [L] Nees) was chosen as an oral supplement as it is an excellent Rasayana in the stage of Kshaya. ¹⁷ Due to limited mobility and contractures in various joints, Yogasana and Vyayama were impractical; hence a range of motion exercise (ROM) in the form of Sukshma Vyayama was given. Sukshma Vyayama is a gentle way of giving ROM exercises to joints exhibiting limited mobility. Rhythmic, slow, repetitive stretching movement for each joint was given till a point of resistance in ROM was felt, and the joint was kept in that position for about ten seconds. The patient was instructed to concentrate on his breathing during this. Daily, around half an hour of Sukshma Vyayama was practiced during the period of hospital stay and the patient was advised to continue it after discharge as a daily exercise regimen. These practices help in loosening the joints and strengthens muscles.¹⁸

With this treatment regimen, improvement in Vata symptoms, Agni Deepana, and an overall increase in Vyayama Samarthya were achieved. Marginal improvement in ROM in some joints was noticed. Although there was no change in waddling gait, the patient had stopped taking support while climbing stairs (a total of nine stairs).

Conclusion

Being a Bijadushti Janya Vyadhi, PPAC; PPD is incurable. However, Agnivardhana, Amapachana, Srotoshdhana, Dhatuposhana in the form of Rasayana chikitsa and Asthidhatu Vardhana can achieve symptomatic relief. Modified stretching exercises such as Sukshma Vyayama may increase the range of motion without putting much pressure on the joints.

Conflict of Interest

All authors declare that there is no conflict of interest in publication of the manuscript or an institution or product that is mentioned in the manuscript.

Acknowledgment

Authors acknowledge all the interns and therapists involved in the patient care.